Covid

COVID Transmission
Modeling
COVID Transmission
Modeling
An Insight into Infectious Diseases
Mechanism
DM Basavarajaiah
B Narasimha Murthy
First edition published 2022
by CRC Press
6000 Broken Sound Parkway NW, Suite 300, Boca Raton, FL 33487-2742
and by CRC Press

4 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
CRC Press is an imprint of Taylor & Francis Group, LLC
© 2022 DM Basavarajaiah and B Narasimha Murthy
Reasonable efforts have been made to publish reliable data and information, but the author and publisher cannot
assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers
have attempted to trace the copyright holders of all material reproduced in this publication and apologize to copyright
holders if permission to publish in this form has not been obtained. If any copyright material has not been a cknowledged
please write and let us know so we may rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or
utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented, including
photocopying, microfilming, and recording, or in any information storage or retrieval system, without written
permission from the publishers.
For permission to photocopy or use material electronically from this work, access www.copyright.com or contact the
Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. For works that are
not available on CCC please contact mpkbookspermissions@tandf.co.uk
Trademark notice: Product or corporate names may be trademarks or registered trademarks and are used only for
identification and explanation without intent to infringe.
Library of Congress Cataloging‑in‑Publication Data

Names: Basavarajaiah, DM, author. | Murthy, B. Narasimha, author.
Title: COVID transmission modeling : an insight into infectious diseases mechanism /
DM Basavarajaiah, B. Narasimha Murthy.
Description: First edition. | Boca Raton : Chapman & Hall\CRC Press, 2022. |
Includes bibliographical references and index. |
Summary: “This book will explore and formulate new mathematical/statistical and epidemiological modelling based
on the research findings. It covers all the aspects of mitigation, estimation of transmission rate, control measures,
economic impact assessment, genetic complexity of COVID and herd immunity”—Provided by publisher.
Identifiers: LCCN 2021058806 (print) | LCCN 2021058807 (ebook) |
ISBN 9781032069708 (hardback) | ISBN 9781032069746 (paperback) | ISBN 9781003204794 (ebook)
Subjects: LCSH: COVID-19 (Disease)—Transmission. | Coronavirus infections—Prevention. |
COVID-19 (Disease)—Economic aspects.
Classification: LCC RA644.C67 B365 2022 (print) | LCC RA644.C67 (ebook) |
DDC 362.1962/414—dc23/eng/20220121
LC record available at https://lccn.loc.gov/2021058806
LC ebook record available at https://lccn.loc.gov/2021058807
ISBN: 9781032069708 (hbk)

ISBN: 9781032069746 (pbk)
ISBN: 9781003204794 (ebk)
DOI: 10.1201/9781003204794
Typeset in Palatino
by codeMantra
Dedicated to
All victims of Novel Coronavirus 2019

Contents
Preface..............................................................................................................................................xv
Acknowledgments...................................................................................................................... xvii
Authors.......................................................................................................................................... xix
1. Mathematical Modeling Approach to COVID-19: Vetted Real Data........................... 1

1.1 Introduction....................................................................................................................1
1.1.1 Main Objectives of This Book.........................................................................3
1.2 Anatomical Structure of COVID-19 Virus................................................................ 10
1.3 Virus Incubation Period.............................................................................................. 11
1.3.1 Disease Carriers.............................................................................................. 12
1.3.2 Case Fatality Rate (CFR, %)........................................................................... 14
1.3.3 COVID-19 Transmission Mechanisms......................................................... 15
1.4 Epidemiological Aspects of nCov2019 (SARS-Cov-19)........................................... 15
1.5 Economic Impacts of Novel Coronavirus................................................................. 17
1.6 Mathematical Model for the Prediction of Novel Coronavirus (nCov2019)........ 18
1.6.1 Variables Used for Model Building.............................................................. 19
1.6.2 Endemic and Epidemic Equilibria............................................................... 21
1.7 Model Discussion......................................................................................................... 25
1.7.1 Model Conclusions......................................................................................... 26
1.8 Epidemiological Model for the Estimation of Hazard Rate and Geometric
Progression of nCov2019�� 27
1.8.1 Formulation of the Epidemiological Risk Assessment COVID Model.....28
1.9 Epidemiological Model Approach of New Diseases.............................................. 36
1.9.1 Model Formulation......................................................................................... 37
1.9.1.1
Latent growth model of novel coronavirus�� 38
1.9.2 Gauss–Markov Theorem (GMT)................................................................... 38
1.9.3 Maximum Likelihood Estimation (MLE) of
Gauss–Markov Theorem (GMT)��43
1.9.4 Gauss–Markov Weighted Least Squares Analysis....................................44
1.10 Susceptible–Infective–Recovered (SIR) Epidemiological Model of COVID........ 47
1.10.2 SIR Model Discussion.................................................................................... 50
1.11 EP Model with Varying Population.......................................................................... 52
1.11.1 Reproduction Number Approach to Binomial Distribution (R0)............. 53
1.12 Machine Learning Model for SARS-Cov-19............................................................. 57
1.12.1 Machine Learning Model.............................................................................. 59
1.13 Models of Machine Learning..................................................................................... 59
1.13.1 Measurement Error ( u )................................................................................... 60
1.13.2 Stochastic Error ( u )......................................................................................... 60
1.13.3 Hidden Gauss–Markov Theorem (HGMT)................................................. 62
1.14 COVID-19 Mathematical Model Approach to Selective Sample...........................65
1.15 Recommendations....................................................................................................... 72
vii
viii Contents
1.16 Study Limitations......................................................................................................... 74

1.17 Conflict of Interest........................................................................................................ 74
References................................................................................................................................ 74
2. Time Series Stochastic Projection Models for the Estimation of COVID Trend..... 79
2.1 Introduction.................................................................................................................. 79
2.2 Time Series Stochastic Models...................................................................................80
2.2.1 Exponential Smoothing by Bootstrap Techniques.....................................80
2.2.2 Holt–Winters (HW) Triple Exponential Smoothing Method...................80
2.3 ARIMA Forecasting Model Approach to COVID Progression Estimation......... 81
2.4 Model Discussion......................................................................................................... 92
2.5 Conclusions................................................................................................................... 92
2.6 Random Walk Markov Chain Stochastic Transient (RMCST) Model.................. 92
2.7 Optimization of COVID Cases from Transition Matrix......................................... 95
2.8 Model Diagnostic Test................................................................................................. 96
2.9 Discussion..................................................................................................................... 96
2.10 Conclusions................................................................................................................... 97
References................................................................................................................................ 98
3. Study of Anxiety and Fear of COVID-19........................................................................ 101

3.1 Introduction................................................................................................................ 101
3.2 Methods....................................................................................................................... 102
3.3 Results.......................................................................................................................... 103
3.4 Discussion................................................................................................................... 111
3.5 Conclusions................................................................................................................. 113
References.............................................................................................................................. 114
4. COVID-19 Gene Sequencing Modeling......................................................................... 117

4.1 Introduction................................................................................................................ 117
4.2 Maxam and Gilbert Method..................................................................................... 118
4.3 Sanger Sequencing..................................................................................................... 118
4.3.1 Chain Termination PCR............................................................................... 119
4.3.2 Separation Based on Size Using Gel Electrophoresis.............................. 120
4.3.3 Analysis of Gel and Identification of DNA Sequence............................. 120
4.4 Long-Read Sequencing Methods............................................................................. 121
4.4.1 Single-Molecule Real-Time (SMRT) Sequencing...................................... 122
4.4.2 Nanopore DNA Sequencing........................................................................ 122
4.4.3 Merits of Nanopore DNA Sequencing....................................................... 122
4.4.4 Massive Parallel Signature Sequencing (MPSS)....................................... 123
4.4.5 Statistical Methods for Testing MPSS Data............................................... 125
4.5 Cauchy Distribution.................................................................................................. 126
4.6 Exponential Distribution.......................................................................................... 127
4.7 Gamma Distribution................................................................................................. 128
4.8 Log-Normal Distribution.......................................................................................... 129
4.9 Logistic Distribution.................................................................................................. 131
4.10
Poisson Distribution.................................................................................................. 132
4.11
Weibull Distribution Model..................................................................................... 133
4.12
Next-Generation Sequencing................................................................................... 134
4.13
Illumina Solexa Sequencing..................................................................................... 134
4.13.1
Procedure for Illumina Sequencing........................................................... 136
Contents ix
4.14 Model Formulation.................................................................................................... 140

4.15 Pyrosequencing.......................................................................................................... 144
4.16 Gene Sequencing Alignment................................................................................... 145
4.17 Alignment Parameters.............................................................................................. 146
4.18 COVID Sequencing.................................................................................................... 146
4.19 Gene Alignment and Its Applications.................................................................... 148
4.19.1 Global Alignment......................................................................................... 148
4.19.2 Scoring Matrices............................................................................................ 149
4.20 Whole Genomic Analysis (WGA)............................................................................ 149
4.21 Discussion................................................................................................................... 155
4.22 Conclusions................................................................................................................. 158
References.............................................................................................................................. 158
5. Real-Time PCR (RT-PCR) for COVID-19 Diagnosis and Changes in

Threshold Cycle (Ct) in Association with Different Parameters............................... 163
5.1 Introduction................................................................................................................ 163
5.2 A High Threshold Value of Ct in COVID-19.......................................................... 165
5.4 Model Output............................................................................................................. 168
5.5 Discussion................................................................................................................... 171
5.6 Conclusions................................................................................................................. 172
References.............................................................................................................................. 173
6. COVID-19 Vaccination Modeling Approach to Public Health Policy...................... 175

6.1 Introduction................................................................................................................ 175
6.2 What Else Does a Vaccine Contain?........................................................................ 177
6.3 Model Formulation—Need for Model Formulation............................................. 178
6.4 Methods....................................................................................................................... 179
6.5 Determination of Vaccination Effects by Statistical Tools or Methods.............. 184
6.6 Herd Immunity.......................................................................................................... 184
6.7 COVID Vaccination Predictive Statistical Models................................................. 194
6.8 Model Construction................................................................................................... 195
6.9 Projection Modeling of COVID Vaccination.......................................................... 205
6.10 Model Output............................................................................................................. 206
6.11 Real Probability of Bayes for Estimation of Vaccination Effect .......................... 209
6.12 Bayes Stochastic Vaccination Model........................................................................ 210
6.13 Discussion................................................................................................................... 212
6.14 Conclusions................................................................................................................. 215
6.15 Recommendations..................................................................................................... 215
References.............................................................................................................................. 215
7. Trend of COVID-19 Surge Projection............................................................................. 217

7.1 Introduction................................................................................................................ 217
7.3 Bayes Weighted Regression Model.......................................................................... 221
7.4 Model Results............................................................................................................. 226
7.4.1 Projective Model of the Third Wave by Using IA Score........................... 231
7.4.2 Calculation Summary.................................................................................. 231
7.5 Discussion................................................................................................................... 232
7.6 Conclusions.................................................................................................................234
References.............................................................................................................................. 235
x Contents
8. Risk Analysis of COVID-19—Vetted by Real Data Sets............................................. 237

8.1 Introduction................................................................................................................ 237
8.3 Numerical Model Output......................................................................................... 241
8.4 Discussion................................................................................................................... 248
8.5 Conclusions................................................................................................................. 250
References.............................................................................................................................. 250
9. Data-Driven Decision Support Model for COVID-19................................................. 253

9.1 Introduction................................................................................................................ 253
9.1.1 Communication-Driven Model...................................................................254
9.1.2 SARS-Cov-19 Data-Driven Model...............................................................254
9.1.3 Document-Driven Model............................................................................. 255
9.1.4 Knowledge-Driven Model........................................................................... 255
9.1.5 Model-Driven Decision Support System................................................... 255
9.2.1 Rayleigh Distribution................................................................................... 257
9.2.2 Levy Distribution.......................................................................................... 257
9.2.3 Pareto Distribution....................................................................................... 257
9.2.4 Laplace Distribution..................................................................................... 257
9.2.5 Gamma Distribution.................................................................................... 257
9.2.6 Logarithmic Distribution............................................................................. 257
9.2.7 Burnt Finger Poisson Distribution............................................................. 258
9.2.8 Skellam (λ1, λ2) Distribution......................................................................... 258
9.2.9 Reciprocal Distribution................................................................................ 258
9.2.10 Maxwell–Boltzmann (MB) Distribution.................................................... 259
9.2.11 Inverse Gaussian Distribution.................................................................... 259
9.2.11.1 Model Results................................................................................ 260
9.3 Bayesian Decision Support Data-Driven Model (BDSDM).................................. 267
9.4 Discussion................................................................................................................... 269
9.5 Conclusions................................................................................................................. 271
References.............................................................................................................................. 271
10. Age-Specific SARS-Cov-19 Incidence Modeling.......................................................... 275

10.1 Introduction................................................................................................................ 275
10.3 Model Output............................................................................................................. 277
10.4 Time Series Stochastic Model in the Prediction of the Second Wave of
COVID in India�� 278
10.5 Model Formulation—Age-Specific Time Series..................................................... 278
10.5.1 Model Output................................................................................................ 280
10.6 Model 1........................................................................................................................ 291
10.7 Discussion................................................................................................................... 291
10.8 Conclusions................................................................................................................. 294
References.............................................................................................................................. 295
11. National Health Policies and Their Perspectives on the Approach to Control
COVID-19 and Other Infectious Diseases..................................................................... 299
11.1
Introduction................................................................................................................ 299
Contents xi
11.2 What Is Health Policy?..............................................................................................300

11.3 Methodological Considerations...............................................................................300
11.3.1 Control of Infectious Disease COVID-19 Pandemic................................ 302
11.3.2 Control of Tuberculosis by NHP................................................................ 302
11.3.3 Control of HIV/AIDS.................................................................................... 303
11.3.4 Leprosy Elimination..................................................................................... 303
11.3.5 Vector-Borne Disease Control.....................................................................304
11.4 Rationality of Health Policy During Emergency...................................................304
11.5 Methods of Formulation of Policy Based on Different Social and
Economic Attributes��308
11.6 Practical Approach to Implementation of Health Policy......................................309
11.6.1 A Collaborative Endeavour......................................................................... 310
11.6.2 A Broad Research Spectrum....................................................................... 310
11.7 Aligning Research with Need and Ensuring Quality.......................................... 311
11.8 Government and Public Responsibilities to Safeguard Policy During an
Emergency Situation�� 312
11.9 How to Formulate Health Policy Research............................................................ 313
11.9.1 Objectives of the National Health Research Policy................................. 314
11.10
Preparedness of Implementation Policy................................................................. 314
11.10.1 What Is Health Policy Implementation?.................................................... 314
11.10.2 What Is the Importance of Policy Implementation?................................ 315
11.11
How to Implement Effective Policies and Procedures......................................... 315
11.11.1 Consultation.................................................................................................. 315
11.11.2 Tailor the Policy to Your Business.............................................................. 315
11.11.3 Define Obligations Clearly be Specific...................................................... 315
11.11.4 Make the Policy Realistic............................................................................. 315
11.11.5 Publicize the Policies and Procedures....................................................... 316
11.11.6 Train All Employees in Policies and Procedures..................................... 316
11.11.7 Be Consistent in Your Policy Implementation.......................................... 316
11.11.8 Review All Policies and Procedures Regularly........................................ 316
11.11.9 Enforce the Workplace Policies and Procedures...................................... 317
11.12
The Challenges of Implementing Health Policy.................................................... 317
11.12.1 What Happens During Policy Implementation?...................................... 318
11.12.2 Who is Involved in Policy Implementation?............................................. 318
11.13
Pilot Study for Implementation Policy.................................................................... 318
11.13.1 What Is a Pilot Implementation?................................................................ 318
11.13.2 How Do You Implement a Pilot Program?................................................ 319
11.14
What Are Pilot Studies Used For?........................................................................... 319
11.14.1 What Are You Trying to Achieve?.............................................................. 319
11.15
Formulation of Uniform Civil Code to Frame Health Policy During the
Pandemic Crisis�� 320
11.16
Propagation of Public Feedback for Policy Implementation................................ 321
11.17
Barriers for Implementing Public Health and Social Measures to
Prevent COVID-19�� 322
11.17.1 Lack of Safety Commitment from Public (Br-1)....................................... 322
11.17.2 Poor Safety Culture (Br-2)............................................................................ 322
11.17.3 Lack of Administrative Commitment and Support at
Community Level (Br-3)�� 322
11.17.4 Lack of Strict Enforcement of WHO Regulations (Br-4)......................... 323
xii Contents
11.17.5 Lack of Resources for Implementing Public Health and Social

Measures (Br-5)��323
11.17.6 Lack of Medical Facilities at Community Level (Br-6)......................... 323
11.17.7 Lack of Door-to-Door Services During Quarantine Period (Br-7)....... 323
11.17.8 Lack of Proper Communication between Health Advisors and
the Public (Br-8)��324
11.17.9 Lack of Government Policies (Br-9)......................................................... 324
11.17.10 Public Stigmatization (Br-10).................................................................... 324
11.18
Responsibilities of Health Professionals, Bureaucrats, and Elected
Members of Parliament to Control the Pandemic under Constitutional
Framework�� 324
11.18.1 The Legal Framework for Combating a Pandemic in India................ 326
11.19
Indian Health Policy—Conclusions........................................................................ 328
11.20
International Health Policy....................................................................................... 328
11.21
Redefining the “High-risk” Group.......................................................................... 329
11.22
A Challenging Time to Deliver, but the Worst Moment to Stop......................... 329
11.23
WHO Policy during the Pandemic Crisis............................................................... 330
11.24
Take-Home Message.................................................................................................. 331
11.25
Conclusions................................................................................................................. 332
11.26
Recommendations..................................................................................................... 332
References.............................................................................................................................. 333
12. Statistical Ethics for Computational Biology and Medical Science.......................... 335
12.1 Introduction................................................................................................................ 335
12.1.1 Importance of Research Ethics................................................................... 337
12.1.2 How to Recognize Predatory Journals...................................................... 338
12.2 Statistical Ethics.......................................................................................................... 339
12.2.1 Honesty..........................................................................................................340
12.2.2 Objectivity......................................................................................................340
12.2.3 Integrity..........................................................................................................340
12.2.4 Carefulness....................................................................................................340
12.2.5 Openness........................................................................................................340
12.3 Research Ethics in Human Interventions...............................................................340
12.4 Educate the Participants about Risks and Benefits...............................................340
12.4.1 Confidentiality..............................................................................................340
12.4.2 Responsible Publication............................................................................... 341
12.4.3 Non-Discrimination..................................................................................... 341
12.4.4 Human Subject Protection........................................................................... 341
12.4.5 Legality........................................................................................................... 341
12.5 Statistical Implications for Research Study............................................................ 341
12.6 Selection of Appropriate Statistical Methods for Testing
Research Hypotheses and Research Implications��342
12.7 Generalized Linear Model (GLM)...........................................................................342
12.7.1 Model..............................................................................................................342
12.7.2 Objective.........................................................................................................345
12.7.3 Model Structure............................................................................................345
12.7.4 Model Assumptions.....................................................................................345
12.7.5 Parameter Estimates and Interpretation...................................................345
12.7.6 Model Fit........................................................................................................345
Contents xiii
12.8 Model Selection..........................................................................................................345

12.8.1 Random State Components.........................................................................346
12.8.2 Systematic Components...............................................................................346
12.8.3 Link Function η or g ( µ )................................................................................346
12.8.4 Assumptions of the Model..........................................................................346
12.9 Model Diagnosis Test................................................................................................ 347
12.10 Model Diagnosis by Information Criteria.............................................................. 347
12.11 Bayesian Analysis...................................................................................................... 347
12.11.1 Random Error................................................................................................348
12.11.2 Systematic Error............................................................................................ 350
12.11.3 Research Hypothesis Is Reliable, but Not Valid....................................... 350
12.11.4 New Research Findings Are Unrealistic Phenomena............................. 350
12.12 Discussion................................................................................................................... 351
12.13 Conclusions................................................................................................................. 352
References.............................................................................................................................. 352
Index.............................................................................................................................................. 355
Preface
Mathematics and statistics are the fundamental sciences to provide conclusive results
for healthcare researchers and policymakers. Contrary to popular beliefs from scientists,
mathematical tools help us extrapolate reasonable results to fight against the COVID-19
pandemic. In the wake of recent global threat from the deadly disease, many countries
have issued immediate countermeasures to control the spread of this disease. In this vein,
analytical interventions are very important to guide policymakers. Mathematicians and
statisticians will thrive on hard work to discover new modeling techniques for the esti-
mation of the exact cause of diseases, development of new algorithms for COVID vaccine
trials, disease management protocol, mass vaccination, diagnostic testing, and treatment
patterns in association with clinical attributes, preventive measures, and policy interven-
tions at global platform. This demonstrated model will provide insights into the mecha-
nisms of transmission, case fatality rate, and the impact on economy and psychological
well-being of humans. Experts gained insights and knowledge from new mathematical
models that led to taking timely decisions in affected areas. The model can facilitate differ-
ent analytical simulation techniques for the estimation of the number of people who might
get infected in pandemic areas and the number of bridge population, tracing of super-
spreaders, and the accurate estimation of incubation and treatment aspects. For example,
from our experience in real data sets of COVID-19 mortality, many previous models from
scientific journals calculated case fatality rate (CFR) based on the ratio of the actual number
of infected persons dead to the total number of persons infected. This kind of estimation
is imperfect because >90% of the population have more than two or three comorbidities.
They are taking treatment for more than a decade. The mean age of the population who
suffered from COVID-induced death is 68–70 years; >68 years is considered as an outlier.
We have to assign scores to individual age groups and formulate a stochastic process for
the estimation of exact CFR. As such being the case, we developed new stochastic con-
vergence models and filled this research gap at global level. Based on all the Draconian
measures, we correlated a real approach with complex analysis. Further, using stochas-
tic ensemble estimation methods, we predicted the actual number of cases infected at
affected sites, and the number of asymptotic cases and the treated and untreated cases
were carefully estimated from stochastic convergence and time series models. On the con-
ceptual framework of COVID-19 pandemic, all answers and solutions lie in mathematics
and statistical tools. These tools can be applied as pragmatic interventions to describe the
exact dynamism of infectious disease propagation among people. As long as mathematical
modeling can simulate population dynamics (disease-free endemic and epidemic equilib-
ria) of the pandemic disease, it can be visually represented using numerical figures and
eye-catching graphs and diagrams. This book consists of 12 chapters. In each chapter, we
demonstrate a new model approach to COVID-19 real-time data sets and also assess how
the disease affects people in the long run, economic catastrophe, and phobia of COVID-
19 in correlation with different quality of life (QOL) domains. The COVID-19 forecasted
models webbing are in all embedded chapters. Chapter 1 describes a mathematical mod-
eling approach to COVID-19 using vetted real data. Chapter 2 demonstrates time series
stochastic projection models for the estimation of COVID-19 trend. Chapter 3 studies the
anxiety and fear of COVID. Chapter 4 deals with COVID-19 gene sequencing modeling.
Chapter 5 explores the changes in the cycle threshold (Ct) level associated with different
xv
xvi Preface
parameters when diagnosing COVID-19 using RT-PCR. Chapter 6 describes a COVID-19

vaccination modeling approach in relation to public health policy. Chapter 7 deals with
the trend of surge of different waves of COVID-19. Chapter 8 performs a risk analysis of
COVID-19 vetted by real data sets. Chapter 9 describes a data-driven decision support
model of COVID-19. Chapter 10 deals with age-specific SARS-Cov-19 incidence modeling.
Chapter 11 describes the salient features of National Health Policies and their perspec-
tives on the approach to the control of COVID-19 and other infectious diseases. Chapter
12 describes statistical ethics for computational biology and medical science. This entire
book covers various advanced mathematical simulation techniques driven by real data
sets (extracted from WHO, CDC open platform, and primary data sets). These analytical
methods will be very useful and help policymakers (WHO scientists) in the implementa-
tion of health prevention policy worldwide, and they also will help research beginners,
postdoctoral degree scholars, and academicians for extending the analytical research on
preventive measures for various infectious diseases.
DM Basavarajaiah,
KVAFSU (B), Bengaluru, Karnataka, India,
B Narasimha Murthy,
B ICMR, Chennai, Tamil Nadu.
Acknowledgments
During the pandemic crisis and unprecedent lockdown, we have taken too many efforts
for acquisition of data, permission for data collection from the competent health author-
ities and also consent obtaining from the patients is greatest challenges at the time of
Pandemic. However, it would not have been possible without the kind support and help
of many individuals, and we would like to extend our sincere thanks to all of them. WHO
and CDC strongly encourage their users to access research data sets for analytical study
purposes worldwide. In this research book, we acknowledge that the greatest credit goes
to the Worldometer Association, CDC, Chinese Center for Disease Control and Prevention,
Chinese Health Authority, and World Health Organization for sharing data in the open
Web platform. We are highly indebted to our competent authority KVAFSU (B) and ICMR,
Government of India, for their moral support and encouragement. Our sincere thanks and
appreciation also extend to the people who have directly or indirectly helped us with the
completion of this entire research monograph.
DM Basavarajaiah,
KVAFSU (B), Bengaluru, Karnataka, India,
B Narasimha Murthy,
ICMR, Chennai, Tamil Nadu.
xvii
Authors
Dr. DM Basavarajaiah is Associate Professor and Head,

Department of Statistics and Computer Science, Karnataka
Veterinary Animal and Fisheries Sciences University (B),
Hebbal, Bangalore. He obtained his PhD from the National
Institute of Epidemiology (NIE), ICMR, Chennai (affiliated
with the University of Madras). His research focuses on
statistical theory, statistical modeling on high-dimensional
data sets in agriculture, medicine, and veterinary and ani-
mal sciences. He has written hundreds of research articles
and published seven academic books in national journals
and Springer Nature group (HIV Transmission Statistical
Modelling, Springer Nature, 2019, and Design Experiments and
Advanced Statistical Techniques in Clinical Research, Springer
Nature, 2020). He serves as an Editorial Board Member and
Scientific Board Advisor for various international indexed journals. He is an Academic
Editor of PLOS One, TJPRC, Science Publication, etc. He is a Life Member of numerous
academic organizations and has received several accolades for his academic and research
excellence “Chartered Scientist” award stalwart by Science Council, the UK, in collabora-
tion with Royal Statistical Society. He is a recipient of the VDGOOD International Scientist
Award and the Best Reviewer Award-2016 from “TRANSSTELLAR” Journal Publications
and Research Consultancy, TJPRC Ltd. (NAAS rated journals). He is a Fellow of Royal
Statistical Society, the UK (London), and a Fellow of Mathematical Society, the UK (London).
He was given Bharathshikshratana and Indo-Dubai Achiever’s Pacific Scientist Award hon-
ored by Global Society for Health and Education Growth, New Delhi, Best Reviewer-2015,
Best Scientific Board Advisor-2016, and Best Editorial and Researcher Award bestowed by
International Academy of Science, Engineering and Technology, the USA. He is an active
member of the Board of Studies and Academic Council of various universities.
Prof. B Narasimha Murthy is a well-known academician

and researcher and a Former Scientist G (Director grade
cadre), National Institute of Epidemiology of ICMR, Chennai.
Presently, he is a National Level Monitor, National Health
Mission, MoHFW, Government of India. He obtained his
PhD from the International Institute of Population Science
(IIPS), affiliated with Bombay University (1985). His area of
research covers mathematical statistics, operational research,
clinical research, public health, demography and vital statistics, mathematical modeling
with respect to medical science, and public health. He has penned more than 100 research
articles and published in reputed national and international journals. He has published
two books in Springer Nature. He serves as an Editorial Board Member and Scientific
Board Advisor of various international indexed MCI- and UGC-recognized journals. He is
an Academic Editor of PLOS One, Science Publication, etc. He is a Life Member of various
academic organizations. He has been honored with several accolades for his academic and
research excellence, viz. Prof. R. N. Srivastava Gold Medal Award, “Bharat Jyoti Award,”
xix
xx Authors
and “Best Citizens of India.” He served as a member of the Board of Studies of various
national universities (University of Madras, Acharya Nagarjuna University, and the
University of Kerala). He is a Visiting Emeritus Professor of Johns Hopkins Bloomberg
School of Public Health, Baltimore, Maryland, and North Carolina University, the USA.
He is a reviewer for national and international journals.
1
Mathematical Modeling Approach to
COVID-19: Vetted Real Data
1.1 Introduction
The novel coronavirus (nCov2019) is also known as COVID-19 or SARS-CoV-2. Primarily,
the disease spreads from one individual to another through droplets released while
coughing and sneezing, hugging or handshaking. These actions would enable the virus
to land on the mouth or nose of nearby people. WHO declared nCov as a pandemic on
March 11, 2020. This global pandemic gregariously affected approximately 7.30 million
individuals, among which 0.16 million have lost their lives and 2.03 million are still suf-
fering from debilitating nCov2019 (WHO, Dec 2020). People of all age groups are infected
by this new virus; older people and people with comorbidities (such as asthma, diabe-
tes, CVD, hypertension, and so on) appear to be more vulnerable, becoming severely ill.
WHO advise people of all age groups to take steps to protect themselves from the virus,
for example by practicing good hand hygiene and good respiratory hygiene. As far as
the COVID outbreak is concerned, the virus seeded outside China and subsequently
got localized, which may be inevitable, unless some kind of draconian measures were
taken at the global level, viz. cancellation of mass gathering, school closures, and institut-
ing work from home arrangements. Since the containment failed in the epidemic area,
local transmission was established for the purpose of migrating to a secured place. A
lot of measures were taken during the previous major outbreaks, e.g., SARS, MERS, or
pandemic influenza, which could serve as useful cited information for the implementa-
tion of causative measures on health policy at a global level. While the lockdown did
mitigate the impact of coronavirus outbreak on the population, it has dire implications
on economic activity, affecting almost every sector. Both private entrepreneurs and gov-
ernments should consider the fine nuances of this impact and respond appropriately to
ameliorate the crisis.
Decision making while managing the health crisis is certainly the most important
task of healthcare workers and is often a very difficult one. This study offers a decision-
making procedure for solving complex problems step by step. It presents the decision
analysis process for both public and public health policymakers, thus enabling them to
formulate the criteria of planner of health policy using different types of information
pertaining to COVID-19 pandemic. We resourced information of varying quality with
due thumb rules and tradition. Mere prediction of disease pandemics is no longer suffi-
cient for addressing such common decisions vis-à-vis prevention and eradication. In gen-
eral, the forces of various mathematical predictions provide accurate decision making
DOI: 10.1201/9781003204794-1 1
2 COVID Transmission Modeling
at all levels of control measures. The decision analysts provide quantitative supports
for the decision makers in all areas of health science, including analysis of economic
impact after disease outbreak. During the intervention of COVID-19, the following table
is essential for a review of the entire spectrum of disease outbreaks at the population
level (Figure 1.1 and Table 1.1).
FIGURE 1.1
(a) Clinical features or Common symptoms of COVID-19. (b) Lung damage by the COVID-19 virus – Cross
sectional view.
Mathematical Modeling of COVID-19 3
TABLE 1.1
Milestones of Infectious Disease Pandemics
Millennia Pandemic
2020 COVID-19
1920 Spanish flu**
1820 Cholera
1720 Indian vole fever
1620 Typhoid
1520 Ron’s syndrome
1420 Black Plague
1320 Taffy leg
1220 Scraphids
1120 Striped taper virus
920 Poppy spots
820 Dericho wheeze
720 Tussle gutter
620 Fatigue
520 Lemon sores
420 Prionic gumdrop gabbies
320 Thoracic deteriorative mites
220 Sternal potex
120 Longerd’s eyeswell
20 Liverbrine amoeba
R0 values do not take into account case fatality rate; **this estimate is
preliminary and likely to change in the course of the outbreak
1.1.1 Main Objectives of This Book

In the present scenario, analytical science is a very important tool in exploring diversified
results of infectious diseases. However, COVID-19 is a deadly disease that can change
the entire spectrum of human life and continuously spread across the world. Even devel-
oped countries are unable to cope up with the geometric progression of the pandemic. The
residual impact of the disease will continue to penetrate and adversely affect the vulner-
able population of both humans and animals for another decade. In this vein, estimating
the impact of the spread of COVID is very important on a global platform to know the
future trajectory and repercussion. This book will explore and formulate new mathemati-
cal modeling that is very relevant to the current situation, and based on these research
findings, policymakers will be able to formulate many pragmatic guidelines and also
frame steps to support the current crisis. Here we explore many advanced mathematical,
statistical and epidemiological modeling approaches and attempt to explore other activi-
ties perceiving mathematical and statistical discipline for solving the real-world problems.
The following salient objectives were considered to formulate this entire book. An entire
intervention of COVID is fully described by new mathematical and statistical modeling of
the disease spread worldwide. We developed new mathematical and susceptible-infectious-
susceptible (SIS) stochastic process models for the estimation of reproduction number R0
and to determine the epidemic threshold level. The immediate objective of this book is to
explore the parameterization of real data and to devise models to intervene at appropriate
levels that would bring down the COVID outbreaks to a manageable level. Human beings
are endowed with millions of neurons, and each segment may activate positive and nega-
tive feelings. The socioeconomic impact of the pandemic pushes the individuals to severe
mental illness (SMI); furthermore, always there is a possibility of contracting COVID-19
infection and critically affecting the outcome of other health issues, leading to poor prog-
nosis. In this context, we explore the impact of COVID on human health domains at the
population level and also test the hypothesis using advanced modeling techniques. This
estimation of COVID-19 projection in different time periods is more benefited to estimate
the different health measures associated with COVID, including quarantine of suspected
cases, and lockdowns may negatively affect the mental health status of people suffer-
ing from one or more comorbid conditions. The present research findings will support
psychology to manipulate the change of environment, disruption of services, and reduce
stress and isolation. COVID is not only a global pandemic and public health crisis; as per
The Economic Times and other research groups, it has severely affected the global econ-
omy and financial markets. The literature reveals that there will be a significant reduc-
tion in income, rise in unemployment, and disruption in the transportation services and
manufacturing industries. These are some of the consequences of the disease mitigation
measures that have been implemented in many developed and developing countries. It
has become clear that most national economic policy organizations underestimated the
risk-based economic attributes from a frequentist (without credibility and real probabil-
ity) approach, and many results showed the biased estimation of the economic effect of
rapid COVID-19 spread and were mostly reactivate in their pandemic crisis. In this para-
digm, we have developed advanced time series structural stochastic models for the esti-
mation of accurate surges in the projection of COVID intervention at a global platform
using real-time data. SARS-Cov-19 infection is a complex interaction between the microbe,
the environment, and the human host. Genetic variation among humans has only rarely
been linked to complete resistance to infection by a specific genetic trait. In this crust of
the problem, this study has the ability to derive the impact of genetic traits leading to com-
plications in the management of COVID-19, drug resistance, and translating these genetic
findings to improved patient care. By and large, COVID-19 has been managed by lifesaving
drugs and ancillary systems. Many countries have been using hydroxychloroquine (HCQ)
for treating COVID; also, it is presumed that HCQ can reduce the case fatality rate (death
rate). However, many research studies across the world showed hydroxychloroquine to
inhibit the entry of severe acute respiratory syndrome coronavirus2 (SARS-Cov-2) into epi-
thelial cells in vitro, but some clinical studies found no evidence of reduction in mortality
when treating patients with COVID. In this vein, we attempt to conduct a meta-/systematic
analysis of HCQ to evaluate its effectiveness for the prevention of COVID mortality and
also we will demonstrate pharmacokinetic models associated with COVID p andemic in
the second edition.
COVID surveillance is a primary factor to prevent the spread of the disease; based on
surveillance approach, we need to forecast the disease surveillance modeling for taking
disease control measures (detect new cases and clusters in the community). Wherever it’s
feasible, testing should be done as a primary intervention. Many research groups opined
that testing facilities, such as drive-through sites or fixed sites in community buildings, are
needed to be established to capture COVID cases at population level. Fast reporting of data
and complex data analysis are great challenges to identifying new cases and clusters in
affected areas. Therefore, only a minimum number of data variables are considered from
the infected person or affected areas. In this pragmatic scientific approach, policymakers
have their work cut out to estimate various projection points using limited data sets. To
meet the international standards, we need to focus on new mathematical algorithms for
the window period as well as advanced infections. In view of these research gaps, the
present research study discusses various issues of surveillance and formulates new sur-
veillance models (how to select the sample, mass testing for diagnostic accuracy, and treat-
ment regimens). We also forecast the small area estimation for projecting expected cases of
COVID at national and global levels.
The nCov19 pandemic has plunged the world into a medical and economic crisis; many
analytical research papers have been published worldwide for the benefits of society from
the aspect of identifying the control measures (Figure 1.2). It has created a tidal wave; the
entire globe struggles to grab hold of the scope and scale of the pandemic. The technical
operation is a very essential tool for managing the pandemic crisis situation; it stepped up
filling the gap with a research dashboard and is eagerly awaiting normalcy, modeling
efforts to predict epidemic burden and hospital needs. In the face of uncertainty, these
simulations or predictions will provide comfort and tangible facts. In addition to the pre-
ventive measures, mathematical and statistical intervention is very important for us to
extrapolate the epidemiological and preventive aspects from the newer analytical
approach despite making a significant progress in the past few decades regarding public
health concern; yet, there are many scientific issues that remain to cope with, and substan-
tial challenges have been posed to significantly improve public health emergency in China
and globally (IDM editorial statement, 2020). As per the realistic fact of over 300 million
people crossing the mainland of China’s border each year, the experts of the WHO’s emer-
gency committee have not yet reached a consensus of whether the spreading of the new
coronavirus (COVID) is a public health emergency of international concern requiring a
coordinated and integrated response. As recognized by the same WHO, mathematical
models, especially those timely, play a key role in informing evidence-based decisions by
health policies drawn by the policymakers. Many mathematicians demonstrated newer
models for curbing this infectious disease and its epidemic mechanism worldwide (Patel
and Spouge, 2020), estimating the basic reproduction number of the pathogen in a single
host. The models describe the expected number of host cells infected by a single infected
End of
I out
Out Last
Intervention record break
Case break declared
case
Case detection
Risk assessment Capacity building
Intervention plan
Lesson learned
Intervention
Surveillance Policy information and research
Implementation
FIGURE 1.2
Flowchart of risk analysis from statistical simulation.
cell. The phylogenetic models can estimate an initial R0 using only sequences sampled
from the pathogenic population during its exponential growth at early stage; the growth
rate was simulated based on the partial differential equation (PDE). The estimates of R0
have several potential applications to investigators interested in the progress of infection
in single host, including (i) timing the pathogen’s movement through different microenvi-
ronments, (ii) timing the change points in the pathogen’s mode of spread, (iii) quantifying
the impact of different niches on pathogens, (iv) quantifying subtle changes in infectivity
in therapeutic trails, and (v) providing a variable predictive of the clinical efficacy of pro-
phylactic therapies. Demongeot et al. (2012) fitted a mathematical model to know the
potential outbreak of infectious diseases; the fitted model helps to explore the contagious
dynamism of virus and the impact of numerous variables ranging from the micro host
pathogen to the host-to-host interactions, as well as the prevailing ecological, social, eco-
nomic, and demographic factors across the globe. The model discusses the main approach
to reproduction number R0 and also serves as a formidable tool for policymakers at the
global level (Coburn et al., 2009; Siettos and Russo, 2013).Gul Zaman et al.’s (2017) mathe-
matical modeling techniques have been a valuable tool for the analysis of dynamics of
various infectious diseases and for the support of control strategies development in recent
years (Coburn et al., 2009). It is an inclusion platform to explore new ideas, thoughts, and
discussions of major challenges and achievements on quantitative behaviors of infectious
diseases and their control. Mathematical modeling is used to formulate and compile com-
partmental infectious diseases and will induct newer applications to specific infectious
diseases and prevention strategies. In recent years, our understanding of infectious dis-
ease conditions and prevention measures has greatly been increased by mathematical and
statistical modeling. The modeling process is important, existing areas to inform policy-
making decisions at the highest levels, and playing a major role in the field of qualitative
and quantitative epidemiological applied research. The transmissible nature of infectious
diseases makes them fundamentally different from noninfectious diseases, so the recent
analytical interventions driven by the classical epidemiology approaches are often valid
and hence lead to correct conclusions about the health economic analysis on theoretical
and practical approaches. Sudhanshukumar et al. (2020) developed and analyzed a deter-
ministic Zika model considering both vector and sexual transmission routes with the
effect of human awareness and vector control in the absence of disease-induced deaths.
The theoretical analysis shows that the disease-free equilibrium is locally and globally
asymptotically stable (R0<1). Hong Zhang et al. (2020) demonstrated a compartmental
model on Wolbachia-infected mosquitoes, the primary vector responsible for transmis-
sion of dengue and Zika virus. The fitted model derived five steady states, two of which
are locally asymptotically stable. One of these stable steady states has no Wolbachia-
infected mosquitoes, while in other steady states, all mosquitoes are infected with
Wolbachia. They applied optimal control theory to find the release method that will drive
the mosquito population close to the steady state with only Wolbachia-infected mosqui-
toes in a 2-year time period. Villela (2020) fitted a discrete-time forecasting epidemic
model. The model aimed at estimating the number of cases ahead of time during an epi-
demic; the dynamic model helps to predict the number of cases in an epidemic, which
depends on determining a few defining factors such as its starting point, the turning
point, and the growth factor and size of the epidemic in the total number of cases. The
fitted model enables us to derive equations that permit both estimating key dynamic
parameters and forecasting figures simultaneously at greatest precision. Gerardo et al.
(2020) proposed a mathematical model to simulate chikungunya spread; the compartmen-

tal model is implemented in a C++ cellular automata code defined on unstructured trian-
gular grids and space visualizations with Python. A similar study was reported by
Coburn et al. (2009). Pneumonia is one of the leading causes of mobility and mortality in
children under 6 years and the elderly, especially in developing countries. The model was
developed to know the anticipation of its spread and formulation of vaccination. The
deterministic model of Otoo et al. (2020) was fitted considering the symptomatic carrier.
The model results clearly envisage that the DFE is stable only if the basic reproduction
number R0<1. If R0>1, the endemic equilibrium is globally stable and the disease persists.
Numerical simulations on the system show that with effective vaccine interventions,
infections can be eradicated in the long term. The growth model is important for the
severity of the epidemic and is also closely correlated to the basic reproduction number
(R0). An estimated growth rate from the epidemic curve can be a challenging issue of mas-
sive data sets of infectious diseases, because it decays with time and the accurate figure
cannot be gained from the curve fitting estimation modeling. Therefore, for fast epidem-
ics, the estimation is subject to overfitting due to the limited amount of data; the curve
fitting epidemiological model is very useful for policymakers for the implementation of
newer policies at a very early stage of infectious disease epidemic (Juling Ma, 2020).
Considering the public health concern at international level and policy-making interven-
tions, the mathematical tool is very important for scientists, researchers, and health policy
makers for taking preventive measures against the novel coronavirus worldwide; in antic-
ipation with overall modalities, this mathematical model will assist stakeholders in the
timely decision-making processes. On the contrary, the present research monograph aims
to build mathematical, epidemiological, and statistical modeling to know the real value of
reproduction number (R0), disease status, endemic and epidemic equilibria at population
level, virus virulence, transmission rate, etc. The present research monograph helps poli-
cymakers, healthcare specialists, and epidemiologists to draw accurate decisions at the
right time for solving real-world problems of epidemics or spreading of new coronavirus
(SARS-Cov-19) on public health emergency international concerns, and it can also support
the implementation of new policy interventions worldwide. Many academic research
institutes have developed SARS-Cov-19 mathematical modeling on their own objective of
interest (Figures 1.3 and 1.4; Table 1.2).
A compartmental mathematical model of COVID-19 pandemic was demonstrated, which
played an important role in the ongoing crisis. It has been used to design various public
health policies that are instrumental in many of the social distancing measures instituted
worldwide The derived mathematical modeling of COVID-19 pandemic using the epidemi-
ological data in Italy estimated an epidemic trend over the period after April 4, 2020. The geo-
metric progression was estimated by the ARIMA model. The main advantage of this model
is that it is easy to manage and demonstrates time series data sets. Moreover, it may give the
first understanding of basic trends, by suggesting the hypothetic epidemic inflection point
and final effective size. The fitted agent-based model predicts the spread of an infectious
disease based on behavioral population. They found that reducing the extent of unethical
advice circulating in social media by just 10% will end up in at least 20% of the population
not sharing the fake news, which resulted in reduced severity of the disease outbreak. All
the reasons affirm the emergency and importance of risk communication. Vaishya et al.
(2020) studied the impact of SARS-Cov-19 pandemic in India, which posed a devastating
effect on humankind across the world. Its spread is the result of it being a highly contagious
FIGURE 1.3
Mortality due to Infectious diseases in the preceding millennium at the intervals.
FIGURE 1.4
Trend of COVID-19 research articles published worldwide for policy intervention.
viral pathogen. Its spread in India is universal, and nearly 3 million people were affected.
As per the research findings, the direct death rate has been around 2% and the recovery
rate being >70%, which are promising indicators. Multiple lockdowns by the Government
of India has helped in gearing up the healthcare sectors and significantly improving the
availability of personal protection gears and medicine, availability of beds, and training of
healthcare workers to deal with this deadly disease developed structural equation models
and neural network techniques with the data collected from young adults in Bangladesh.
TABLE 1.2
Different Mathematical Models Developed by Institutions Worldwide
Reference URL Link
IHME SARS-Cov-19 predictions
Los Alamos National Laboratory COVID-19 confirmed and https://covid.bsvgateway.org. Opens in
forecasted case data new tab
University of Geneva and Swiss Data Science Center, SARS-Cov-19 https://renkulab.shinyapps.io/Covid
epidemic forecasting epidemic forecasting. Opens in new tab
Ferguson et al. (2020). Imperial College COVID Response Team, www.imperial.ac.uk/media/imperial-
Report 9 college/medicine/mrc-gida/2020-03-16-
Covid- Report-9.pdf. Opens in new tab
Kissler et al.(2020). Projecting the transmission dynamics of COVID https://doi.org/10.1126/science.abb5793.
through the post-pandemic period Opens in new tab
Modeling the impact of social distancing, testing, contact tracing, https://cosnet.bifi.es/wp- content/
and household quarantine on second-wave scenarios of the uploads/2020/05/main.pdf. Opens in
COVID-19 epidemic new tab
Hellewell et al. (2020). Feasibility of controlling COVID-19 outbreaks https://doi.org/10.1016/
by isolation of cases and contacts S2214-109X(20)30074-7
The results showed that people who are driven by self-promotion and entertainment, and
those suffering from deficient self-regulation are more likely to share unverified informa-
tion. Exploration and religiosity correlated negatively with the sharing of unverified infor-
mation, since exploration also increased social media fatigue. The findings indicate that the
different purposes of social media introduce problematic consequences, such as increased
misinformation sharing, which formulated an extended mixture model to be used in rich
settings to derive asymmetric daily mortality patterns. Health service needs were fore-
casted using a microsimulation model that estimated hospital admissions, ICU admissions,
length of stay, and ventilator needs using the data available on clinical practices in COVID
patients. The demonstrated model presumed that those jurisdictions that have not imple-
mented school closures, on-essential business closures, and stay at home orders will do so
within 20 days. The outbreak will place a load on health system resources well beyond the
current capacity of hospitals in the USA and EEA, especially ICU care and ventilator use.
These model estimates can help inform the development and implementation of strategies
to mitigate this gap, including reducing non-SARS-Cov-19 demand for services and tempo-
rarily increasing system capacity worldwide. Mathematical models of SARS transmission
are used to estimate the infectiousness of SARS from the rate of increase in cases, to assess
the likelihood of an outbreak when a case is introduced into a susceptible population, and
draw preliminary conclusions about the impact of control measures. The following formula
was used for determination of reproductive rate: R = 1 + λv + f(1 – f) (λv)2, where λ = ln [Y(t)]/t
is the exponential growth rate of the epidemic, calculated as the logarithm of the cumulative
number of cases by time t since the first case divided by the time required to generate these
cases from a single case; v is the serial interval; and f is the ratio of the mean latent period,
i.e., time from infection to onset of infectiousness, to the serial interval. The model was
constructed based on real-time series data sets of SARS, and serial intervals were captured
to calculate the sum of the mean latent period and the mean duration of infectiousness; nei-
ther of these time periods is well defined for SARS. Since there have been no reported cases
of transmission of SARS during the pre-symptomatic period, there is substantial evidence
of transmission immediately after the onset of symptoms, suggesting that the period of
infectiousness begins with the onset of symptoms. As per the structural time series model,
the mean incubation period has been variously measured as 5 days and 6.4 days, suggest-
ing that the study finds reasonable values for f to be in the range of 0.5–0.8. Except for the
longest serial intervals, the estimates of “R0” are relatively insensitive to varying population
size. If a proportion “a” of infectious persons are asymptomatic and differ symptomatic
only in that they have infectiousness “b” rather than b, then the fraction of “N” is ulti-
mately symptomatically infected during the course of an epidemic in an SIR model ( 1 − a ) p,
where p is the fraction of the population that is ultimately infected, given implicitly by
equation p = 1 – exp(–R0p), where “R0” is defined analogously to the definition of “R” in
the main text. This is a direct generalization of the usual formula for the final size of an
epidemic and is linear because we assume that each case, regardless of its source, has equal
probability (1 – a) of being symptomatic. More generally, if these assumptions are met, the
ratio of symptomatic to asymptomatic cases will be (1 – a); a (discounting the latent cases).
1.2 Anatomical Structure of COVID-19 Virus

Small envelopes with full club-shaped glycoprotein projections appear on the cell wall of
the nCov19 (Gwaltney et al., 1985) (Figure 1.5). Hence, the coronaviruses (and toroviruses)
are mainly classified together on the basis of the crown or halo-like appearance on the enve-
lope glycoproteins, and distinct characteristic features of their chemistry and replication
(Myint et al., 1994). Most human coronaviruses fall into one of the two serotypes: OC43 and
Envelope
Spikes
Membrane
ssRNA
Nucleocapsid
FIGURE 1.5
Cross sectional view of nCov2019 (Covid).
Infectious
agent
Susceptible
Reservoirs
host
COVID
Portal of Portal of
entry exit
Means of
transmission
FIGURE 1.6
Disease transmission mechanisms.
229E (Gwaltney et al., 1985). This virus causes acute, mild upper severe respiratory infection
in human beings (at inception stage, common cold, fever, and cough) (Figure 1.6). The spheri-
cal or pleomorphic enveloped small flakes contain single-stranded ribonucleic acid (RNA)
associated with a nucleoprotein within a capsid comprised of matrix protein (Gwaltney
et al., 1985). Schmidt et al. (1986) formulated the model based on mRNA to form a unique
structure that looks like a nested set sharing a common 3’-end. The new bunch of virions
were precluded by budding significantly from host cell membranes (Tyrrell et al., 1993).
Transmission usually takes place due to the airborne droplets from the nasal mucosa of the
infected person. Virus replicates locally in cells of the ciliated epithelium, causing damage
and inflammation. The appearance of antibody in serum and nasal secretions is followed by
resolution of the infection (Sanchez et al., 1990). Biologically, the immunity wanes within a
year or couple of months. The incidence rate shoots up in the winter season, assuming a form
of localized epidemic driven for a few weeks or months (Sanchez et al., 1990; Gwaltney et al.,
1985; Tyrrell et al., 1993). The same serotype will drastically turn to an epidemic area after
several years. The main symptom of nCov is cold, and it cannot be distinguished clinically
from other colds in any individual (Tyrrell et al., 1993). The laboratory diagnosis has been
made on the basis of antibody titers in paired sera. Since the virus is very difficult to isolate
(Tyrrell et al., 1993), nucleic acid hybridization tests are now being introduced at global level.
1.3 Virus Incubation Period

The incubation period is the period from the time of exposure to the virus until the devel-
opment of symptoms of disease; the COVID-19 virus incubation period is estimated to be
between 2 and 14 days (CDC, March 2021b). As per the WHO, the estimated value range
will most likely be narrowed down as more data get accumulated. The comparison of the
incubation periods of various kinds of diseases is presented in Table 1.3. In other words,
incubation means the time between catching the virus and beginning to have symptoms
of the disease. Most estimates of the incubation period for SARS-Cov-19 range from 1 to 14
days (calculated based on upstream data) (Table 1.3).
1.3.1 Disease Carriers
In some infectious diseases, either due to inadequate treatment or immune system response,
the disease agent is not completely eliminated, leading to the carrier state. A carrier is defined
as an infected person or animal that harbors specific infectious agents in the absence of dis-
cernible clinical disease and serves as a potential source of infection for others (asymptomatic
cases of COVID are considered as disease carriers or bridge population) (Figure 1.7). A carrier
may be classified into (i) active carrier—those that have an overt clinical case of the disease;
(ii) convalescent carrier—those that have largely recovered but continue to harbor a large num-
ber of pathogens; (iii) asymptomatic carrier—those that apparently show health but can carry
the pathogen; however, they are not ill or exhibit any symptoms; (iv) incubation carrier—those
that incubate the pathogen in a large number but are not yet ill; and (v) chronic carrier—those
that harbor the pathogen for months, years, or lifetime after recovering from the illness.
An infectious agent is any disease-causing microorganism (pathogen); the source of
infection is the starting point for the occurrence of a communicable disease. The infection
will transmit through infected person or animal, objects or substances from which an
infectious agent passes or it is disseminated to the host (immediate source); a reservoir is
any person, animal, arthropod, plant, soil, or substance or a combination of these in which
an infectious agent normally lives and multiplies and primarily survives on it and where it
reproduces itself in such a manner that it can be transmitted to a susceptible host. It is the
natural habitat of the infectious agent. The reservoir can be classified into human, animal,
and non-living reservoirs.
The clinical illness of COVID may be mild/moderate, typical or atypical, and severe or
fatal. Epidemiologically, mild cases of COVID may be more important sources of infection
than severe cases, because they are ambulant and spread the infection wherever they go,
whereas severe cases are usually confined to bed. The spread of disease in manifold replica-
tions from the infected person is diagrammatically represented in Figure 1.8.
Type of Portal exit

carriers
Urinary
Primary, Intestinal
COVID Index case
cases
and Carriers Respiratory
Secondary
Cases
Others
Clinical cases (mild, Duration

moderate and severe)
Temporary
Subclinical and latent
infection cases
FIGURE 1.7
Mechanism of the spread of disease.
Severely infected Asymptomatic Symptomatic
FIGURE 1.8
Mechanism of the spread of disease.
FIGURE 1.9
Mode of transmission of infectious diseases.
• COVID index case—an infected person who comes to the attention of public
health authorities.
• Primary case—the first case of SARS-Cov-19 introduced into the population unit.
• Secondary case—the person who acquires SARS-Cov-19 infection from an expo-
sure to the primary case. Borne = uniformity to be maintained in Figure 1.9.
The incubation period, the time taken from pathogen exposure to the onset of disease, pro-
vides valuable information about disease transmission mechanisms, besides facilitating
the policy intervention in exposed area, and allows us to take up immediate control mea-
sures, such as contact tracing of the infected person and estimating quarantine timeline
for people who are infected by the pathogen or those who came in contact with an infected
person. Moreover, the incubation period can help health professionals effectively diagnose
a disease based on observed and unobserved symptoms by considering the clinical his-
tory. There are several determining factors for the incubation period, including the route
of pathogen transmission, pathogen load, and functionality of the host immune system.
The most reliable way of estimating the incubation period is to methodically study case
reports that involve patients with single pathogen exposure. However, in case of subjects
who are exposed to the pathogen multiple times, it is impossible to determine which expo-
sure triggered the disease onset (Figure 1.10).
Table 1.3 depicts the incubation periods of various diseases presented in the form of
descriptive statistics, as per the Worldometer Section report published on February 18,
2020. SARS virus incubation period was 2–7 days (IQR 1.5–6.95 days); the incubation
period of MERS was 5 days (IQR 1.22–5.5 days); the mean incubation period of swine flu
was 1–5 days and may be as long as 7 days (IQR 2–7.12 days); and the novel coronavirus
being more virulent has an incubation period of 2–14 days, and the onset of symptoms may
occur at 1–2 days (IQR 3–13.47 days).
FIGURE 1.10
COVID progression in majority of cases.
TABLE 1.3
Overview of Incubation Periods of Various Viral Diseases
Virus Incubation Period
SARS 2–7 days (as long as 10 days)
MERS 5 days (range 2–14 days)
Swine flu 1–5 days to as long as 7 days
Seasonal flu 2 days (range 1–4 days)
**Novel coronavirus (COVID-19) 2–14 days or 0–24 days
** Estimated range value will be most likely narrowed down as more data are made
available; source data: Worldometer Section, reported on February 18, 2020.
1.3.2 Case Fatality Rate (CFR, %)

As per the epidemiological and disease intervention, CFR is an important domain to know
the accurate risk or case fertility ratio; in epidemiology, it is the proportion of people who
die from a specified disease among all individuals diagnosed with the disease over a cer-
tain period of time. The CFR typically is used as an estimate in the severity of diseases and
is often used for predicting disease course or outcomes, where comparatively high rates
are an indicative phenomenon of relatively poor outcomes. It can also be used to evaluate
the effect of new treatments, with measures decreasing as treatments improve. Usually,
CFRs are not a constant term; they can vary between population and geographical loca-
tions with respect to time, depending on the interplay between the causative agent of the
disease, the host factor, the pathogen, environmental factors as well as therapy and patient
management with life support treatment.
TABLE 1.4
An Overview of COVID Case Fatality Rate with Respect to Age Group
Age (years) Death Rate (%) P-Value
80+ 14.80 ≤0.000
70–79 8.00** ≤0.000
60–69 3.60 ≤0.038
50–59 1.30 ≤0.026
40–49 0.40 ≤0.081
10–39 0.20 ≥0.001
<9 0.00 –
Male 2.80 ≤0.000
Female 1.71 ≤0.000
** Estimated range value will be most likely narrowed down as more data become
available; source data: Worldometer Section, reported on February 18, 2020.
No. of deaths from a specified disease at defined period of time

CFR ( % ) = × 100
No. of individuals diagnosed with the disease during that time
Table 1.4 shows the COVID-19 fatality rate with respect to age (years); the case fatality rate
was measured from the real data sets. Majority of the patients who died were in the age
group >80 years. Besides, in patients with preexisting illnesses that put patients at a higher
risk, CVD, diabetes, chronic respiratory illness, and hypertension are the major predictors
of increased fatality in the geriatric population (>80 years), the sex ratio is 3:1, and the aver-
age fatality was 2.80% in males and 1.71% in females.
1.3.3 COVID-19 Transmission Mechanisms

Many scientific studies pertaining to the extrapolation of the transmission mechanisms
clearly identified that it is caused by SARS-COV-2 virus, which spreads between people,
mainly when an infected person is in close contact with another person. The virus can
spread from an infected person’s mouth or small liquid droplets from the nose when they
cough, sneeze, speak, sing, or breathe heavily. An uninfected person touching a contami-
nated surface and then touching his/her eyes and nose frequently can get infected.
The change in mortality percentage of COVID is presented in Figure 1.11. As of January
2022, the percentage change was 76%. Majority of the death cases were found at early incep-
tion of the COVID; over the period, the change in the death percentage was significantly
reduced. By February 18, 2020, the cumulative percentage change in death was 7.0%, due to
the preventive measures and effective quarantine adopted in the affected areas (Figure 1.12).
1.4 Epidemiological Aspects of nCov2019 (SARS-Cov-19)

Coronavirus is a family of virus common in animals, with newest deadly strains (novel
coronavirus) identified in Wuhan, China (WHO, 2019). Middle East respiratory syndrome
(MERS) and severe acute respiratory syndrome (SARS) are viral respiratory illnesses caused
by a coronavirus. In 2002, SARS broke out in Guangdong, where a farmer in Shunde District
Wuhan
Droplets generated Touching a

when an infected contaminated surface
person coughs, Large Multiplication and then touching
sneezes or speaks your eyes, nose
FIGURE 1.11
Mechanism of SARS-Cov-19 transmission at Population level (N).
FIGURE 1.12
Change in total percentage of death from Jan 18 to Feb 2020.
of Foshan City was thought to be the first case of infection. In 2003, China notified five
deaths; on December 8, 2019, a patient in the city of Wuhan sought for medical help for
pneumonia-like symptoms, and on December 31, 2019, Chinese authorities alerted the WHO
of a series of pneumonia-like cases in Wuhan. After a consistent decrease since the end of
January 2022, the number of new weekly cases rose for a second consecutive week, with a
7% increase reported during the week of March 14 to 20, 2022, as compared with the previ-
ous week. The number of new deaths has been on a decreasing trend (-23% compared with
the previous week). As of March 2022, over 468 million cases have been confirmed and
over 6 million deaths have been reported globally (weekly epidemiological report WHO,
March 2022). Mathematically, the disease reproduction number R0 increased from 1.4 to 2.5
(CDC, 2019). The transmission of nCov2019 occurs through the air by coughing and sneez-
ing, close personal contact such as touching or shaking hands, and touching of objects or
surface with the virus on it and then touching your mouth, nose or eyes. As per the WHO
report (2022), the common signs of infection are fever, cough, diarrhea, shortness of breath,
and breathing difficulties; infection-like symptoms were expressed. There was no vaccine or
antiviral drug for curing the disease, but only the symptoms could be ameliorated.
1.5 Economic Impacts of Novel Coronavirus

An economic impact assessment is a very important estimation tool to know the trend of
gross loss in the economy in terms of the GDP of the country (IHS, market, CIPS, 2020). It is
cited that the epidemic of novel coronavirus deleteriously affected the economy of China in
terms of decline in stock market process, shutdown of new production, and closed borders
and regulation on tourism. However, the Chinese demand fell by 1% due to the debilitating
virus of nCov2019; low- and middle-income countries lost $4 billion worth of goods exports;
and $0.60 billion of ecotourism receipts fell. The oil price declined $55.70 billion, approxi-
mately 5% amid lower global demand. According to WHO report and vulnerability index
at the global level, the countries at high risk are Sri Lanka, Vietnam, and the Philippines.
Sub-Saharan Africa could also lose up to $4 billion worth of exports as the outbreak damp-
ens the Chinese and global demands. The sudden outbreak of nCov2019 will have signifi-
cant impacts on the poorest economies, even if they do not have confirmed cases (WHO,
2020). The global growth fell from 3.3% to 3.0%. As per the stock market report of China,
the impact of novel coronavirus outbreak will be mostly felt by countries with close links
to China, for example, through trade, investment, or the movement of people (migration
and immigration). Mongolia, Cambodia, and Laos are the most affected Asian countries
followed by Myanmar, the Philippines, and Vietnam. In global economic sentiments, the
indirect economic impact of nCov2019 on national and global markets and also negative
reflect was seen in falling prices of Oils (20%), Copper (7%), estimated (5%) decline over
1 year (20% in this cohort) would lead to a loss of $3.1 billion in the price of mineral fuel
exports from sub-Saharan Africa. Although the economic impact is negatively correlated in
Southeast Asia, there are losses in Central Asia and Europe. The preventive measures are
very important to be addressed as they could impact the economy through the following: (i)
Individual affected countries need to implement a range of health-related national policies
and information campaigns to inculcate the transmission mechanism of virus. (ii) We must
examine the potential economic fallout and spillover effects our global vulnerability index
clearly encompasses to examine the judicial limits of direct exposure to the above debilitat-
ing virus through trade, investment, shares and stock exchange, movement of population or
people, etc. (Figure 1.13).
Based on the CDC (2022a) report, the illness of Covid will be mild, moderate and severe.
The symptoms at inception of disease are very less, and in the latter part of the infection,
the severity of illness is more over a period of time. CDC has noticed from the day of 2–4.
At day 9, acute respiratory disease syndrome (ARDS) developed; between 10 and 11 days,
the patient becomes critically ill and is shifted to the intensive care unit (Figure 1.14). The
symptoms include fever, cough, and shortness of breath; CDC believes at this time that the
symptoms of COVID may appear in as early as 2 days to as long as 14 days post-exposure.
FIGURE 1.13
Projected cases at the early seed of SARS-Cov-2.
FIGURE 1.14
Timeline of onset of coronavirus (ARDS—acute respiratory disease syndrome).
1.6 Mathematical Model for the Prediction of

Novel Coronavirus (nCov2019)
The mathematical model was fitted on the salient assumptions that the infected and crude
mortality rate per capita (nCov2019) could be varied with different geographical region
and distinct with different rate of infection (epidemic area) at the global level (random pro-
cess techniques were used to extrapolate the model building). The infectivity of various
compartments was portioned based on the fundamental principles of standard operating
protocol (SOP) of medical care/healthcare system (WHO guidelines) to prevent the spread-
ing of the deadly virus. Also, the asymptomatic and symptomatic sub-compartments were
smoothened to know the geometric progression of nCov2019. The recruitment rate into
human population is by birth and is kept constant; the deaths in the human population
are neither natural nor nCov2019 induced and are constants; the proportion of treated sus-
ceptible per unit time are regarded as the subjective inclusion of our research. The recov-
ered individual may become susceptible to infection again during a multiple outbreak or
in the future outbreak; distinct parameters with selected sites were considered for model
building. Arbitrarily we assumed 50% of the identified affected population who have been
treated by the healthcare specialists and also they were vaccinated (susceptible popula-
tion). This information directs us to the estimation of the proportion of susceptibility that
were treated or vaccinated per unit time as α h = 0.50, and also we assume that the loss of
temporary immunity from recovery λ h , and that of vaccination ϕ h to become susceptible
again is very small due to effective treatment and the drug or vaccine. This trivial changes
will help us in the estimation of varied parameters in a variety of model settings λ h = 0.07
and ϕ h = 0.03, respectively. For the model building concern, the affected (exposed) and sus-
ceptible population datasets (CDC, 2021a) were extracted from the CDC database and also
different datasets were reutilized for the model simulation. We used the datasets approxi-
mated using the hypothetical total human population of 1,000,000 distributed across the
selected compartments of the model in the human host parameter.
1.6.1 Variables Used for Model Building

Figure 1.15 shows that the novel coronavirus has been susceptible to human population
and is affected by many various causative agents such as raw meat, seafood and other
forms of food that were consumed by the population, the Sh recharged by infective popu-
lation (I) and same intervention was moved to treated population Vh or gets into contact
with an infected vector (touching, hugging, sneezing, infected droplets spread through
air, usage of toilets, sharing of common articles, kissing, frequent rubbing of nose and eyes
without hygiene, common transportation, migration from one place to another, exposure
to mass or public places, sharing of injecting drug needles, etc.) I v and becoming exposed
(if not maintained proper hygiene) to move to Eh. Thereafter, the incubation period of virus
will take place over time “t”, and then individuals get infected and move to I h , a or I h , s . They
recover and are moved to Rh or die naturally or due to nCov2019. Further, a proportion
of the treated human Vh may lose temporary immunity conferred by the vaccine after
some time due to the depletion of the efficacy of the administered drug and treatment
Transmission
Suscepble Infecon Treated (T)
Recovered Death (D)

Again, susceptible due to
Some accidental cause
Relapsed
FIGURE 1.15
Basic architectural plan for model building.
and becomes susceptible again, thus moving back to Sh. The vector Sh will be deleteriously
pooled susceptible, progression of infectivity drew up over a period time and proportion
of death rate showed exponential significant digits (Table 1.5).
 I 
Sh = bh − bβ vh v + α h + dh  Sh + ϕ hVh + λ h Rh = T ′ (1.1)
 Nh 
 I 
Vh = α h bh − bβ vh v + α h + dh  Sh + ϕ hVh + λ h Rh = T ′ − n + 1 (1.2)
 N h 
 I 
Eh = bβ vh v − ( vh + dh + c )  Eh = T ′ − n + 1 (1.3)
 Nh 
I h , s = ( 1 − q ) vh Eh − ( dh + φh + δ h + c ) I h , s = T ′ − n + 1 (1.4)
I h , a = qvh Eh − ( dh + φh + δ h + c ) I h , a = T ′ − n + 1 (1.5)
TABLE 1.5
Parameters of Concern for Mathematical Model Construction
Symbol of
Symbols Description Parameters Description
Sh Susceptible population β vh Rate of infectiousness of human

to virus
Sv Susceptible vector population β hv Rate of infectiousness of virus to
human
Eh Exposed latent population(human) b Animal raw food intake
Ev Exposed latent population(vector) bh Recruitment rate into the human
population
I h, a Asymptomatic infectious dh Natural mortality rate in human
population(human)
Iv Infectious vector population dv Natural mortality rate in vector
Rh Recovered from the infection φh Disease-induced death rate in
the human population
Vh Treated or vaccinated vh Disease incubation rate in
human
Nh Total population q Proportion of latent population
who becomes asymptomatic
and infectious
Nv Total vector population δh Recovery rate in human
T ′λ Total transmission population µv Recruitment rate into the vector
Force of infection population
υv Disease incubation rate in vector αh Proportion of susceptible
individuals vaccinated per unit
time
λh Proportion of treated individuals who ϕh Proportion of vaccinated
become susceptible again due to some individuals who lose immunity
accidental cause and become susceptible again
where c is constant parameters.
Rh = δ h ( I h , a + I h , s ) − (δ h + dh ) Rh
 I h,a + I h,s 
Sv = µ v − bβ vh + dv  + I v + Sv
 Nh 
 I h,a + I h,s 
Sv = bβ vh Sv + dv  − ( dv + vv ) EV
 Nh 
All the parameters were subjected to fix the non-negative at initial stage of infection or
conditions ( Sh > 0 ). The model was demonstrated by considering selected parameters that
are showing feasible solutions and lead to uniformly bounded real subsets of Ω. The most
reliable acceptance region at population level is determined by the following equation:
bh
Ω = {(Sh , Vh , Eh , I h , s , I h , a , Rh ) ∈  : N h ≤  T′ − n + 1
dh
µν
Sv Ev I v ∈  : N v ≤ (1.6)
dν
Differentiating the above equation w.r.t. selected parameters and making appropriate sub-
stitutions, we obtain the following equation:
N h = bh − dh N h − ( I h , a + I h , s ) ∅ h ≤ bh − dh N h
Lemma: The real closed set of real subsets Ω is shown to be invariants of positivity of
the solution and attracting all the selected parameters with respect to model building as
described above.
We apply all the real values of subsets derived from the differential in equalities equa-
b
tions (1.15) and (1.16). At initial stage, the model more reliably shows 0 ≤ N h ≤ h and
dh
µv
0 < N v (t ) ≤ as T ′ → ∞.
dv
1.6.2 Endemic and Epidemic Equilibria

As per the standard operating protocol of model building, we extrapolated the disease-
free equilibrium (DFE) E0 and endemic equilibrium E1. They are presented in the follow-
ing equations.
 bh (ϕ n + dh ) bhα h µ 
E0 = ( ShVh Eh I h , a I h , s Rh Sv Ev I v ) =  , , 0, 0, 0, 0 v 0, 0 
 dh (α h + ϕ h + dh ) dh (α h + ϕ h + dh ) dv 
(
E1 = Sh* Vh* Eh* I h , a * I h , s * Rh* Sv * Ev * I v * ) (1.7)
Differentiating w. r. t. “t”, we get the dynamic vector model (DVM).
dSh β hb
= µh ( N h − Sh ) − Sh I v
dt Nh + m
dI h β hb
= Sh I v − ( µ h+γ ) I h
dt Nh + m
dRh
= γ I h − µ h Rh
dt
dS V βV b
= A− Sh I h− µ v Sv
dt Nh + m
dI n βV b
= Sv I h− µ v I v . Global stability and bifurcation were determined in association
dt Nh + m
with the partial differential equation. The Thompson iteration method (scale and shape
parameters were assumed based on the global health index) was used to extract the
real reproduction number (R0) to know the endemism of the nCov. A three-dimensional
dynamic model for HIV infection was proposed by Basavarajaiah et al. (2012) (Figure 1.16).
T ′ = λ − βν ( t ) T ( t ) − dT ( t )
I ′ = βν ( t ) T ( t ) − d1 I ( t )
ν ′ = dh I ( t ) − c v ( t ) (1.8)
The models T ′, I ( t ), and v ( t ) denote the virulence of the virus, the infected cells, and the
free viruses at time “t”, respectively. The constant λ > 0 is the rate at which new uninfected
cells are generated; similarly, d > 0 and β > 0 are the death rates of individuals from infected
cells and rate has progressively increased considering d > 1 and β > 1. The infected cells
produce new viruses at the rate of d1 N during the life of their infection, on average having
the length 1/d1 , where N > 0 is some integer number. The constant c > 0 is the rate at which
the nCov2019 viruses are cleared, and the average life time of a free virus is I/c .
The local stability of endemic and epidemic equilibria was determined by using the
reproductive ratio of the transmission of novel coronavirus derived from model (1.1). The
basic reproduction ratio for model is R0 = ( Nβλ λ0λ1/cdν ), derived with an infection-free
equilibrium E0 = (T0 , 0, 0, d0 ) = ( λ/d0d1 , 0, 0 d1/ν ). If R0 > 1, model 1 is uniquely infected at
(
the equilibrium (susceptible population) E* = T * I *ν * D* . )
λ cv **
T* = −
D Nd ′
cv **
I* =
Nd ′
FIGURE 1.16
Schematic diagram of nCov2019 mathematical model.
c
D* =
Nβ T *
ν =
*
( )
Nβ ( λ1 + λβ1 ) − N 2 β 2 λ2 − λβ12 + 4 Nβ1 β cdν )
(1.9)
2 ββ1 c
From equation (1.9), we simulated the reproduction number R0 from the Thompson itera-
tion method. The susceptible population shows an increasing trend, and the population
does not attain the equilibrium stage due to the rapid multiplication of infective cases
(Figure 1.17). The basic reproduction number of COVID falls in the range 1.5–2, which
is the expected number of secondary cases produced by a single (typical) infection in a
completely susceptible population. It is important to note that R0 is a dimensionless num-
ber and not a rate, which would have units of time. The basic reproduction number, also
called the basic reproduction ratio or the basic reproductive rate, is an epidemiological
metric used to describe the contagiousness or transmissibility of infectious agents. R0 is
affected by numerous biological, social, behavioral, and environmental factors that govern
pathogen transmission and, therefore, is usually estimated with various types of com-
plex mathematical intervention. R0 is not a biological constant for a pathogen or virus, a
rate over time, or a measure of disease severity, and R0 cannot be modified through mass
vaccination campaigns. R0 is rarely measured directly and modeled based on dependent
and independent variable sets. It also solely depends on model structure and its salient
1.2
Yt= 0.000x3 - 0.006x2 + 0.144x; R² = 0.941
1
Susceptible
0.8
P -Value
0.6
Infective
0.4 Recovered
0.2
0
0 5 10 15 20 25 30
Million
FIGURE 1.17
Projection of disease progression by nCoV model.
assumptions (Figure 1.17). It is clearly depicted that more number of susceptible classes
were converted to an infective class because of the rapid outbreak of the virus and the lack
of nursing, palliative, and healthcare facilities (Figure 1.18). Any factor having the potential
to influence the contact rate, including population density, social organization, seasonal-
ity, migration, immigration of the population, and season for vector-borne infection, will
greatly affect the transmission rate of COVID. Because R0 is a function of the effective con-
tact rate, the value of R0 is a function of human social behavior and organization, as well as
the innate biological characteristics of particular pathogens. Varied R0 values (range 5–10)
were reported for MERS and SARS diseases in a variety of areas and periods (WHO and
CDC). This wide range highlights the potential variability in the value of reproduction
number for an infectious disease event on the basis of local socio-behavioral and environ-
mental circumstances. The prevention measures and newer healthcare policy interven-
tions reduce the proportion of population at risk of infection and have been proven to be
FIGURE 1.18
Transmission rate of novel coronavirus 2019.
highly effective in mitigating future outbreaks. This conclusive description is sometimes

used to suggest that the aim of vaccination and quarantine campaigns is to decline the
susceptible population and also reduce the R0 value (R0 < 1). The removal of susceptible
population significantly affects the infection transmission mechanism by reducing the
number of effective contacts between infectious and susceptible cases.
1.7 Model Discussion
COVID-19, which is caused by the subtypes of SARS and MERS viruses causes illnesses
such as severe pneumonia and ADRS in humans. Siming et al. (2017) studied a novel
dynamic model describing the spread of the MERS and the expression of dipeptidyl
peptidase 4, demonstrating a new dynamic model with the inclusion of ten param-
eters. The study showed that the infection-free equilibrium E0 is asymptotically stable
( E0 = 20, 0, 09.0909 ) and R0 = 0.909 < 1, and also the fitted model describes the interven-
tion of transmission and prevention mechanisms for curbing MERS at global level. All
the parameters included for the demonstration are found to be significantly different in
the orbit of the fitted model at initial conditions; further, the fitted model showed that
the infection-free endemic equilibrium E* is asymptotically stable at initial conditions.
Later, the infection rate rapidly increases due to the addition of susceptible population
spreading the diseases at unexposed sites (population would be full blown E* >1; R0 > 1).
A similar intervention model was demonstrated by Zhao et al., (2014), Rogers (2016),
Mille et al., (2014) and Nowak et al., (2000). Basavarajaiah et al. (2012) fitted a mathemati-
cal model approach to HIV/AIDS transmission from mother to child. As per the fitted
model, they concluded that the mathematical model will help clinicians and research-
ers understand its anticipated spread in a variety of population settings. The findings
clearly envisage that the disease-free equilibrium (DFE) and the endemic free equilib-
rium ( EFE ) were locally asymptotic stable ( R0 < 1) at orbital conditions of the popula-
tion (early screening). At the later stage, the diseases became endemic due to vertical
transmission (HIV transmission from mother to child). The present research findings
revealed that the COVID-19 virus is more virulent and transmits the infection through
infected vectors rapidly, such as through touching, hugging, sneezing, infected drop-
lets spread through air, usage of toilets, sharing of common articles, kissing, frequent
rubbing of nose and eyes without personal hygiene, common transportation, migration
from one place to another, exposure to mass or public places, and sharing of injecting
drug needles. The models T ′, I ( t ) and v ( t ) are vulnerable at the defined state of trans-
mission (the infected cells and free viruses at time “t”, respectively). The disease-free
equilibrium ( DFE ) E0 was shown to be asymptotically stable and endemic in nature E1 > 1.
( )
E1 = Sh* Vh* Eh* I h , a * I h , s * Rh* Sv * Ev * I v * becomes a full-blown population in epidemic sites with
R0 = 1.5 to 2 (Figure 1.7) since the mortality rate was a very small number ( d1 < 1) due to
the prevention programs undertaken at global level. Chowell et al. (2016), Man Li et al.
(2016), Mc. Cluskey et al. (2010), Huang et al. (2009), Li W F et al. (2015), Saito et al. (1999), and
Qin Y X et al. (1981) demonstrated dynamic models and stability analyses in a variety
of settings. Finally, the above-cited research works conclude that the basic reproduction
number is an indicator to describe the well-being of the selected biological parameters
to solve the real-world problems of our objective of interest. From an analytical point of
view, we determined the basic reproduction number R0 and investigated the existence and
stability equilibria (equation 1.2). The disease-free equilibrium E0 coexists between two
endemic equilibria E1 & E2 . These results indicate that forward and backward bifurca-
tions may occur in the system (Figure 1.18). It is found that the disease mortality rate plays
a significant role in the occurrence of backward bifurcation. As we know, the existence
of backward bifurcation means that the disease cannot be eradicated by simply reducing
the value of reproduction number R0 < 1. In this intervention, the mortality rate is also the
threshold for eradicating SARS-Cov-19 (Diekmann et al. 1990; Vanden Driessche et al., 2002;
Garba et al., 2013; Castillo Chavez et al., 2004). It is possible that increasing awareness,
proper vaccination, and effective quarantine may effectively reduce the reproduction
number. However, at the same time, we find the recruitment rate in the vector population
( µ ), the disease incubation rate in the vector population (vv ), the rate of infectiousness
of human to virus ( β vh ), and the rate of infectiousness of virus to human (β hv ) may be
effective in reducing the reproduction number and mortality rate. The global stability of
equilibria is one of the most difficult problems that stabilize the susceptible population
(Sh) and infective population in any infectious dynamic model, and it is essential in ruling
out the scenarios such as periodic solution. The model findings showed that the infected
( )
population is in an unstable endemic equilibrium E* , R0 > 1; E1 > 1; E2 > 1 (Koella, 1991;
Chitnis et al., 2006; Buonomo et al., 2013; Chitnis et al., 2008) (Figures 1.19 and 1.20).
1.7.1 Model Conclusions
The overall output of the model concluded that the reproduction number R0 of COVID
rapidly outbreaks at the global level and is in the range of 1.5–2.0, indicating that suscep-
tibility and infectivity rate of disease are rapidly increasing (unstable E* > 1). Our fitted
mathematical model of COVID-19 reproduces the long-term persistence of transmission
to the human population, and more genetic-based microstudies are required to identify
the pathogenesis of vector population for early intervention of therapeutic and underlying
preventive measures at the population level (screening of causal agent at an early stage).
Our fitted model will help policy makers, healthcare specialists, and research beginners
in taking the right decisions at the right time for curbing the spread of SARS-Cov-19 at
global level.
FIGURE 1.19
Geometric progression of estimated COVID cases.
FIGURE 1.20
Trend of deaths estimated using the mathematical model.
1.8 Epidemiological Model for the Estimation of Hazard

Rate and Geometric Progression of nCov2019
The epidemiological triangle or triad is the traditional model of infectious diseases causa-
tion. Diseases are the result of forces within the dynamic system consisting of three com-
ponents: (i) an external agent, (ii) a susceptible host, and (iii) an environment that brings
the host and agent together (Figure 1.10). The transmission occurs in many ways.
• Direct contact—physical contact with body parts of an infected person, such as

touching, kissing, biting, and sex.
• Direct way of transmission —projection of saliva droplets while coughing and spitting.
• Transplacental transmission—transmission from mother to child through the
placenta, e.g., HIV.
An epidemiological triangle describes that the interaction of an agent and host in an appro-
priate environment results in statistical modeling, which describes the distribution and mag-
nitude of health and disease problems in human population. The epidemiological modeling
correlates the etiological risk factors in the pathogenesis of disease conditions. Fedorov et al.
(1993) described the rationality of EPM in many infectious diseases. One of the important
controlling factors of EPM is to provide the data sets from the affected sites or outbreaks. It is
very essential to plan, implement, and evaluate the services for the prevention, control, and
treatment of diseases. Hulley et al. (2001) described that EPM eliminates the health problems
of community and provides the health and well-being of society as a whole. The novel coro-
navirus 2019 (COVID) is a debilitating virus (CDC Website, 2022b) and causes viral respira-
tory illness; it is highly virulent. Epidemiological and mathematical interventions are very
important to describe the disease transmission and draw preventive measures at global level.
In the advent of health emergency, we have developed epidemiological and statistical models
to measure the geometric progression rate at global level considering the triangular form of
epidemiological parameters—the pathogenic agent, environment, and host. In the interven-
tion, we also consider the formulation of the model. The statistical modeling is a modern tool
kit that helps epidemiologists measure the exposure and outcomes of diseases, but the science
of epidemiology has improved a lot from the notation and explores the causal relationship
between the various outcomes driven by the risk factors and causative agents (Figure 1.10).
Pathogenesis depends on too many factors such as toxicity, virulence, infectivity, and virus
susceptibility to survive outside body. Although, toxicity is the major impaired factor that
signifies the degree of harm and toxicants that it can cause. “The dose makes the poison”
toxicity depends on the combined effect of chemical and its quantity; it is analogous to patho-
genesis or virulence of the virus, and the degree of harmful biological hazard that spreads the
COVID. The etiology and toxicity are positively associated for spreading the infection; COVID
may possibly be connected to zoonotic or environmental exposure to the seafood (toxic sea-
food) market in Wuhan (WHO, 2020). As per the CDC (2022b) report, four major categories or
genera of coronavirus exist. They are known by the Greek letters α , β , δ , and γ . Only α and β
coronaviruses are known to infect people. These viruses spread through the air, and just four
types (229E, NL63, OC43, and HKU1) are solely responsible for 10%–40% of colds around the
world. Coronavirus is only loosely enshrined in its deoxyribonucleic acid (DNA).The corona-
virus designation is less about the genetics and more about the way it appears under a micro-
scope. Prof Brent C Satterfield, the co-founder and chief scientific officer of Co-Diagnostics,
a company based in Salt Lake City, Utah, and Gujarat, India, is developing molecular tests
for diagnosing SARS-Cov-19 infections. The genetic makeup of coronavirus is composed of
a single-stranded RNA (Figure 1.10), a chemical cousin of DNA. Viruses in the family are
often not very similar at the genetic level or composition, with some types showing more dif-
ferences between them than humans. The new SARS-Cov-19 proteins are between 70% and
99% identical to their counterparts in the SARS virus (WHO, 2020). Presently, SARS-Cov-19 is
expressed to be less virulent with about 4% mortality rate. But that number is still a moving
target as more cases are diagnosed (Chinese Research Academy). The source of SARS-Cov-19
is still in a dilemma. CDC reported that bats are often thought of as a direct source of coro-
navirus in humans. SARS probably first jumped from raccoon dogs or palm civets before
making the leap to humans. All the pieces are necessary to reactivate and create SARS that
are circulating among bats, although that virus has not been seen since 2004. The statistical
modeling of SARS-Cov-19 addresses the salient importance of data quality and provides a
discussion on causality in the context of SARS-Cov-19 epidemiological studies. One of the
objectives of epidemiological studies or modeling is to evaluate the objective of our research
hypothesis scientifically and statistical consideration regarding disease etiology, host, and
environmental factors. A valid statistical inference is the process of drawing implied conclu-
sion that is based on the population or sampled data sets, and also the statistical hypothesis
testing is the procedure mostly used to accomplish that. Many statisticians argue that judicial
limits (CI 95% or CI 99%) should be used over hypothesis testing to draw a valid inference
about the population by providing a measure of uncertainty for the estimation of parameters.
They are better suited to determine the clinical and therapeutic importance. In this context,
the present study aims to build epidemiological and statistical modeling for the benefit of
hypothesis testing of SARS-Cov-19 at early and advance stages of infection considering many
attributes and risk factors (Figures 1.21 and 1.22).
1.8.1 Formulation of the Epidemiological Risk Assessment COVID Model

The random variables X1,X2, X3…Xn are extracted from the pathogen agent and environ-
mental and host factors. Each factor is very important to know the hazard risk of the novel
coronavirus 2019. The parameters were modeled using the following equation.
Yt = α i + β 0 x0 + β1 x1 + β 2 x2 …β n xn (1.10)
FIGURE 1.21
Forward and backward bifurcations of novel coronavirus 2019.
FIGURE 1.22
Disease-free endemic equilibrium.
where Yt = the response variable , α = intercept, and β 0 , β1 ,…β n xn are the slope of the curve
of X1, X2, X3 …Xn coefficients.
(
Yt = α i β j xn ) Where i = 1,2 k j = 1,2 m and x = 1,2 n (1.11)
In equation (1.2), α i , β j are real-valued constants determined by solving the normal equation
t
∑ log Y = N log α + log β ∑ x

i−1
t (1.12)
∑X log Y = log α ∑ X + log β ∑ x

i−1
t
2
(1.13)
xn is from the midpoint of the time variable “t” from equation (1.3). Then we solve
n n
∑ ∑
log Y X logY
log α = and log β =
i=1
N i=1 ∑X 2
The second-degree exponential in the order of equation (1.3) becomes the following:
2
Yt = ab xn c xn (1.14)
After antilog substitution, equation (1.5) becomes
Yt =  log α + xn log β + xn2 log c  (1.15)

log α = 
∑ log y − log c∑ x 2 

 N 
 
log β =
∑ x log y
∑x 2
log c =
∑ x log Y − log α ∑ x
2 2
(1.16)
∑ xy
nCov2019 epidemiological growth is simulated by using equation (1.16).
yt = kα β x where “k” is a constant at the highest point of transmission over a period of
time.
1
= k + α βx (1.17)
yt
k
Yt = (1.18)
1 + eα i + β0 x0 + β1x1 + β2 x2…βnxn
Consider a complex mode with more than one predictor, X1, X2, X3…Xn. The Cox propor-
tional hazards model is
h ( t ) = h0 ( t ) exp (α i + β 0 x0 + β1 x1 + β 2 x2 …β n xn ) (1.19)
Suppose we wish to compare two participants in terms of their expected hazards. The first
has X1 = a, and the second has X1 = b. The expected hazard h(t) is equal to h0(t) exp (b1a) and
h(t) = h0(t) exp (b1b), respectively. The hazard ratio of these two expected hazards is h0 (t)
exp (b1a)/ h0 (t) exp (b1b) = exp (b1(a−b)), which does not depend on time t. Thus, the hazard is
proportional to time.
 h (t ) 
  = exp (α i + β 0 x0 + β1 x1 + β 2 x2 …β n xn ) (1.20)
 h0 ( t ) 
Sometimes, the model is expressed differently, relating to the relative hazard, which is the
ratio of the hazard at time t to the baseline hazard, to the risk factors.
 h (t ) 
ln   = exp (α i + β 0 x0 + β1x1 + β 2 x2 …β n xn ) (1.21)
 h0 ( t ) 
In equation (1.10), we can take natural logarithm (ln) on both sides of the Cox proportional
hazards regression model to produce the following which relates to the log of the relative
hazard to a linear function of the predictors. Notice that the right-hand side of the equation
looks more familiar to the linear combination of the predictors or risk factors (as seen in
the multiple linear regression model).
 h (t ) 
From equation (1.11), we assume that f (t) =  
 h0 ( t ) 
f (t ) = α (1 + βn )
t
(1.22)
Α is the initial growth and βn is the rate of change of growth of novel coronavirus at nth
region.
α > 0 and β n > 0 growth takes place at time “t”
f ( t ) = P, P0 − initial population
( )
t
P = P0 * e 1+ β0 x0 + β1x1 + β2 x2…βnxn (1.23)
( )P
t
Pn = Pn−1 * e 1+ β0 x0 + β1x1 + β2 x2…βnxn 0 is initial stage, disease change at nth time
( )
t
Pn = Pn−1 * e 1+ r
 P − Pn−1 
r = e n (1.24)
 Pn−1 
Here, e is the Euler number and is 2.71, and “r” is the rate change of novel coronavirus 2019
growth rate at time “t”.
We consider the number of people infected with respect to time period. The rate of
change of growth can take place as follows:
∂N
= r ⋅ dt
N
∂N
∫ N
= r ⋅ dt
ln N = rt + c
When t = 0, N = N0; therefore, c = ln N0.
ln N = rt + ln N 0
ln N − ln N 0 = rt
ln N
ln N − ln N 0 =
ln N 0
ln N
= rt
ln N 0
N
= e rt
N0
N = N 0 e rt (1.25)
N = 2 N 0 ; so that
2 N 0 = N 0 e rt
2N0
= e rt
N0
2 = e rt
ln 2 = e rt
ln 2
= t ; t is always equal to doubling time (1.26)
r
Table 1.6 depicts the confirmed cases of COVID-19 ARD reported by different provinces,
regions, and cities in China. As per the metadata, the highest infected figure was seen in
China at the initial stage 33,366 (23.36%); suspected cases 11,295 (7.90%) confirmed cases
reported in Hubei region (epicentric zone) and death toll 1,068 (2.38) with case fatality
rate >10%. A total of 44,730 (31.31%), suspected 16,067 (11.25) and mortality was <5% 1,114
(2.49%) recorded in the various provinces, regions, and cities in China.
TABLE 1.6
Confirmed Cases of COVID ARD Reported by Different Provinces, Regions, and Cities in China
(Base Data in Epicentric Zone)
Province/Region/City Population (in 10,000) Confirmed Cases Suspected Cases Total Deaths
Hubei 5,917(4.13%) 33,366(23.36%) 11,295(7.908%) 1,068(2.389%)
Guangdong 11,346(7.94%) 1,219(0.85%) 135(0.095%) 1(0.002%)
Zhejiang 5,737(4.01%) 1,131(0.792%) 263(0.184%) 0(0.000%)
Henan 9,605(6.72%) 1,135(0.795%) 538(0.377%) 8(0.018%)
Hunan 6,899(4.83%) 946(0.662%) 135(0.095%) 2(0.004%)
Anhui 6,324(4.42%) 889(0.622%) 79(0.055%) 4(0.009%)
Jiangxi 4,648(3.25%) 844(0.591%) 155(0.109%) 1(0.002%)
Chongqing 8,051(5.63%) 543(0.380%) 62(0.043%) 0(0.00%)
Shandong 3,102(2.17%) 505(0.354%) 428(0.300%) 3(0.007%)
Sichuan 10,047(7.03%) 497(0.348%) 71(0.050%) 1(0.002%)
Heilongjiang 8,341(5.84%) 436(0.305%) 432(0.302%) 1(0.002%)
Beijing 3,773(2.64%) 378(0.265%) 171(0.120%) 8(0.018%)
Shanghai 2,154(1.50%) 352(0.246%) 218(0.153%) 3(0.007%)
Fujian 2,424(1.69%) 306(0.214%) 177(0.124%) 1(0.002%)
Hebei 3,941(2.75%) 272(0.190%) 74(0.052%) 0(0.00%)
Shaanxi 7,556(5.29%) 251(0.176%) 43(0.030%) 2(0.004%)
Guangxi 3,864(2.70%) 225(0.158%) 367(0.257%) 0(0.00%)
Yunnan 4,926(3.44%) 222(0.155%) 248(0.174%) 1(0.002%)
Hainan 4,830(3.38%) 154(0.108%) 89(0.062%) 0(0.00%)
Shanxi 934(0.65%) 145(0.102%) 206(0.144%) 3(0.007%)
Guizhou 3,718(2.60%) 124(0.087%) 65(0.046%) 0(0.00%)
Liaoning 3,600(2.52%) 131(0.092%) 53(0.037%) 1(0.002%)
Tianjin 4,359(3.05%) 111(0.078%) 287(0.201%) 0(0.00%)
Gansu 1,560(1.09%) 106(0.074%) 328(0.230%) 2(0.004%)
Jilin 2,637(1.84%) 86(0.060%) 18(0.013%) 2(0.004%)
Inner Mongolia 2,704(1.89%) 83(0.058%) 57(0.040%) 1(0.002%)
Xinjiang 2,534(1.77%) 60(0.042%) 11(0.008%) 0(0.00%)
Ningxia 2,487(1.74%) 59(0.041%) 31(0.022%) 0(0.00%)
Ningxia 688(0.48%) 58(0.041%) 31(0.022%) 0(0.00%)
Hong Kong SAR 745(0.52%) 49(0.034%) 0(0.00%) 1(0.002%)
Qinghai 603(0.42%) 18(0.013%) 0(0.00%) 0(0.00%)
Taipei and Environs 2,359(1.65%) 18(0.013%) 0(0.00%) 0(0.00%)
Macao SAR 66(0.04%) 10(0.007%) 0(0.00%) 0(0.00%)
Xizang 344(0.241%) 1(0.001%) 0(0.00%) 0(0.00%)
Total 142,823(100%) 44,730(31.31%) 16,067(11.25%) 1,114(2.49%)
Source: Data as reported on February 12, 2020, by WHO, NBSC China (not cumulative figure).
From equation (1.26), the simulated number of persons infected per 100,000 over a period
of time with a lag of 2 years was assumed to be formulated in the model. The model finds
that a total of 30,000 cases were infected per 100,000 at the probability value (p = 0.00007,
R 2 = 0.987). Our fitted model is shown to be significantly correlated (Figure 1.23) to disease
distribution status simulated at global level (WHO, 2020) (Figure 1.24).
From equations (1.24) and (1.25), we simulate that the number of suspected cases per 100,000
at defined time period “t” with a lag of 2 years was assumed to be formulated in the model.
The model finds that a total of 12,000 cases were suspected and found in the various provinces
of China per 100,000 at the probability value (p = 0.0002, R2 = 0.982). The present demonstrated
model was found to be significantly correlated (Figure 1.25) on disease distribution. The sus-
pected cases suffer from devastating COVID virus and our model results yield similar results
generated at a global level from the Chinese Health Authority and WHO (WHO, 2020).
From equations (1.24) and (1.25), we simulated the number of death cases per 100,000 at
defined time period “t” using Poisson distribution model. The model finds that a total of
11,000 death events were found in various provinces of China per 100,000 at the probability
value (p = 0.99, R2 = 0.99) (Table 1.2). The statistical figure shows countries, territories, and
areas with reported and confirmed COVID-19 cases and deaths by February 12, 2020 (WHO).
A total of 45,612 cases were confirmed worldwide. The incidence was more in Western Pacific
Region such as China 45,171 (new cases were 2022), Singapore 47 (0.10%), Japan 28 (0.06%),
Republic of Korea 28 (0.06%), Malaysia 18 (0.039%), Australia 15 (0.032%), Vietnam 15 (0.032%),
Agent pathogen Environment Host Management Policy
Characteristics Characteristics Characteristics

Toxicity (x1) Climate (X1) Age(x1)
Virulence (x2) Physical structure (x2) Prior exposure(x2)

Intervention
Infectivity (x3) Population density(x3) Susceptibility(x3)
Protect(x1) Intervention
Susceptibility to survive Social structure(x4) Co-infection(x4)
Educate(x2) Educate
outside body(x4) (x1),
Intervention Immune response(x5)
After change
Intervention
exposure(x3 ) Housing quality(x1) activity Intervention
Eradicate and (x2)
genetically modify (X1) Sanitation, water (x2) Treat, isolate(x1)
Prevention services(x3) Immunize(x2)
Nutrition(x3)
FIGURE 1.23
Epidemiology of SARS-Cov-19 flowchart.
FIGURE 1.24
Simulation figure for the number of persons infected per 100,000.
FIGURE 1.25
Projected death cases of SARS-CoV-2 per 100,000.
Philippines 3 (0.006%), and Cambodia 1 (0.002%). An overall prevalence was 31.73% (con-
firmed); Southeast region: Thailand 33 (0.072%), only one case was confirmed in Nepal
and Sri Lanka; Region of America: the USA 13 (0.028%) and Canada 7 (0.015%) cases were
confirmed; European region: Germany 16 (0.035%), France 11 (0.024%), the UK 8 (0.017%),
Russian Federation 2 (0.0043%), Spain 2 (0.0043%), Belgium, Finland and only one case was
found to be confirmed in Sweden; Eastern Mediterranean region: United Arab Emirates 8
(0.017%)cases were confirmed and international conveyance (Japan) 175 (0.383%) cases were
confirmed with 40 new cases (Figure 1.26 and Table 1.3). The death toll was higher in China
with 1113 cases (2.43%). The mortality is higher in Wuhan (4.90%) and lower in the rest of
China (2.10%). It is even lower outside China (0.20%). As per the CDC literature on under-
standing of the virus, the disease is still evolving worldwide. The virus can spread through
droplets released while coughing that can be breathed in or by touching infected surfaces.
1.2
Yt= 0.000x - 0.001; R² = 0.999
1
0.8
0.6
P-Value
0.4
0.2 PD Linear (PD)
0
-200 0 200 400 600 800 1000 1200
-0.2
Deaths
FIGURE 1.26
Simulation of the expected number of infected cases in WHO region.
This virus deleteriously affects the respiratory system. Approximately >75,000 people have
been reported to be infected; this COVID-19 has already spread widely, with 99% of cases
in China (Figure 1.14). How efficiently the virus is transmitted from one person to another
is not fully understood yet (CDC, 2021b). Therefore, it is very difficult to make epidemio-
logical forecasts.
1.9 Epidemiological Model Approach of New Diseases

The essence of epidemiological models has awfully aided in the understanding of risk associ-
ated with the global spread of COVID-19 contagious disease. The complexity of containing
this pandemic that spreads easily between humans has steadily grown with the ease of global
travel and closer connection between countries. As humans find faster ways to move from
one place to another (migration or travel) and engage in their work, the opportunities for dis-
eases to acquire or contain, and result in pandemics, increase as pathogens were introduced
to completely susceptible populations (Colizza et al., 2006; Balcan et al., 2009). Epidemiological
modeling attempts to describe the understanding of the risks associated with the spread of
infectious diseases (COVID-19). For instance, the model could predict the chance that a dis-
ease will invade a particular pathogen, host, and environmental condition with respect to
different geographical regions. The model will also describe the expected number of cases
within a particular frame or the expected effect of intervention. For this information to be of
value, the model must be a sufficiently accurate representation of reality (true information)
in order to provide useful inputs to the researchers, epidemiologists, and policy makers. The
present model will serve as a trade-off between complexity and accuracy at an end point of
the research and will also be most appropriate for health policy makers and health special-
ists to draw the right decision at the right time triggered from the analytical interventions.
According to Balcan et al. (2010), Keeling and Rohani (2008), and Landry et al. (1983), a good
model should both have suited traits purpose and be parameterizable by existing life data
sets. Deciding which epidemiological models to use is an important decision for research-
ers (Mateus et al., 2014; Morens and Fauci, 2013; Arino and Portet, 2015) as the evaluation of
a model generates subjective measures of usefulness and their practicability. In the context
of practicability and theoretical approach for the effective prediction of COVID-19, we dem-
onstrate the various epidemiological models in order to address the common approach and
global epidemic trend and identify any analytical and preventive research gaps for future
research. We focus on identifying the state of the model and the growth rate of COVID at
population level determined from base population. It is useful at this point at global level to
reflect that epidemiological modeling of COVID-19 is a formidable tool for taking right deci-
sions and policy implementations at global level without any prejudice.
1.9.1 Model Formulation
The hazards regression model was simulated from the following equations
p( x) p( x)
h (t ) = = (1.27)
s ( x ) 1 − D( x)
h ( t ) = h0 ( t ) exp ( β1 X 1 + β 2 X 2 + β 3 X 3  β n X n ) (1.28)
( t ) = h0 ( t ) exp ( β1X1 + β 2 X 2 + β 3 X 3 …β n X n )
h
h (t )  1 
= (1.29)
h0 ( t )  1 + e − a + β1 X 1 + β 2 X 2 + β 3 X 3  β n X n 
 h (t ) 
ln   = a + β1 X 1 + β 2 X 2 + β 3 X 3  β n X n Odd ratio
 1 − h0 ( t ) 
Yt = α i + β 0 x0 + β1 x1 + β 2 x2 …β n xn + n

 Y11   α 11   β   11 
11
     X 11 X 12 X 13     
 Y12 =  α 12 + ↓  X   β 12   12 
     21 X 22 X 23  * 
 ↓ + 
(1.30)
     X 31 X 32 X 33     
 Y1n   α 1 k     β   11 
 1j 
Equation (1.23) describes the generalized method for the extrapolation of coefficient of
novel coronavirus subjected to slopes, designed in multivariate analysis. From equation
(1.21), we have simulated the likelihood parameters of unknown parameters.
1
htθ ( x ) = ( − β1X1 + β2 X2 + β3X3βnXn )
1+ e
(
htθ ( x ) = g θ iT xi )
where g ( Z ) = θ iT xi
1 ez
h(Z) = −z
=
1+ e 1 + ez
exp z
= ( exp z )( 1 + exp z )
−z
if h ( Z ) =
1 + ez
exp z
= ( exp z )( 1 + exp z ) + (exp z) ( −1) ( 1 + exp z ) ( exp z )
−z −2
h′ ( Z ) =
1 + e− z
( exp z )(1 + exp z ) − ( exp z )2

(1 + exp z )2 (1 + exp z )2
h′(Z) = h ( z ) ( 1 − h( z)) (1.31)
1.9.1.1 Latent growth model of novel coronavirus

The latent growth model (Figure 1.27) is a newer technique or statistical measure used
in the structural equation modeling (SEM) framework to estimate the disease epidemic
trajectories (Bijleveld et al., 1998; Bollen and Curran, 2006; Muthén and Muthén, 2000). It is
one of the longitudinal analytical techniques used to estimate the growth rate of a disease
over a period of time “t”. Individual intercept and slope of the random variables were
extracted from the binary logistic or generalized regression linear model and correlated
with the slopes or coefficient with defined time intervals (baseline and months or days of
infection from the outbreak to latent period of infection) (Figures 1.28 and 1.29).
1.9.2 Gauss–Markov Theorem (GMT)

The ordinary least squares (OLS) analysis or estimation is the best linear unbiased estima-
tion (BLUE). Under the following salient assumptions, we can prove the Gauss–Markov
Dec 2019 Jan 2020 Feb 2020 March 2020

Base line 0 1 2 3
..
..
..
.
Intercepts
Slopes
FIGURE 1.27
Simulation figure for the number of COVID-induced deaths per 100,000.
X1 X2 X3
rxy rxy rxy
Y1 Y2 Y3
FIGURE 1.28
Latent effect of growth model plan.
0.00025
Yt = -2E-0ln(x) + 0.000 ;R² = 0.781
0.0002
ND Log. (ND)
0.00015
0.0001
0.00005
-2000 0 2000 4000 6000 8000 10000 12000
FIGURE 1.29
Cross-lagged growth model design.
theorem (GMT) by using equation (6.8). Importantly, we consider the analytical interven-
tion to prove the Gauss–Markov theorem at population level (Figure 1.30).
• Linearity in parameters—all parameters are linearly related, Y = α + β 1X 1 + u.

• The random sampling of “n” observations ( X i , Yi ) ; i = 1, 2, n.
• Sampling variations would be self-explanatory of X i, and all the estimated values
are not the same, X i ≠ ( X i = xI , x2  xn ).
 u
• The zero conditional mean—the error “u” is expected to be zero, E   = 0 .
 x
• Homoscedasticity—the errors have shown the same variance forgiven values of
 u
the explanatory variables, Var   = σ 2 .
 x
1.2
1
Probability values
0.8
0.6
0.4
0.2
0
0 5 10 15 20 25
10 millions 20 millions 30 millions 40 millions
FIGURE 1.30
Simulation of the trend of coronavirus outbreak in China.
NOTE: Homoscedasticity, similar or identical distribution, normally distributed

( )
X ij ~ N µ , σ 2 , are independent and uncorrelated.
From equation (6.8), we estimate βj = CkxnY => βj is the linear estimators of “Y”.
Let C = ( X ′X ) X ′ + Dkxn and ρ ( D ) = k.
−1
Then, estimate
βj = ( X ′X ) X ′ + D  [ Xβ + u]
−1
= β +  X 1 X −1 X ′ u] + DXβ + Du 
( )
E βj = β + DXβ = [ lk + DX ] β (1.32)
This theorem is very important for the estimation of likelihood parameters, because it fol-
lows estimating the even form of weak set of assumptions and hence does not require
assumptions of shape parameters of the distribution, which precludes the error term. In the
matter of interpretation of likelihood, this theorem is more favorable and gives consistent
estimated values from machine learning. We consider βj , the least squares estimator of β .
From equation (6.9), we obtain it using the linear estimator techniques because they are
very easy to compile and the concept of estimators can be easily understood. We restrict
ourselves even further, as shown in Figure 6.2. Within this set of linear estimators, we con-
sider only the limited class of weights assigned for prediction; parameter is unbiased. The
Gauss–Markov theorem has an interesting corollary for the estimation of unknown param-
eters considering massive data. As a special case of regression model, we can ask what
happens if we explain Y, but βj = 0 so that no independent variables “x” will come into play.
NO T E : All equations have been derived for the estimation of likelihood by using machine
learning. The embedded equation will emphasize that the GMT is very much restricted in
applying only to estimator that is both linear and unbiased. It follows that there may be
biased or nonlinear estimator that is better (smaller variance) than the least squares esti-
mator (LSE). The confidence intervals and testing hypothesis are about “β”. By using vari-
ance and mean, we have determined the Z-values; the condition of normality of estimator
“β” is now in order. First, standardizing “β”, we obtain “Z”.
βˆ − β
Z= (1.33)
σ2 ∑ X i2
where “Z” is normally distributed, Z ~ N ( 0,1), i.e., “Z” is normally distributed with mean
and variance. Since the variance of “Y” is generally unknown, it was estimated from
equation (6.11).
n
1
∑(Y − Yˆ )
2
S2 = i i (1.34)
n i=1
where Ŷi is the fitted value of “Y” on the estimated regression line, that is
Yˆ = αˆ + β X i (1.35)
We have tested the hypothesis on sampled observations using t tests.
βˆ − β
tα = 0.05 = ~ ( n − 2 ) df (1.36)
2
S / ∑X 2
i
Let tα =0.05 denote the “t” value that leaves half of the distribution in the upper tail, that is
Pr ( −tα =.025 < t value < tα =.025 ) (1.37)
Substituting from the above equation, we obtain the following equation:
 
 βˆ − β 
Pr  −tα =.025 < < tα =.025  = .95 (1.38)


S / 2
∑X 2
i


The inequalities within the bracket may be expressed as
   
 S   S 
Pr  β − tα =.025  < β <  β + tα =.025  = .95

 ∑ Xi 2 


 ∑ Xi 2 

which yields the 95% confidence intervals for slope “β”.
S
β = β ± tα =.025 ~ ( n − 2 ) df (1.39)
∑ X 2i
a
+ 1 1 1 1
RR = a
c { }
b , SE ln ( RR ) = + − −
a c a+b c+d
c+d
CI ( 95% ) = exp ( ln ( RR ) − 1.96*SE ln(RR )  to exp ( ln ( RR ) + 1.96*SE ln ( RR ))
The COVID data sets were analyzed using 2 × 2 contingency table (compared with the pos-
itive and negative numbers in association with the exposed and unexposed population).
The results show that the relative risk ratio was 0.15 (CI 100%), which is less than unity
(R < 1) (Table 1.7). This would suggest that the exposure being considered is in association
with a reduction in risk. In this present study, confirmed COVID cases who underwent
incidental exposure to the treatment had 1.5 times the risk of death and, in case of geriatric
population (65–85 years; IQR 62–83 years), the risk of death was 10.56% times higher (sur-
vivability very less), with highest specificity (85%), sensitivity (93%), NPV (71%), and PPV
(81.33%), and it was found to be statistically significant (p = 0.0001) (Table 1.8).
TABLE 1.7
Relative Risk of COVID-19 (First Wave)
Relative risk (risk ratio) 1.526
100% Confidence interval [0.153, 0.153]
100% Left-sided interval [0.153, +∞]
100% Right-sided interval [−∞, 0.153]
P-value 0.000
Z-score 39.275216
Number needed to be treated (benefit) 2.216
100% NNT confidence interval [2.216, 2.216]
TABLE 1.8
Relative Risk (RR) Measured by the SE and 95% CI (The Formula for the Determination of RR)
Criteria Exposed Unexposed Total
No. of positives a b a+b
No. of negatives c d c+d
Total a+c b+d N
1.9.3 Maximum Likelihood Estimation (MLE) of Gauss–Markov Theorem (GMT)

The Gauss–Markov theorem (GMT) indicates the overall justification of least squares
analysis. The selected parameters shall not require any salient assumptions of Gaussianity
(estimation of normality of the error). In this section, the normality assumptions are made
only for small sample estimation and this is due to some quite general principles that are
adopted for the estimation of likelihood; that is, small sample estimation will require lim-
ited observations and it should be normally distributed with parental population to validate
the t-distribution status. We make strong assumptions for testing “t”. On this paradigm,
we derive maximum likelihood estimation (MLE) of various parameters of intercepts and
slopes of the curve (coefficients) on the distinct variables. The MLE techniques have been
involved with various possible speculated populations for the estimation of error rate. Our
question is how likelihood estimation is accepted in each of the samples giving rise to the
estimation of sampling errors and also the observed values are geometrically progressed.
In the cited problem, we will be able to resolve the research gap by using GMT for testing
the null hypothesis at sample level (by moving the regression line and its surrounding
distribution through all possible positions in each space of random variable). Moving the
regression line from intercept to another state of the random variable, the results were
fascinatingly simulated with the likelihood function on each point of the variable of our
interest. Let us consider that L (Y1 , Y2 …Yn ) is the likelihood or probability density function
of the sampled observations, which can be expressed as a function of all possible popula-
tion values of α , β , and σ 2 . First, we formulate the probability distribution with density
function (PD) of the first value of “Y”, which was derived from the following equation.
 1 
1 –
 2σ 2 
[Yi −α + β Xi ]2
L (Y1 , Y2 …Yn ) = exp o (1.40)
2 πσ 2
n   1 
Y −α + β Xi ] 
2 [ i
2
∏
1 –
L (Y1 , Y2 …Yn ) =  exp o  2σ   (1.41)
i=1  2 πσ 2 
Recall that the observed Ys are given. We speculated on the various values of α , β , and σ 2
to emphasize equations (6.16) and (6.17).
 1 
1 [Yi −α + β Xi ]2
( )
–
 2σ 2 
L α , β ,σ 2 = exp o (1.42)
( 2πσ ) 2 n/2
The value of α , β will make “L” have largest values. The only place α and β appear as the
exponent is equation (1.41); moreover, we maximize the function with negative exponent
by minimizing the largest magnitude of the exponent. Since we designate equation (6.18)
for the estimation of ML, our estimation α̂ and β̂ is used to minimizing the function of
family of errors.
∑ {Y − αˆ − βˆ X }
2
minimize i i (1.43)
Differentiating equation (1.43) w.r.t. x, we will get accurate values.

1.9.4 Gauss–Markov Weighted Least Squares Analysis

In any type of research pedagogy, greater errors occur due to sampling and non-sampling
methods; thus, observations give a very less precise indication (precisions is very less) for
the estimation of true errors (where the true or accurate lies or fitted). Therefore, it is very
reasonable to pay less attention; in this practical insight, the weighted least squares (WLS)
analysis provides an efficient and meaningful piece of information to the researchers for
solving the real problem of machine learning programs and also will be flat to influence
on propagating more precise values in machine learning process, specifically instead of
minimizing the family of errors in the above fitted model equation (1.40).
∑ σ1 {Y − αˆ − βˆ X }
n
2
2 i i (1.44)
i
i=1
This criterion will be justified for the estimation of ML assuming ij ~ N µ , σ 2 for ( )
any hypotheses α and β ; the likelihood function of our set of sampled observations
(Y1 , Y2 , Y3 …YN ) is
 1 
1 –
 2σ 2 
[Yi −α + β Xi ]2
L (Y1 , Y2 …Yn ) = exp o + ui (1.45)
∏
n
( 2 π )n/2 i=1
σ2
The likelihood function is maximized when negative exponent is minimized.

Suppose the researcher estimating the standard deviation of the distribution σ i increases
proportionally with X i specifically.
σ i = kX i (1.46)
σi
or =k
Xi
From equation (1.46), the weighted least square analysis WLAS illustrated to minimized
by the following equation (6.23):
∑ k 1x (Y − αˆ − βˆ X )
n
2
2 2 i i (1.47)
i i
i=1
Removing the term generated from the fitted equation (1.47), we modify the equation using
ei
and its SD constant k; thus, the equation becomes
Xi
Yi 1 e
=α + β 0 + β 1 + …β n + i (1.48)
Xi Xi Xi
2
n 2 n
 Yi − αˆ − βˆ X i 
∑ ∑
 Yi 1 ˆ
 X − αˆ X − β  = 
Xi
 (1.49)
i=1
i
i=1  
∑ X1 (Y − αˆ − βˆ X )
n
2
2 i i (1.50)
i
i=1
Finally, equation (1.50) will become WLAS and is modeled in the form of equation (1.47).
∑ k 1x (Y − αˆ − βˆ X )
n
2
2 2 i i (1.51)
i i
i=1
The ordinary least squares (OLS) will tend to be solved in multivariate form with “n”
sampled observations of X and Y. We assumed to be generated from the following steps
used for the formulation of statistical model.
Y11 = α 1 + β11 X 11 + β12 X 12 … + u11
Y21 = α 2 + β 21 X 21 + β 22 X 22 … + u21
Y31 = α 3 + β 31 X 31 + β 32 X 32 … + u31
Yn1 = α n + β n1 X n1 + β n2 X n2 … + un1

 Y11   α 11   u11 
       X 11 
  u12 
 Y12   α 12   β11 β12 β13 X 12 X 13 
   
 Y13  =  α 13  +  β 21 β 22 β 23  ↓x  X 21 X 22 X 23  +  u13 
       X 31   
     β 31 β 32 β 33  
X 32 X 33
 
 Yn11   α n11   un11 
     
(1.52)
Response = Intercepts + Coefficients + Random variables +errors.

From equation (1.47), we model the matrix form for the following equation:
Y = α ′β ( X ) + ui (1.53)
where β = β ′. Without loss of generality, if we take the partial derivatives with respect to
each variable of interest, β 21 = β12
′
∂
= β ′αβ = 2αβ (1.54)
∂β
β ′ = ( X ′X ) X ′Y
−1
β ′ is on multivariate normal with the following equation:
()
E βˆ = β and Cov βˆ = σ 2 ( X ′X ) = σ 2V
−1
() (1.55)
Similarly, the above equation extends to test the different distribution with n (n− k) df,
( ) (σ cvc′) (cβˆ − cβ )
' −1
χ 2 = cβˆ − cβ 2
(1.56)
χ 2 ~ ( c − 1)( r − 1) df
Fisher F ′ = (
1 ˆ
r
′
)(
cβ − cβ σ 2 cvc ′ cβˆ − cβ )( ) (1.57)
F ~ ( r , n − k ) df , where k is the number regressed and r is the number being simultaneously

tested.
From equation (6.29), we assume that ui s are independent errors associated with mean
zero and variance σ 2 .
E ( ui ) = 0 (1.58)
And the covariance matrix of ui’s is an independent error so that ui ~ N 0, σ 2 . ( )

cov ( ui ) = e ( uu′ ) = σ 2 I (1.59)
At this pint of equation (6.35), ui is normally distributed. The MLE function of the above
parameters is as follows:
1 1
( )
L β ,σ 2 = expo − ( y − xβ )′ ( y − xβ ) (1.60)
( 2πσ ) 2 n/2 2σ 2
We can minimize the expression of the equation with respect to the coefficient
( y − xβ )′ ( y − xβ )
= yy ′ − 2 y ′xβ + β ′ x ′xβ
= 0 − 2 y ′xβ + β ′ x ′xβ
Setting this equation equal to zero yields the MLE’s least squares estimates (LSE).
βˆ = ( X ′X ) X ′Y
−1
(1.61)
( )
−1
βˆ = X −1 X ′X −1 ( X ′Y ) = X −1′Y (1.62)
MLE of σ 2 is derived from the following equation:
1
σˆ 2 = ( y − yˆ )′ ( y − yˆ )
n
1
sˆ 2 =
n− k
( y − yˆ )′ ( y − yˆ ) (1.63)
1.10 Susceptible–Infective–Recovered (SIR)
Epidemiological Model of COVID
In any epidemiological study, modeling is a prime factor to define the disease condition
and dynamism of the epidemic. An SIR model is a newer adaptive epidemiological model
that computes the geometric progression and infection rate on theoretical basis derived
from the original data sets, i.e., the number of people infected with a contagious illness in
a closed population over time “t”. The novelty of this model derives from the evidence or
facts relating to the COVID-19 that they involve coupled differential equations relating to
susceptible population S(t), the number of people infected I(t), and the number of people
who have recovered R(t), and these three parameters substitute the death and survival of
cases in fixed period of time. As the first step in the formulation of modeling (modeling
process), we identified the dependent and independent variables from COVID-19 data sets.
The independent variable is the time “t” measured in months or days. From practical point
of view, we consider two related sets of dependent variables (Kermack et al., 1927). The first
set of dependent variables counts the number of people in each of the groups, each as a
function of time “t”. The relation between S(t), I(t), and R(t) is as follows:
S = s ( t ) is the number of susceptible population ( individuals ).
I = I ( t ) is the number of infected individuals .
R = R ( t ) is the number of recovered individuals.
The second set of dependent variables represents the fraction of the total population in each
of the three categories. So, if N is the total population confirmed cases of COVID, the fitted
model in the form of determination of fraction of the population of three parameters is
S (t )
s (t ) = => The susceptible fraction of the population
N
I (t )
i (t ) = => The infected fraction of the population
N
R (t )
r (t ) = => The recovered fraction of the population
N
It nearly seems more natural and original to work with the extrapolation of exact popu-
lation counts, but some of our calculations will be simpler. The two sets of dependent
variables are proportional to each other or no significant relative difference is there in
the population counts, so either data set will produce the same information about the
geometric progression of COVID-19. Under salient assumptions, we have made how s(t),
r(t), and i(t) should vary with time “t”. Rihan et al. (2012) fitted an SIR model incorpo-
rating demographic and epidemiological processes explored from the original data sets
of infectious diseases. We derived four reparameterized quantities of basic demographic
reproductive number (Rd), the fitted model reproduce the ratio of susceptive and infective
class and the relative fecundity of infective class parameters theta, fitted model is more
suited for infectious diseases data sets for extrapolating the exact counts and geometric
progression of the disease and also that are handled by blow up transformation to carry
out a complete and global dynamical analysis. Esteva et al. (2001) and Kermack et al. (1927)
studied the simulation model of a vector-borne disease; the model was formulated based
on the shape and scale parameters with salient assumptions. All newborns are assumed
susceptible, and human vector population is assumed to be constant. The model assumes
a saturation effect in the incidences due to the response of the vector to the change in the
susceptible and infected host pathogens. The stability of the disease-free equilibrium and
existence was derived based on the Thompson iteration method (optimization techniques).
The stability results are given in terms of the basic reproductive numbers. The fitted model
easily describes the salient assumptions of transmission of vector diseases. Esteva et al.
(2001), Kermack et al. (1927), and Cai and Guo (2009) developed dengue SIR epidemic mod-
els with saturation and bilinear incidence. The model formulated a constant recruitment
rate, and the exponential natural death, as well as vector population with asymptotically
constant population, is incorporated into the model fitting. The fitted model exhibited
two equilibria, namely the disease-free equilibrium and the endemic equilibrium. The
stability of these two equilibria is controlled by the threshold reproduction number (R0<1).
The disease-free equilibrium (DFE) is globally asymptotically stable (R0>1), and then the
disease persists and the unique endemic equilibrium point is globally asymptotically
stable. Rihan et al. (2012) fitted a delayed SIR epidemic model in which the susceptible
population is assumed to satisfy the logistic equation and the incidence term is of satu-
rated form with the susceptible population. The present demonstrated model will finally
diagnoses the qualitative behaviors of considering with varied associated biological and
epidemiological parameters. Rodrigues et al. (2016) fitted a simple epidemiological model
that was composed of mutually exclusive compartments of SIR (susceptible, infected, and
recovered). From health concerns to situations related to marketing, informatics, or even
sociology, several are the fields that are using SIR models to describe the disease interven-
tion and economic impact. Hethcote et al. (1995) derived an SIS epidemiological model
considering different attributes, viz. births, natural deaths, disease-related deaths, and a
delay corresponding to the infectious period. The fitted models explore the threshold level
for disease persistence on full-blown population level. The persistence of the disease com-
bined with the disease-related deaths can cause the population size to reduce to zero, to
remain finite, or to grow exponentially with a smaller growth rate constant. Summing the
results describes that the endemic infective fraction is asymptotically stable with varied
parameter values of “θ”. Greenhalgh et al. (1992) demonstrated an SEIR epidemic model
for an infectious disease where the death rate depends on the number of individuals in
the selected population. The model assumed that there is an additional death rate suf-
fered by infected individuals. It was found that there are three steady-state values: (i) one
where the population is extinct; (ii) the population maintains itself at a constant level and
the disease is extinct; and (iii) there is a unique equilibrium with the disease present.
Anderson et al.’s (1982) mathematical models have both limitations and capabilities that
must be recognized. Sometimes, our assumed hypothetical questions cannot be answered
by traditional frequentisitc models. Epidemiological modeling can often be used to com-
pare different diseases in the same population, the same disease in different populations,
or the same disease at different times. A comparison of diseases such as measles, rubella,
mumps, chickenpox, whooping cough, and poliomyelitis was made by Bailey et al. (1975).
Hethcote et al.’s (1995) epidemiological models are useful in comparing the effects of pre-
vention or control of spreading of disease. An SIR model compares the infective, suscep-
tible, and recovered cases simultaneously. The communicable disease models are often the
only practical approach to answering the questions about prevention or control measures
in most effective quantitative real predictions.
1.10.1 Model Formulation
The population considered has a constant size “N”, which is sufficiently large so that the
size of each class is considered as a continuous variable. The model includes real data
driven by the WHO, CDC, vital dynamics than it is assumed death, induced death and
comorbidity parameters was assumed to demonstrate SIR model. Thus, the average num-
ber of S, I, and R per day was considered for model fitting; the daily contact rate γ ′ is fixed
and does not vary seasonally. The type of direct or indirect contacts adequate for trans-
mission depends on COVID-19. The incidence rate, mean transmission cases, and daily
recovered cases were substituted for the reproduction number (R0). Numerical simulations
were reproduced using the Thompson iteration forward method. The following differen-
tial equation triggered the SIR model.
The susceptible–infective–recovered (SIR) epidemiological model of COVID-19 is as
follows:
ds
= − β SI (1.64)
dt
dI
= β SI − γ I (1.65)
dt
dR
= γ I − µR = S + I + R (1.66)
dt
µ > 0 total population infected and death ' d ' β > 0 transmission rate γ . The recovered rate
dN dS + I + R
= = 0 . Therefore, the total population holds constant over time.
dt dt
ds
From Equation (1.64) = µ ( N − S) β SI the total population was considered
dt
dI
= β SI − (γ + µ ) I (1.67)
dt
dR
= γ I − µR (1.68)
dt
S ds
Let s = and u = β I so that the above equation becomes = µ ( 1 − s ) su
N dt
du
= r + µ ( R0 s − I ) u (1.69)
dt
βN
where R0 = is the basic reproduction rate of the disease, s is the fraction of susceptible
γ +u
individuals, and “u” is the measure of the force of the disease; in practical essence, R0 cor-
responds to β , the disease transmission rate, and/or the small recovery rate γ .
R0 = P * C * D (1.70)
P = The transmission probability per exposure.

C = The number of contacts per unit time (mask and preventive measures).
D = The duration of infection per unit time “t”.
The critical vaccination coverage to prevent epidemic is
 1 
Critical vaccination =  1 − = 1 − 0.5 = 0.5
 R0 
The expected number of secondary infections arising from a single infected individual
during the infectious period in a fully susceptible population R0 > 1 disease epidemic R0 = 1;
the endemicity of the disease, e.g., one infected case multiplied with reproduction rate, is
always equal to new infection; 1infected * R0 = new infection
η
dS  S
= −β I ⋅   + σ R
dt  N
η
dE  S
= βI ⋅   − σE
dt  N
dI
= αE − νI
dt
dR
= νI − σ R
dt
β = R0 ⋅ ν (1.8)
The following values were considered for simulation: beta (β): 0.06481, alpha (α): 0.14286,
gamma (γ): 0.01852 and sigma (σ): 0.00274 (Table 1.9).
1.10.2 SIR Model Discussion

The new infection (COVID-19) occurs as a result of contact between infected and suscep-
tible ones. In this fitted model, the rate at which the new infection occurs for some positive
constant, the individual infected cases move from the susceptible class at a defined time
TABLE 1.9
Distribution of Reproduction Number Worldwide
Start Date Jan 1st Week
Basic reproduction number, R0 3–3.5
Latency period, 1/α 0–24 days
Infectious period, 1/γ 60 days
Immunity period, 1/σ 1 year
Mixing parameter, η 2.3
Days 365
period “t”. In an SIR model, there is no other way individuals can enter or leave the sus-
ceptible class, so we demonstrated the model in accordance with the differential equation.
In practical essence, the research by quantitative analysis studied the global behavior of
an SIR model with the stochastic Thompson iteration method (Harville, 1977; Longford,
1987; Mansour et al., 1985). As the deterministic fitted epidemiological model is stochasti-
cally unstable, the global endemic and epidemic equilibria persistently move in the for-
ward direction (R0>1) (Figure 1.14). More number of susceptible cases was added to the
infective class, [E(1,0,0,);E>1;E*>0], which is more than the reference range of reproduc-
tion number (Figure 1.15). Chunyan et al. (2017), Pocock (1983), Johnson (1977), Rao (1965),
Mallet (1986), Fedorov et al. (1993), Lavine (1991), Bryk and Raudenbush (1992), and Chi
et al. (1986) studied the extinction and persistence of a stochastic SIR model and established
a threshold condition called the basic reproduction number under stochastic perturbation
for persistence or extinction of the disease. Guzman et al. (2008) derived a mathematical
model of diseases starting from the same basic premise; the population can be subdivided
into a set of distinct classes dependent upon experience with respect to relevant disease.
The fitted model showed endemic and epidemic equilibria with varied parametric values
(SIR). Milian et al. (2012) and Chou et al. (1989) demonstrated a stochastic epidemic SIR
model of vector-borne diseases with direct mode of transmission and its delay modifica-
tion; the real data deterministic epidemic model was simulated by introducing random per-
turbations around the endemic equilibrium state. As per the model, the results describe a
global stability condition and apparently passes through (malaria) disease condition (R0<1).
Zhao et al. (2013) discussed the dynamism of a SIS stochastic model with association. The
fitted model clearly envisages that the infectiveness decays exponentially to zero regard-
less of the magnitude of reproduction number (R0). When the noise is small, sufficient
conditions for extinction exponentially and persistent in the mean are established. Kim
et al. (2019) and Cox and Hinkley (1974) developed a Coxian distributed SEIR model when
incorporating an empirical incubation period. The results show that the global dynamics
are completely determined by a basic reproduction number. The application of the Coxian
distributed SEIR model has a highest precision. The fitted model is useful for resolving
the realistic intrinsic parts in classical epidemic models since distribution approximately
converges to any kind of distribution as reported by Byun et al. (2019), Melesse and Gumel
(2010), Iwami and Hara (2010), Wang et al. (2014), Hsieh et al. (2010), and Smith et al. (2001).
The infective reproductive rate at time “t” is
Rt = St * R0 (1.71)
where R0 = Per capita rate of infecting others × Duration of infection in a completely

s usceptible population.
Under frequency-dependent transmission,
βN
Rate of infecting others = , where β = Wholly susceptible population
γ
 1 
Duration of infectiousness = 
 Recovery rate 
ds
= r ( S + 1) − γ PS (1.72)
dt
Equation (1.72) shows the transmission of COVID-19

R0 and PS are simulated by the mass contact.
dI
= γ PS − (α + b ) I (1.73)
dt
Equation (1.73) describes how the infectious organisms die out, naturally or preventive
measures with rate “b” or due to infection α
dp
= λ I − ( µ + γ ( s + I )) P described the virus by host (1.74)
dt
Equation (1.74) shows the natural decay of virus and also we estimated infectious organ-
isms transmitted pathogens from equation (1.74)
µ m Cs
where µ = µm = Therateof geomteric expression of exposure , Cs = Mass contact,
K s + Cs
and Ks = Individual contact per population.
1.11 EP Model with Varying Population

The disease-induced death and natural mortality are a simulated reproductive rate, and
it will affect the prime factors of disease severity and the impact on the population. The
following model is developed to know the outbreak of COVID 19 pandemic with varying
population size to know the outbreak and epidemic of the COVID-19 and other infectious
diseases. This formulated model will help healthcare specialists and policy makers in the
implementation of new policies at the early or inception stage (Freedman and Osicka, 2006;
Grimes and Schulz, 2002; Hulley et al., 2001; Mantel and Haenszel, 1959).
N ′ (t ) = (b − d ) µ ′ (1.75)
Exponential dynamic equation (1.44) is utilized for the extrapolation of disease-related

deaths, which can be shown slow at the beginning of the epidemic and follows the expo-
nential trend at time “t”; after preventive measures “d”, the disease dies out and the growth
will decay at time “t”.
 N
r N
N ′ ( t ) = ( b − ar ) K N − dt ( 1 − a ) 
 K
(1.76)
 N
= r1 −  N
 k
The above equation describes the disease-related deaths. How it can drop the popula-
tion size below its carrying capacity or it can drive the population to extinction using the
following equation
dN  N
= KN  1 −  . The logistic model approach was used to determine the exponential
dt  γ 
d dN
growth, if p is small compared to γ ≈ N ; if P > γ , < 0.
dt dt
1.11.1 Reproduction Number Approach to Binomial Distribution (R 0)

The reproduction number will describe the overall epidemic precluded at population
level. The R0 clearly envisages the number of individuals infected from an infected person
at time “t” as per the mathematical equation. We have modeled the expected number of
cases that will be infected in the epidemic area.
R0 = Pi * C j * Dk (1.77)
where Pi = the number of infected cases probability at ith location or provenance;

Cj = the number of cases or individuals infected from mass contact at jth host;
Dk = the number of deaths occurred due to disease or disease-induced deaths.
We assumed binomial distribution (BD) of P(X ≤ x). “X = r” is normally distributed, then
equation (1.46) will become
 n  r n− r
R0 =   p q * C j * Dk (1.78)
 r 
n!
R0 = p r q n− r * C j * Dk
( n − r !) r !
where n is the fixed number of infections obtained from the provenance, P = the probabil-
ity of infection at time “t”, and q = (1 − p).
“μ” is the average population infected = np; SD = npq .
When n → ∞, the probability of infection or death is very small, i.e., P = 0. The BD tends to
Poisson distribution.
Equation (1.47) becomes
 e− µ µ r 
R0 =  * C j * Dk (1.79)
 r ! 
All possible values of “N” have the same chance of probability f ( x ; k ) ( x = r1 , r2 , r3  rn ).
n 2
 r − µi 
r 
µ =  i  , variance σ 2 =
 k ∑i=1

k 

If nβ ( x , r , p ), the R0 number is modeled in the form of the following equation:
 x+r−1  r
 p ( 1 − p ) * C j * Dk − n+1
x
R0 =  (1.80)
 r − 1 
The cumulative distribution function (CDF) of the disease is
 n  x + r − 1  
∑
 
 i=1 
r−1 

p r ( 1 − p ) * C j * Dk − n+1  x = 0 x < 0
x

 1− p 1− p
µ= , variance σ 2 = 2
 p  p
Suppose the population consists of n confirmed cases with ∝ success to reduce the infection
rate. The reproducibility varying with random sample “r” and “k” is
 α  n−α 
 k  r − k 
  
R0 = * C j * Dk − n+1 (1.81)
n
where k = The number of individuals susceptible to infection;
N = The total population of the affected area;
N = The number of samples assessed for the confirmation of the disease (screening);
 γα 
X = The expected number of people who spread the disease E ( x ) =  .
 n 
Suppose we consider N” total population will be infected in different mechanisms at kth

region or provenance, a1,a2,a3…ak with α 1 , α 2 , α 3 α k , then the probability of infection rate
distributed in the form X1, X2, X3…Xn, respectively. The number of elements related from
the a1, a2, a3…ak in a random sample of selected sites for the assessment of geometric growth
of infection is as follows:
 α1   α2   αk 
   … 
 x1   x2   xk 
f ( x1 , x2 , x3 … xk , α 1 , α 2 ,…α k ) = (1.82)
 N 
 n 
 
k N
∑α
i=1
I = N; ∑x = n
I =1
i
The expected number of infections at time t = baseline or days considers R0 = 2. The present
study estimates that the basic reproduction number of the infection (R0) lies between 1.5 and
2.0, and it was approximated to follow binomial distribution and Poisson distribution (PD)
in association with equation (1.46). The results revealed that the incidence rate was <1.0% at
global level as compared to that of general population. The infected rate was found to be ris-
ing at an exponential rate of y = e1.840x. R², which was 89.10%. The prediction value at baseline
was 25,186; the epidemic continued unabated in Hubei region, which was substantially larger
by February 12, 2021. Variants of interest (VOIs) are defined as variants with specific genetic
markers that have been associated with changes that may cause enhanced transmissibility
or virulence, reduction in neutralization by antibodies obtained through natural infection or
vaccination, the ability to evade detection, or a decrease in the effectiveness of therapeutics or
vaccination. So far, since the beginning of the pandemic, the WHO has described eight VOIs,
namely Epsilon (B.1.427 and B.1.429); Zeta (P.2); Eta (B.1.525); Theta (P.3); Iota (B.1.526); Kappa
(B.1.617.1); Lambda (C.37) and Mu (B.1.621). The infection rate was rapidly increasing in other
parts of Chinese cities, and spreading to other countries became more frequent. The model
suggests that travel restriction from and to high prevalence cities of China is unlikely to be
effective in halting the transmissions across China with a 99% effective reduction in travel,
quarantine practical approach will reduce the transmission rate. Our model findings are criti-
cally dependent on the salient assumptions underpinning the model formulation and the tim-
ing and reporting of confirmed cases on February 12, 2021 (CDC, February 12, 2021a database
record), and there is considerable probability that it is associated with the rapid outbreak
at this early stage. With these caveats in mind, our analytical work suggests that the basic
reproductive number of COVID-19 outbreaks is higher compared to other emergent corona-
viruses (Tables 1.10 and 1.11).
R * CFR * P
The deadly index was fitted based on the following formula Di = 0 . Assuming
N
= 10 million at base infection (Figure 1.31), the case fatality rate of COVID-19 was 3% and the
2 * 3 * 364896
probability of susceptible population was 364896; Di = = 0.218. Approximately
10.0 million
21 cases were more prone to the event of death or COVID-induced mortality per 1,000 cases.
As per the CDC (2021a) and WHO report of January 12, 2021, the Chinese health authori-
ties identified more than 40 million infections of COVID-19 as part of the rapid outbreak;
the first case was reported on December 31, 2019. The gene bank database shows the
Wuhan Hu-1 described the sequential database and systematic annotations and metadata
of the SARS-Cov-2 virus. The virus culture was isolated, the first case has contracted the
disease in the Hubei Province of the seafood market. The rapid access to genetic sequence
metadata from public database such as GenBank plays a vital role in developing specific
diagnostic kits for disease outbreaks like these ones. Figure 1.24 shows that the sequential
metadata describe the polygenetic correlation between COVID-19.
TABLE 1.10
Values of the Reproduction Number R0 for Various Infectious Diseases
Disease Transmission R0
Measles Airborne 12–18
Diphtheria Saliva 6–7
Smallpox Airborne droplet 5–7
Polio Fecal–oral route 5–7
Rubella Airborne droplet 5–7
Mumps Airborne droplet 4–7
HIV/AIDS Sexual contact 2–5
Pertussis Airborne droplet 5.5
SARS Airborne droplet 2–5
MERS Airborne droplet <1
Influenza1918 Airborne droplet 2–3
Ebola 2014 Bodily fluid 1.5–2.5
Novel coronavirus 2019 (COVID-19)—the present research Airborne droplet 2–2.5(WHO)
1.5–2(the present study)
TABLE 1.11
Case Fatality Rate and Vaccine Status of Various Diseases
Disease Case Fatality Rate Vaccine
Measles 0.1%–0.20% Yes
Diphtheria 5%–10% Yes
Polio 5%–10% (paralytic polio) Yes
Rubella 3%–6% (developing countries) Yes
Mumps 0.01% Yes
Pertussis 4% Yes
SARSCorona 11% No
MERS 30%–40% No
Influenza1918 <0.10% Yes
Ebola 2014 25%–90% Yes (approved by the
USA and EU)
Novel coronavirus 2019 (COVID-19)—the 2%–3% No
present research
WHO estimates, January 25, 2020; ** this estimate is preliminary and likely to change in the course of the outbreak
dT
Transmission = − β Tv
dt
dI1
Eclipsecell = = β Tv − kI1
dt
dI 2
Infected cell = = kI1 − δ ( I 2 ) I 2
dt
dv
Virus = = PkI1 − Cv
dt
Daily
t Duration
recovered
*
'
S I R Relapsed
Sick patients per day Infection rate daily dead

Died Survival
FIGURE 1.31
Geometric progression and death rate of COVID-19.
1.12 Machine Learning Model for SARS-Cov-19

Machine learning is a newer tool with many methodological interventions. It is delighted
to demonstrate various binary or layered algorithms to learn the salient functions of
input data sets; i.e., the maps are input variables to the target and the output is accu-
rate identification of geographical area (results), which have been generated from the
training data series. For example, we consider Y = f(X), where “y” is the input variable
and the function f(x) is the output (Figure 1.32). The specific model of machine learning
is written in statistical form. The learning is significantly associated with parametric
predictive models. No matter how much data you throw for the building of parametric
model to test the hypothesis, it won’t change its mind about how many parameters will
be needed. Machine learning (ML) has many remarkable merits: (i) Feature selection is
very less important; (ii) It requires fewer assumptions that can drive to superior perfor-
mance; (iii) It may require more training data sets; (iv) The risk of overfitting a model
is often more difficult to explain the medical series data sets. Andrew et al. described
the ML. It is a computer programming model formulated by some pneumonic codes
(programs that people write). In case of machine learning (ML) too many algorithms
(programs) or principles are correlated. Demonstration of ML varies yet is simple in
physical science and more complex in biological, medical, epidemiological sciences to
draw the effective interpretation of multiple data sets or variables (e.g., evidence-based
medicine for the increase in survival age of people who suffer from HIV, cancer, and
Parkinson’s disease in geriatric population). On the basis of a pragmatic approach, the
final decision about the disease at population level, the researcher can clearly under-
stand the hypothesis and complexity (structure) of the entire data sets. In the interest
of model construction we automatically learn the structure and behavior of the vari-
ables. From the following equation, Y= f(x), where “x” is discrimination/prediction
FIGURE 1.32
Machine learning (ML) practical insight.
(regression): f(x) continuous classification: f(x) discrete estimation: f(x) = P(Y = c|x) for
some class c. Looking at the history of machine learning, the first case of neural net-
work was developed way back in 1943 by the neurophysiologist Warren McCulloch
and the mathematician Walter Pitts. They published a research paper on neurons and
how they will work with massive data sets. Further, the researchers decided to formu-
late statistical models on the electrical circuits, and therefore the neural network algo-
rithms is new era for predicting ML era. Way back in 1950s, Alan Turing created the
world famous Turing test. This test was fairly simple as it computed various physical
traits and convinced a human brain for propagating nodes. In 1952 the first computer
program was demonstrated which learn as it ran, designated as a game which played
checkers, created by Arthur Samuel and Frank Rosenblatt who designed the first arti-
ficial neural network (ANN) in 1958, called preceptors; the main goal of this network
was to know the various patterns and shapes at sample level. Another intervention at
early instance of ANNs was modeled in 1959. Bernard Widow and Marcian Hoff created
two models at Stanford University. The first was called ADALINE, and it would detect
binary patterns of various systems. For example, in a stream of bits, it predicted what
the next one would be. The next generation is called MADALINE, and it eliminated
echo on phone lines. Hence, these are useful in the real-world practical applications of
ML problem solving. In 1982, John Hopfield suggested a ML algorithm for creating a
network, which had bidirectional lines. In a similar intervention, he demonstrated how
neurons will actually work in physical and medical science research in the long term.
Further, research was done at global level during 1982, the Japan announced an ANN
model focusing on more advanced neural networks, which incentivized American
funding into the area and thus created more research in the area of physical and inter-
disciplinary sciences. Since the neural networks use backpropagation method for the
validation of time series data and this tool is a very important step to inculcate the
ecosystem of modeling research (introduced in 1986), another invention was done by
Widrow and Hoff in 1962. The Stanford researchers decided to extend the ANN algo-
rithm. ANN will be allowed to have multiple layers inclusion for producing trainer
estimated values, and it is easy to use and has a high level of accuracy. At the start of
twenty-first century, many business lines realized that ANN and ML will increase the
calculation potential. This is why they are researching more heavily in it, in order to
stay ahead of the practical insight of machine learning at global level. In the middle of
twentieth century, a larger number of research groups focused on the machine learning
and its practical approach. For example, Google Brain (2012) demonstrated a deep neu-
ral network invented by Jeff Dean of Google, which focuses on the various patterns for
the detection of textual and non-textual data sets (images and videos). It uses Google’s
resources, which made it incomparable to much smaller neural network operations.
Later, it was used to detect objects in YouTube online videos. Further, AlexNet (2012)
won the image net competition by a large margin in 2012, which led to the use of GPUs
and convolutional neural networks (CNNs) in machine learning. They have also created
ReLU, which is an activation function that greatly improves the efficiency of CNNs. One
more research intervention was demonstrated by DeepFace (2014)—a deep learning
neural network model created by Facebook. They claimed that it can recognize people
with the same precision as a human; DeepMind (2014)—this company was bought by
Google—can play basic video games at the same level as humans. In 2016, it managed
to beat a professional in the gameGo, which is considered to be one the world’s most
difficult board games. OpenAI (2015) is a non-profit organization created by Elon Musk
and others to create safe artificial intelligence (AI) that can benefit humanity.
1.12.1 Machine Learning Model

Machine learning has an algorithm to learn a process or function that maps input vari-
ables to the target output from training data sets; mathematically, we define Yi = Fi(Xi),
where “(Xi = x1,x2,xn)” is the group of independent variates, (Yi = y1,y2,yn) is the group
of dependent variates, and “f” is nothing but a function. The machine learning model
abstains from different learning processes to develop various algorithms of physical and
biological traits; in the state of definition of ML, it is the science of architecture that can
facilitate the statistical, biological and physical decisions about the objects or biological
indictors. The ML high level research concerns how much biological data throwput for
model settings, and it won’t change its mind about how many parameters it needs to
inculcate. The ML requires a fewer number of salient assumptions and can result in the
superior performance of driven algorithms generated from the parametric, patrimonial,
and complex mathematical models. It may require more training data sets in association
with various less risk coverages (overfitting and cost-effective). The rationality of ML is
described in the following (Table 1.12).
• The field has matured both in terms of identity and in terms of methods and tools.
• There is an abundance of data available. We will ensure the abundance of compu-
tation to run methods or models.
• Researcher should ensure the impressive results—increasing acceptance, respect,
and competition-defined machine learning.
• Ensure the Resources + ingredients + tools + desire= population acceptance.
1.13 Models of Machine Learning

The linear model has been considered as the main stem of statistics for the past 30 years
and remains one of our most important tools. Given a vector of inputs X T = X 1 , X 2 ,…X p , ( )
we can predict the output of “Y” from the following equation
TABLE 1.12
Glossary of Machine Learning and Statistics
Machine Learning (ML) Statistics
Network and graphs approach Model approach
Learning (supervised and unsupervised) Fitted or formulated some statistical models to describe random
variables
Generalization of data sets Test set performance
Supervised and unsupervised Regression/classification
Data-driven models, empirically optimized Empirically optimized by model fitting, and unknown parameters
agnostic approach, and exploratory data were obtained based on the scale parameters
analysis insight
Came into existence and flourished in 1990s Been around for centuries, understand how the data is collected
as computer power evolved and the statistical properties, and population distribution learned
Assumes nothing about the data necessary Must determine appropriate parameters to provide predictive power
to handle big or voluminous data
Yˆ j = α i +
β0 + ∑X β + u
i=1
j j (1.83)
Equation (6.1) describes that the term of βj is the intercept, also known as the bias in
machine learning, and often it is convenient to include the constants in ML.
Ŷj = X T βj ′ (1.84)
Figure 1.33 is a practical insight of ML and is a statistics way for model fitting by using
Gauss–Markov method. The nature of error is driven from the measurements taken from
the data points and stochastic condition of random variables (rv) (Fleiss et al., 1981). The
error term is the sum of two components, namely measurement error and stochastic error.
1.13.1 Measurement Error ( u )
There are various reasons demonstrated for our question why “Y” is measured incorrectly.
For example, we are measuring the crop yield in an agricultural experiment. The error
has precluded from sloppy harvesting or inaccurate weights, which are assigned for the
estimation of ML or it may be due to weighing of grains, etc. For example, a study envis-
ages to accomplish the consumption of alcoholin individuals tailored to assessment of
family income at various levels, and the measurement error was extracted from a person
individuated parameter that was collected from tested questionnaires.
1.13.2 Stochastic Error ( u )
The error occurs due to the inherent reproducibility of biological and social phenomena.
Even if there is measurement error that is continuously repeated in experimental area,
the experiment has been using exactly the same amount of fertilizer it would produce
FIGURE 1.33
Flow diagram of SIR epidemiological model.
different yields. These differences are unpredictable and are controlled by stochastic
methods (differences) (Ebrahim and Sullivan, 1995). These stochastic methods will be
reduced by the tighter experimental control, for example by holding constant soil condi-
tions, amount of water, and fertilizer, but complete control is not possible; for example,
the seeds cannot be duplicated. Stochastic error may be regarded as the influence of “Y”
on many omitted random variables of our interest, each with individually yield short of
small error effects. Since the researcher cannot be neutralizing the extraneous influences
by holding the constant factors, as per the practical findings, the best alternative measures
would be taken to minimize the errors (explicitly) associated with fitting of regression
model on X.
From equations (6.1) and (6.2), we shall show to derive the random estimators α i and βj
Eα( )
i = α (1.85)
( )
i = α
2
Var α (1.86)
n
( )
E βj = β (1.87)
( )
Var βj =
σ2
(1.88)
∑ xi 2
where α 2 is the variance of the error ij (the variance of Y). Because of its greater impor-
tance, we shall concentrate on the slope estimator βj rather than αi .
Equation (1.88) may be written as
βj = ∑  xk  k

i
(1.89)
where k = ∑x .i
2
Thus,
βj = ∑ w Y = w Y + w Y + …w Y
i i 1 1 2 2 n n (1.90)
where w1 , w2 , w3 ….wn are the weights assigned for the simulation of supervised machine
x
learning training (mean square errors) and wn = i since each xi is a fixed constant. Hence,
ki
for each wn , we establish the important conclusion about the population or objective of
our interest.
1.13.3 Hidden Gauss–Markov Theorem (HGMT)

The ordinary least squares (OLS) analysis or estimation is the best linear unbiased estima-
tion (BLUE). Under the following salient assumptions, we can prove the hidden Gauss–
Markov theorem (HGMT) by using equation (6.8). Importantly, we consider the analytical
intervention to prove the Gauss–Markov theorem at population level. The postulate of
hidden Gauss–Markov theorem states that all variables are linearly distributed for the
estimation of credibility interval with unknown parameters (θ). The salient postulate was
derived based on the following assumptions. The assumptions were made based on the
state variable (dependent) at a defined time period. For example, the confirmed C OVID-19
cases count is a known variable used to extrapolate unknown factors with quantitative
and qualitative attributes. The attributes were symbolically represented in the hidden
Gauss–Markov assumptions (Dupont, 2008).
• Linearity in parameters—all parameters are linearly related Y = α + β 1X 1 + u.

• Random sampling state variables of “n” observations ( X i , Yi ) ; i = 1, 2, n.
• Sampling variations would be self-explanatory of X i, and all the estimated values
are not the same, X i ≠ ( X i = xI , x2 … xn ).
 u
• The zero conditional mean—the error “u” is expected to be zero, E   = 0 .
 x
• Homogenity of the SARS-Cov-2 data series—errors have shown the same variance
 u
for given values of the explanatory variables, Var   = σ 2 .
 x
NO T E : Homoscedasticity, similar or identical distribution, normally distributed
( )
X ij ~ N µ , σ 2 are independent and from equation (6.8), we estimate βj = CkxnY => βj is
also linear estimators of “Y”.
Let C = ( X ′X ) X ′ + Dkxn and ρ ( D ) = k.

−1
Then, estimate
βj = ( X ′X ) X ′ + D  [ Xβ + u]
−1
= β +  X 1 X −1 X ′ u] + DXβ + Du 
( )
E βj = β + DXβ = [ lk + DX ] β (1.91)
This theorem is a unique tool for the estimation of likelihood of unknown parame-
ters, because it follows normalcy for estimating the even form of weak and large set
of predictions (assumptions were underlined cited above) and hence will not require
assumptions of shape and scale parameters of the known distributions. Each variable of
interest can preclude the error term. In the matter of interpretation of likelihood ratios,
this theorem is more favorable and gives consistent estimated values from machine and
deep learning processes. Let’s consider βj , the least squares estimator of β . Equation (1.9)
was obtained from the nonlinear estimation techniques because they are very easy to
FIGURE 1.34
Predicted values for cases to be infected from coronavirus at global level.
adopt and the concept of estimators can be easily formulated. We restrict ourselves even
further, as shown in Figure 1.34. Within this set of nonlinear estimators, we consider
only the limited class of weights assigned for prediction; the parameter is unbiased.
The Gauss–Markov theorem has an interesting corollary for the estimation of unknown
parameters considering massive data (Hong Zhang et al., 2020). As a special case of
regression model, we might ask what happens if we explain Y, but βj = 0 in that no
independent variable “x” will come into picture.
NO T E : All equations have been derived for the estimation of likelihood by using machine
learning. The embedded equation will emphasize that the GMT is very much restricted
and applies only to estimator that is both linear and unbiased. It follows that there may be
biased or nonlinear estimator that is better (smaller variance) than the least squares esti-
mator (LSE): the confidence intervals and testing hypothesis about “β”.
By using variance and mean, we have determined the Z-values. The condition of nor-
mality of estimator “β” is now in order. First, standardizing “β”, we obtain “Z”.
βˆ − β
Z= (1.92)
σ / 2
∑X 2
i
where “Z” is normally distributed, Z ~ N ( 0,1); i.e., “Z” is normally distributed with mean
and variance. Since the variance of “Y” is generally unknown, it was estimated from
equation (1.92):
n
1
∑(Y − Yˆ )
2
S2 = i i (1.93)
n i=1
where Ŷi is the fitted value of “Y” on the estimated regression line; that is,
Yˆ = αˆ + β X i (1.94)
We have tested the hypothesis on sampled observations from t-test:
βˆ − β
tα = 0.05 = ~ ( n − 2 ) df (1.95)
S2 / ∑ X 2i
Let tα =0.05 denote the “t” value that leaves half of the distribution in the upper tail; that is,
Pr ( −tα =.025 < t value < tα =.025 ) (1.96)
Substituting the above equation, we obtain the following equation:
 
 βˆ − β 
Pr  −tα =.025 < < tα =.025  = .95 (1.97)


S2 / ∑ X 2i 

The inequalities within the bracket may be expressed as
   
 S   S 
Pr  β − tα =.025  < β <  β + tα =.025  = .95

 ∑ Xi 2 


 ∑ Xi 2 

which yields the 95% confidence intervals for slope “β”.
S
β = β ± tα =.025 ~ ( n − 2 ) df
∑ X 2i
From equation (1.97), the family coefficient of the attributes were determined 95% signifi-
cance (CI 95%) (Figures 1.35, 1.36 and 1.37).
Mode of Infection
transmission Virus I1 I2 Death
Clearance production
( )
Eclipse ‘k’
FIGURE 1.35
SIR epidemiological model simulations.
FIGURE 1.36
SIR model simulations with varied parameters.
FIGURE 1.37
Flow diagram of novel coronavirus complete genome from the Wuhan outbreak.
1.14 COVID-19 Mathematical Model Approach to Selective Sample

The COVID-19 pandemic has spread to more than 210 countries. The SARS-CoV-2 has been
controlled by taking preventative measures, viz. avoiding community spread, getting vac-
cinated, wearing masks and frequent hand washing. The Government of India and other
countries implemented a lockdown during the initial stage of the outbreak (March 25,
2020). Many countries followed soon. During the lockdown, measures such as social dis-
tance, self-isolation (stay home and stay safe), quarantine for all suspects, isolation wards,
and treatment for positive cases are being carried out. However, the Government of India,
all the states within the country, and particularly the public are interested in knowing
the reduction in new cases and restoration of normalcy in the country. Further, each state
government wants to prepare/equip itself in terms of doctors, nurses, paramedical staff,
cleaning staff, isolation wards, COVID-designated hospitals, etc., to mitigate the pandemic.
To meet the above objective, each state government should know the expected number
of cases (suspects and positive) periodically. One scientific approach to this problem is
to develop suitable and appropriate mathematical/statistical and epidemiological models
taking into account various pertinent and relevant parameters (Table 1.13 and Figure 1.38).
1.14.1 M odel Formulation
dT
= λ − ( 1 − prt ) KsTVs − ( 1 − prt ) KrTvr + θ − dT (1.98)
dι
dTs
= ( 1 − msr ) ( 1 − prt ) KsTvs + mrs ( 1 − prt ) krTvr − ( µ + d ) Ts (1.99)
dι
dTs
= ( 1 − msr ) ( 1 − prt ) KsTvs + mrs ( 1 − prt ) krTvr − ( µ + d ) Ts + Nsθ (1.100)
dι
dVs
= ( 1 − λ ) β i + ( 1 − prt ) Ksω + mrs ( 1 − prt ) krTvr − ( µ + d ) Ts + (( µ + d ) ε + θ (1.101)
dι
dVr
= ( 1 − λ ) β i + ( 1 − prt ) Ksω + mrs ( 1 − prt ) Tm + Tm′ − ( µ + d ) Ts + ( µ + d )′ ε + θ ( 1 − prt )
dι
Nr ( Ri − θ ) − ν I
dVr  T + T + Tm′ 
= ( λ ) − kTv − dT + 1 − m θ + c − ε I (1.102)
dι  Tmax 
FIGURE 1.38
Flow diagram of novel coronavirus production and transmission mechanisms.
TABLE 1.13
Parameters Included in the Model Construction for the Indian Context
Symbols Description
λi Rate of change of infection at ith geographical location in India
ks Susceptible population immigrated from kth region worldwide
kr The total population sensitive to COVID-19 (risk group)
kvs The total population highly sensitive to COVID-19
d Natural death
d′ Disease-induced death
µ Overall population mean to test the Gaussianity
vs Total population under disease surveillance
vr Total population under treatment Rx
vr Population under quarantine measures
msr Proportion of infected population from COVID-19
msT Proportion of infected population that transmit COVID-19 to native Indians
Ri Self-recovered based on immunity
Prt Relative rate of population infected by COVID-19
Prt′ Relative rate of population to be cured by COVID-19
ϑ Natural decay
NS Reproduction of COVID-19 virus sensitive to risk group and to be infected to the new population
Nr Total population recovered from virus
c Clearance of uninfected cells
Tm The initial time taken for infection
The time taken for the event of death
Tm′
ε Nature balance (time and temperature of the affected area)
ω Pathogenesis of the virus
βi Climatic condition at ith affected epicentric area
θ Incubation period
dTv  T + T + Tm' 
= ( λ ) + kR − dT + 1 − m θ + c − ε I + ω (1.103)
dR  Tmax 
dT *
dι
( )
= kTv − ( µ + d ) 1 − T ** + kTmvTm′ (1.104)
dT *
dv
( )
= N ( µ + d ) ϑθ + ( 1 − ω ) 1 − T ** + kTm − cv + ν I (1.105)
where C = the clearance of uninfected cells, T ′ is the real time taken for the infection in
association with dummy parameter of incubation period, and T ** is the defined intervals
for tracing the suspected population (Table 1.14 and Figure 1.39).
The Government of India has developed mathematical/statistical and epidemiologi-
cal models considering parameters such as suspects (from immigrants of high and low
epidemic countries and contacts from religious congregation), age distribution, relative
TABLE 1.14
Numerical Simulation of the Model
Parameters Values Parameters Values Parameters Values
ks 2,500,000 µ c 0.93
ks ′ 30,000 NS 7,500,000 Tm 6 days

ε 0.25 Nr 1,500,000 10 days
Tm′
ω 0.86 βi 0.015 Ri Log 3.20
θ 24 days d <5%
FIGURE 1.39
Dynamism of novel coronavirus.
rate of infection, environmental conditions, herd immunity including self-recovery, and

preventive measures, viz. social distancing, self-quarantine, screening, testing and treat-
ing time of onset of disease, natural death, and death due to COVID. They predicted
using optimization techniques the number of positive cases at different periods of time
for each state and for the country, taking the number of positive cases recorded in each
state on April 6, 2020, as the base. They are proud to claim that their model and the
technique predicted the number of cases nearer to the number of observed cases with
a margin of less than (10%) error for each state and the country. As an example, they
provide the graph and the table (Table 1.15). One important aspect of their model is to
predict the flattening of the epidemic curve, i.e., the restoration of normalcy for each state
in the country. As per their model, normalcy has restored during the second week of July
2020 (I wave). They also predicted the trend separately for high-, medium-, and low-risk
countries (Figure 1.40).
The prevention strategies and policies were imposed by the Government of India.
Almost all states and union territories implemented lockdown on March 25, 2020. There
will be complete baron the people from stepping outside their homes, besides with
lock down necessary policy law was imposed by the Indian Government for control of
spreading of diseases. The SARS-Cov-2 disease was seeded at initial stage. Figure 1.41
TABLE 1.15
Predicted cases of COVID-19 as of April 6, 2020
States April 6 April 10 April 20
Mizoram 1 1 0
Arunachal Pradesh 1 1 0
Manipur 2 2 1
Jharkhand 3 3 2
Puducherry 5 6 4
Goa 7 8 8
Chhattisgarh 10 12 13
Andaman and Nicobar 10 12 13
Himachal Pradesh 13 16 20
Ladakh 14 17 22
Chandigarh 18 23 31
Uttarakhand 26 34 52
Assam 26 34 52
Bihar 32 42 68
Odisha 39 52 89
Punjab 68 93 183
West Bengal 80 110 225
Haryana 90 125 262
Jammu and Kashmir 106 148 321
Gujarat 128 180 407
Karnataka 151 214 500
Madhya Pradesh 193 277 677
Andhra Pradesh 252 366 937
Rajasthan 266 387 1,001
Uttar Pradesh 278 405 1,056
Kerala 314 460 1,224
Telangana 334 490 1,319
Delhi 503 750 2,156
Tamil Nadu 571 855 2,508
Maharashtra 748 1,131 3,455
Total 4,289 6,256 16,606
depicts that exponential distribution was seen on April 10 and 20, 2020, in Indian States,
especially in Maharashtra, Tamil Nadu, and Delhi, followed by Telangana and Andhra
Pradesh showing highest cases registered and infection rate increasing up to 96.53%.
The Projection of cases on COVID-19 infected was derived from the equation (1.10). The
coronavirus-induced lockdown led to the displacement of millions of migrants and
unemployment, hitting the economy to the rock-bottom level. On the positive front,
the lockdown encouraged India to be self-reliant. Various state governments, centers,
NGOs, corporates, and individuals rose to the occasion to feed the hungry and help
the destitute (Figure 1.41). The rate of infection of COVID-19 from base population is
very low, as per the resulted findings, on an average 1.5–2.0 persons were infected, the
FIGURE 1.40
Virulence of COVID-19 in association with reproduction number (R0).
reproduction number R0 is 1.5–2.0 in high epidemic areas such as Maharashtra, Tamil

Nadu, and Andhra Pradesh, followed by Kerala in the first inception of the disease.
Figures 1.42–1.44 show that the exponential trend model was fitted to know the trend of
infection in different states. COVID-19 exponential trend in India, and the cumulative
number of cases to be infected in the first quarter was 490 (Table 1.16).
COVID-19 Cases
0
100
200
300
400
500
600
700
800
Miz
ora
m
Aru
Rate of infection nac
1
hal
Pra
des
FIGURE 1.41
FIGURE 1.42
FIGURE 1.43
h
1
Ma
0
0.2
0.4
0.6
0.8
1
1.2
nip
ur
2
Jha
Mizoram rkh
and
2
Pud
Arunachal Pradesh uch
e rry
5
Manipur Goa
Jharkhand Chh
5
a
And sga
am rh
Puducherry an
6
and
Nic
oba
Goa Him r
ach
7
al P
rad
Chhattisgarh esh
Andaman and Nicobar Lad

akh
9 10
Himachal Pradesh Cha
COVID-19 Cases
ndig
a rh
Ladakh
Mathematical Modeling of COVID-19
U
14
ara
k han
Chandigarh d
16
Ass
am
Uttarakhand
R² = 0.981
y = e 0.218x
18
Bih
Rate of infection of COVID-19 from base population.

Assam ar
10th April
24
Bihar Od
isha
30
Odisha Pun
jab
Log Scale
Punjab We
st B
eng
al
West Bengal Har
yan
Jam a
Haryana mu
a
49 57 69
nd
K ash
Jammu and Kashmir mir
20th April
Infection rate at Base line infection on April 10 to April 20 in Indian State.
Gujarat Guja
rat
Baseline infection rate on April 10, 2020 and April 20, 2020 in Indian states.
75 104
Karnataka Kar
nat
a ka
Ma
dhy
Madhya Pradesh a Pra
des
h
Andhra Pradesh And
105 128
hra
Pra
des
Rajasthan h
Raja
sth
Uttar Pradesh an
U
159 161
ar P
Kerala rad
esh
174
Cumulative number of cases to be infected by single person in first quarter

Telangana Ker
ala
90.40 91.01
200
Delhi Tela
Expon. ( COVID-19 Cases)

nga
na
295
Tamil Nadu
94.34
Delh
i
411
Maharashtra Tam
il N
445
adu
95.14
Ma
har
a sht
ra
96.53
490
71
40 Susceptible
Population in lakhs
30
20
Quarantine Infected
10
Treated
0
0 2 4 6 8 10 12 14 16
-10
Weeks
FIGURE 1.44
Rate of infection of COVID-19 in base population.
TABLE 1.16
Predicted Deaths and Cases of COVID at the End of April 2020
No. of Cases as Predicted Cases at Predicted
Country of April 7 the End of April Death Deaths
The USA 367,650 2,046,132 10,943 44,200
Spain 140,510 723,304 13,798 57,121
Italy 132,547 678,955 16,523 69,695
Germany 103,375 518,365 1,810 5,896
France 98,010 489,194 8,911 35,198
China 81,740 401,542 3,331 11,734
Iran 60,500 289,296 3,739 13,359
The UK 51,608 243,214 5,373 20,042
Turkey 30,217 135,380 649 1,825
Belgium 22,194 96,460 2,035 6,733
Switzerland 21,855 94,841 784 2,269
The Netherlands 18,803 80,368 1,867 6,107
Canada 16,667 70,366 323 810
Australia 12,399 50,681 243 580
Brazil 12,232 49,776 566 1,558
Portugal 11,730 47,086 311 775
South Korea 10,331 40,854 192 438
Israel 9,006 34,897 59 104
Russia 7,497 28,921 58 102
Sweden 7,206 27,177 477 1,278
India 4,858 17,908 450 593
Total 1,220,935 6,164,718 72,129 280,119
1.15 Recommendations
i. More number of analytical-based study interventions will be required to know
the accurate simulation of reproduction number at the population level; case fatal-
ity rate (CFR) and risk analysis of COVID-19 have been demonstrated with newer
analytical tools before the induction or implementation of health policy at the
global level.
1.20
Exponential Growth Death
1.00
0.80
Growth rate
0.60
0.40
0.22
0.20
0.00
FIGURE 1.45
COVID-19 exponential trend in India.
6.000
5.000
4.000
Rate of infection
3.000
2.000
1.000
0.000
0 20000 40000 60000 80000 100000 120000 140000
-1.000
Average number of population to be infected
5.148 13798
FIGURE 1.46
Susceptible and infected population until Week 14 of COVID-19 pandemic.
ii. The screening of cases would be done based on the mathematical simulation
techniques—artificial intelligence (AI) method. It could be applied at a very early
stage of infection in a suspected or epidemic area and could also strengthen
the quarantine approach through stake holders and policy makers with newer
technologies.
iii. Reduce the infection risk with various prevention strategies (avoid close contact
with inmates or victims, maintain cleanliness, intake thoroughly cooked meat
and meat products, and avoid unprotected contact with wild or farm animals)
(Figures 1.45 and 1.46).
FIGURE 1.47
Trend of SARS-CoV-2 worldwide (2020–2021).
1.16 Study Limitations
The major limitations of the study are the complexity of the model structure and data inter-
pretation due to the uncertainty of the qualitative and quantitative data sets aggravated in
the epidemic area (still the virus rapidly spreads) and also the paucity of literature on novel
coronavirus in the latter part of the study intervention. From the practical and theoretical
points of view, the reproduction number R0 has a determined form of a derived mathemati-
cal model, particularly by using ODE method. The reproduction number (R0) only reflects
the infection rate simply at a threshold level of transmission in an epidemic area, and it
does not yield an average number of secondary infections. This is particularly problematic
if there are intermediate effects between the host, pathogen, and environmental conditions
driven by the triangular form of epidemiological interventions (latent effect) (Figure 1.47).
1.17 Conflict of Interest
There is no conflict of interest between the competent authorities, stake holders, and fund-
ing agencies at national and global levels. The study intervention only focuses on ana-
lytical methods for global health cause and does not try too hard to change or alter the
datasets downloaded from the open-source Web platforms (CDC, WHO, etc.)
References
Anderson R.M., Directly transmitted viral and bacterial infections of man. In: Anderson, R.M. (ed.)
Population Dynamics or infectious Diseases. Theory and Applications. New York: Chapman and
Hall, 1982: 1–37.
Arino J., Portet S., Epidemiological implications of mobility between a large urban centre and smaller
satellite cities. J Math Biol 2015; 71(5): 1243–1265.
Bailey N.T., et al. 1975. The Mathematical Theory or Infectious Diseases, 2nd edn. New York: Harner.
Balcan D., et al. The spatial spread of infectious diseases; The Global Epidemic and Mobility compu-
tational model. J Comput Sci 2010; 1(3): 132–145.
Balcan D., Hu H., Goncalves B., Bajardi P., Poletto C., Ramasco J.J. Seasonal transmission potential
and activity peaks of the new influenza A(H1N1): A Monte Carlo likelihood analysis based on
human mobility. BMC Med 2009; 7: 45.
Basavarajaiah D.M., Narasimha Murthy B., Maheshappa K., Leelavathy B., Mathematical Model
Approach to HIV/AIDS transmission from mother to child. J Sci Technol 2012; 1(9): 45–46.
Bijleveld C., et al. 1998. Longitudinal Data Analysis: Designs, Models, and Methods. Newbury Park: Sage.
Bollen K.A., Curran P.J. 2006. Latent Curve Models. A Structural Equation Perspective. New York: Wiley.
Bryk A.S., Raudenbush S.W. 1992. Hierarchical Linear Models: Applications and Data Analysis Methods.
Newbury Park, CA: Sage Publications.
Buonomo B.C., et al., Stability analysis of Vector bias model of Malaria transmission. Math Bio Sci
2013; 242: 59–67.
Byun J.H., Jung I.H. Modeling to CaptureBystander-killing effect by released payload in target
Positive Tumor Cells. BMC Cancer 2019; 19(1): 194.
Cai L., Guo S., Global dynamics of a dengue epidemic mathematical model. Chaos, Solitons Fractals
2009; 42 (4): 2297–2304.
Castillo Chavez C., et al. Dynamical models of Tuberculosis and their applications. Math Biosci Eng
2004; 1: 361–404.
CDC. 2019. Use authorization. http://www.fda.gov/MedicalDevices/Safety/EmergencySituations/
ucm161496.htm.
CDC February Weekly Review Report. 2021a. https://www.cdc.gov/coronavirus/2019-ncov/
covid-data/covidview/past-reports/01082021.html.
CDC Monthly Report. 2021b. https://www.cdc.gov/mmwr/Novel_Coronavirus_Reports.html.
CDC. 2022a. https://www.cdc.gov/media/releases/2021/s1227-isolation-quarantine-guidance.html.
CDC. 2022b. https://www.cdc.gov/coronavirus/2019-ncov/travelers/.
Chitnis N., et al. Bifurcation analysis of a mathematical model for malaria transmission. SIAMJ Appl
Math 2006; 67: 24–45.
Chitnis, H. Determining important parameters in the spread of malaria through the sensitivity analy-
sis of a mathematical model Bull. Math Biol 2008; 70: 1272–1296.
Chunyan J., et al. The extinction and persistence of a Stochastic SIR model. Adv Differ Equ 2017;
2017: 30.
CNBC 2020. China’s health care system under pressure as corona virus continues to spread. https://
www.cnbc.com/2020/02/26/coronavirus-china-health-care-system-under-pressure-in-wuhan.
html.
Coburn B.J., Wagner B.G., Blower S., Modeling influenza epidemics and pandemics: Insights into the
future of swine flu (H1N1). BMC Med 2009; 7: 30. doi: 10.1186/1741-7015-7-30.
Colizza V., Barrat A., Barthélemy M., Vespignani A. The modeling of global epidemics: Stochastic
dynamics and predictability. Bull Math Biol 2006; 68(8): 1893–1921.
Combat spread of the new coronavirus: https://www.who.int/southeastasia/news/detail/27-01-2020.
Cox D.R., Hinkley D.V. 1974. Theoretical Statistics. London: Chapman & Hall.
Demongeot J., Gaudart J., Mintsa J., Rachdi M. Demography in epidemics modelling. Commun Pure
Appl Anal 2012; 11: 61–82.
Diekmann O.A., et al. On the definition and the Computation of the Basic Reproduction ratio
R0 in the Models for infectious disease in heterogeneous populations. J Math Biol 1990; 28:
365–382.
Dupont W.D. 2008. Statistical Modeling for Biomedical Researchers, 2nd edn. Cambridge: Cambridge
University Press.
Ebrahim G., Sullivan K. 1995. Mother and Child Health Research Methods, 1st edn. London: Book-Aid.
Esteva L., et al. A model for vector transmitted diseases with saturation incidence. J Biol Syst 2001;
9(4): 235–245.
Fedorov V., Hackl P., Mueller W. Estimation and experimental design for second kind regression
models. Informatik, Biometrie und Epidemiologie in Medizin und Biologie 1993; 24: 134–151.
Fleiss J.L. 1981. Statistical Methods for Rates and Proportions, 2nd edn. New York: John Wiley: 38–46.
Freedman M., Osicka T. Reader variability: What we can learn from computer-aided detection exper-
iments. J Am Coll Radiol 2006; 3: 446–455.
Garba S.M., et al., Cross immunity induced backward bifurcation for a model of transmission dynam-
ics of two strains of influenza. Nonlinear Anal RWA 2013; 14: 1384–1403.
Grimes D., Schulz K. Bias and causal association in observational research. Lancet 2002; 359: 248–252.
Gwaltney J.M., et al., Virology and immunology of the common cold. J Rhinol 1985; 23: 265.
Harville D.A. Maximum likelihood approaches to variance component estimation and to related
problems. J Am Stat Assoc 1977; 72: 320–385.
Hethcote H.W., et al., An SIS epidemic model with variable population size and a delay J Math Biol
1995; 34 (2): 177–194.
Hsieh Y.H., Fisman D.N., Wu J. On epidemic modeling in real time: An application to the 2009 Novel
A (H1N1) influenza outbreak in Canada. BMC Res. Notes 2010; 3(1): 283.
Hulley S., Cummings S., Browner W.S., et al. 2001. An Epidemiologic Approach, 2nd edn. Philadelphia,
PA: Lippincott Williams & Wilkins Publishers.
Iwami S., Hara T. Global stability of a generalized epidemic model. J Math Anal Appl 2010; 362(2):
286–300.
Johnson L. Stochastic parameter regression: An annotated bibliography. Int Stat Rev 1977; 45:
257–272.
Keeling M., Rohani P. 2008. Modeling Infectious Diseases in Humans and Animals. Princeton University
Press KCDC, 2020. https://www.cdc.go.kr/board/board.es?mid=a20501000000&bid=0015.
Kermack W.O., et al. Contributions to the mathematical theory epidemics. Proc R Soc 1927; 115:
700–721.
Kim S., Jong H.B., Hyojung I.L. Global stability of an SEIR epidemic model where empirical distri-
bution of incubation period is approximated by Coxian distribution. Adv Differ Equ 2019; 469:
63–66.
Koella J.C. On the use of mathematical models of malaria transmission. Acta Tro 1991; 49: 1–25.
Landry M., et al. Model validation in operations research. Eur J Ope Res 1983; 14 (3): 207–220.
Lavine M. Problems in extrapolation illustrated with space shuttle O-ring data. J Am Stat Assoc 1991;
86 (416): 919–921.
Longford N.T. A fast scoring algorithm for maximum likelihood estimation in unbalanced mixed
models with nested effects. Biometrika 1987; 74: 817–827.
Ma J. Estimating epidemic exponential growth rate and basic reproduction number. J Infect Dis Model
2020; 5: 129–141.
Mallet A. A MLE method for random coefficient regression models. Biometrika 1986; 73: 645–656.
Mansour H., Nordheim E.V., Rutledge J.J. Maximum likelihood estimation of variance components
in repeated measures designs assuming autoregressive errors. Biometrics 1985; 41: 287–294.
Mantel N., Haenszel W. Statistical aspects of the analysis of data from retrospective Studies of dis-
ease. J Nat Cancer Inst 1959; 22: 719–748.
Mateus A.L.P., et al. Effectiveness of travel restrictions in the rapid containment of human influenza:
A systematic review. Bull World Health Organ 2014; 92 (12): 868–880.
Melesse D.Y., Gumel A.B. Global asymptotic properties of an SEIRS model with multiple infectious
stages. J Math Anal Appl 2010; 366(1): 202–217.
Milian J., et al., Stochastic perturbed Vector born disease models with direct transmission. Appl Math
Model 2012; 36: 5214–5228.
Ministry of health, New Zealand. https://www.health.govt.nz/our-work/diseases-and-conditions/
Covid-19-novel-coronavirus.
Morens D.M., Fauci A.S. Infectious diseases: Threats to human health and global stability PLoS Patho
2013; 9 (7): 1003467.
Muthén B., Muthén L. The development of heavy drinking and alcohol-related problems from ages
18 to 37 in a U.S. national sample. J Stud Alcohol 2000; 61: 290–300.
Myint S., Johnstone S., Sanderson G., Simpson H. An evaluation of nested RT-PCR Methods for the
detection of Human Corona Viruses 229E and OC43 in Clinical Specimens. Mol Cell Probes 1994;
8: 357–364.
Notice sent out from Health and Food Safety Planning Division, Quarantine Station Operation
Management Office (in Japanese). https://www.mhlw.go.jp/content/10900000/000582967.
pdf.
Otoo D., Opoku P., Charles S., Kingsley A.P. Deterministic epidemic model for (SVCSy CAsy IR) pneu-
monia dynamics, with vaccination and temporal immunity. J Infect Dis Model 2020; 5: 42–60.
Patel V., Spouge J.L. Estimating the basic reproduction number of a pathogen in a single host when
only a single founder successfully infects. PLoS One 2012; 15 (1): 0227127. doi:10.1371/journal.
pone.0227127.
Pocock S. 1983. Clinical Trials: A practical Approach. Chichester: John Wiley & Sons.
Press statement by Ministry of Health, Labour and Welfare, Japan (in Japanese). https://www.mhlw.
go.jp/stf/houdou/houdou_list_ 202001.html.
Rao C.R. The theory of least squares when parameters are stochastic. Biometrika 1965; 52: 447–458.
Rihan F.A., et al. SIR Model of Swine influenza epidemic in Abu Dhabi; Estimation of vaccination
requirement. J Public Health Front 2012; 1(4): 45–46.
Rodrigues H.S. Application of epidemiological model: New trends. Int J Appl Math Inform 2016; 10:
92–97.
Sanchez C.M., Jimenez G., Laviada M.D., et al. Antigenic homology among corona viruses related to
transmissible gastroenteritis virus. Virology 1990; 174: 410.
Schmidt O.W., Allan I.D., Cooney M.K., et al. Rises in titers of antibody to human Corona Viruses
OC43 and 229E in Seattle families during 1975–1979 Am J Epidemiol 1986; 123: 862.
Siettos C.I., Russo L., Mathematical modeling of infectious disease dynamics. Math Model Infect Dis
2013; 4(4): 295–306.
Smith H.L., Wang L., Li M.Y. Global dynamics of an SEIR epidemic model with vertical transmission.
SIAM J Appl Math 2001; 62(1): 58–69.
Tyrrell D.A., et al. Signs and symptoms in common colds. Epidemiol Infect 1993; 111: 143–156.
van den Driessche J., et al. Reproduction numbers and sub-threshold endemic equilibria for com-
partmental models of disease transmission. Math Biosci 2002; 180: 29–48.
Villela D.A.M. Discrete time forecasting of epidemics. J Infect Dis Model 2020; 5: 189–196.
Wang N., Pang J., Wang J. Stability analysis of a multigroup SEIR epidemic model with general
latency distributions. Abstr Appl Anal 2014; Article ID 740256. doi: 10.1155/2014/740256.
WHO travel advice for international travel and trade in relation to the outbreak of the novel corona
virus 2019-nCoV. https://www.who.int/ith/2020-24-01-outbreak-of-Pneumonia-caused-by-
new-coronavirus/en/.
WHO. 2020Coronavirusdisease (Covid-19) outbreak. https://www.who.int/emergencies/diseases/
novel-coronavirus-2019.
WHO. Eastern Mediterranean Region scales up preparedness for novel coronavirus. http://www.
emro.who.int/media/news/whos-eastern-mediterranean-region-scales-up-preparedness-for-
novel-coronavirus.html.
WHO. https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200212-sitrep-
23-ncov.pdf.
WHO. https://www.who.int/emergencies/diseases/novel-coronavirus-2019.
WHO Report 2022. https://www.who.int/countries/ind.
WHO weekly report, March 2022. 84 edition. Emergency situational updates WHO press : UK ; 2022 ;
http://www.who.int/publications/m/item/weekly-epidemilogical-update-on-covid-19-22
march 2022).
Will Y. Zou, Shenghuo Zhu, Andrew Y. Ng, Kai Yu. Deep Learning of Invariant Features via Simulated
Fixations in Video. In NIPS 2012.
World Health Organisation 2018 World Health Organization (nd). PED (Pandemic & Epidemic
Diseases) Retrieved 10/05/2017. https://www.who.int/emergencies/diseases/novel-corona
virus-2019/situation-reports.
World Health Organization. Therapeutics and COVID-19: living guideline-3 March 2022. Published
online 2022. Accessed March 7, 2022. https://www.who.int/publications/i/item/WHO-2019-
nCoV-therapeutics-2022.2 https://www.cdc.gov/DataStatistics/
Worldometer Section report published on February 18, 2020. https://www.worldometers.info/
coronavirus/
Zaman G., Jung H., Torres D.F.M., et al. Mathematical modeling and control of infectious diseases.
Comput Math Methods Med 2017. doi:10.1155/2017/7149154.
Zhang H., et al. Releasing Wolbachia infected Aedes aegypti to prevent the spread of dengue virus:
A mathematical study. J Infect Dis Model 2020; 5: 142–160.
Zhao Y.N., Jiang D.Q., et al. The extinction and persistence of the stochastic SIS epidemic Model with
vaccination Phys Appl 2013; 392: 4916–4927.
2
Time Series Stochastic Projection Models
for the Estimation of COVID Trend
2.1 I ntroduction
In realistic approach, SARS-Cov-19 pandemic has a tremendous impact on human liveli-
hood and is changing overall health domains. Transitional changes were observed during
the intervention of pandemic; we live to drive extraordinary acts of human compassion
(Coronavirus update live Worldometer, 2020). At present, health policy is in an alarming
state; for continuous development of health domains and overall quality of life, we need to
preserve human values and ethics. The disruption and perseverance is more evident now
than ever among the frontline healthcare workers who continue to respond tirelessly for
the control of pandemic. Researchers are required to determine the actual facts and figures
of pandemic crisis accurately, and they need to formulate a plan for the eradication of this
deadly disease. In this scenario, projection models attempt to forecast the critical juris-
diction of public health policy of country as well as at the global level (Chadsuthi, 2012).
Many research works have been undertaken by various research organizations for accu-
rate estimation of progression of COVID pandemic (Coronavirus update live Worldometer,
2020). Projection models allow us to estimate the target that supersedes the population
and enable us to develop public health policy interventions worldwide. The projection
models can deliberately contribute important practical insights into public health deci-
sions and national policy interventions, also allowing us to examine the health issues and
to eradicate present pandemic scenarios (Abdelghafour et al., 2020). The predictive mod-
els are more suitable to forecast future observations by accurate simulation on different
data points based on the past and present situations. Here, we have modeled the COVID
pandemic on various attributes (based on different measures) that were considered for
the control of pandemic outbreak situations worldwide Azizi et al., 2020). By using vari-
ous formulated modeling techniques (presented in this chapter), we will try to find the
propagation rule on outbreak of this deadly disease and control measures analytically
and will accurately predict pandemic situations at national and global levels. With global
data, the projection model gives the best results for the simulation of projection of various
data points with different time intervals. In this section, we compare other models fitted
earlier by considering all variables of SARS-Cov-19 (Wang et al., 2020). Based on theoretical
postulate, stochastic time series analysis (smoothing bootstrap techniques) has formulated
using random process, we predict all variables of next precedent time that the total posi-
tive cases recorded. This chapter describes various projection models on stochastic basis.
Our fitted models will provide accurate and better forecasted values of COVID clinical
and diagnostic characteristics (Wang et al., 2020).
DOI: 10.1201/9781003204794-2 79
2.2 Time Series Stochastic Models

2.2.1 E xponential Smoothing by Bootstrap Techniques
Exponential smoothing is a more advanced method applied in many areas, including
agriculture, engineering, and physical science (Chatfield and Yar, 1988; Dominici et al.,
2003; De et al., 2016). In the real situation of COVID-19 pandemic, exponential smooth-
ing is a very advanced technique for the extrapolation of accurate geometric progression
and normalcy restoration level at national and global levels. All data points are merged
in bootstrap techniques, and the models are examined based on the Thompson iteration
method. All intervention models are demonstrated using real data of COVID (collected
from the Scintillant Surveillance Center Open Platform; global data). An exponential
smoothing is one of the most powerful and trusted techniques in predictive analytics,
especially in demand forecasting. It is important to understand the basic premise of the
techniques to be able to effectively use it when available in various forecasting software
(Costagliola et al., 1994).
Ft = Ft−1 + α ( At−1 − Ft−1 ) (2.1)
Ft = New forecast of COVID cases;

Ft−1 = Previous forecast of COVID cases ;
α = Smoothing constant for extrapolation of bootstrap;
At−1 = Previous COVID cases recorded at different time intervals.
Ft = α ( At−1 ) + ( 1 − α ) Ft−1 + Tt−1 (2.2)
Tt = β ( Ft−1 − Tt−1 ) + ( 1 − β ) Tt−1
Ft = Exponential smoothing forecast of the data points at time “t”;

At = Actual positive cases detected in the period “t”;
α = Smoothing constant for the average ( 0 ≤ α ≤ 1);
β = Smoothing constant for the trend ( 0 ≤ β ≤ 1).
Using real data sets of COVID, one way we have is to modify the influence of the past on
the mean forecast at particular data points; on the outset how many preceding observa-
tions will be included in a mean (Healy, 1983). The term MA is used to describe this proce-
dure because each new observation becomes available; a new average can be computed by
dropping the oldest observation and including preceding values or data points (Jackson
et al., 2007).
2.2.2 Holt–Winters (HW) Triple Exponential Smoothing Method

Holt (1957) and Winters (1960) invented an advanced method to forecast and capture sea-
sonality. The HW method comprises an equation of three smoothing constants α , β , and γ
, where m is used for frequency of the seasonality, i.e., the number of seasons in a selected
data sets m=6m=6. There are two variations in this method that differ in the nature of the
Time Series Models for Estimating COVID Trend 81
seasonal component. The additive method is preferred when the seasonal variations are
roughly constant throughout the data series, while the multiplicative method is preferred
when the seasonal variations are changing proportional to the level of COVID data series.
In case of additive method, the seasonal component is expressed in absolute terms in case
of observed cases of COVID data series, and in the level equation, the series is seasonally
adjusted by subtracting the seasonal component. Within each month of COVID record cases,
the seasonal component will add up to approximately zero. With multiplicative decompo-
sition, the seasonal component is expressed in relative terms and the series is seasonally
adjusted by dividing through component. The seasonal component will sum up to approxi-
mately “m”.
Ft
St = α + ( 1 − α ) ( St−1 + bt−1 ) Overall smoothening (2.3)
Ct − L
bt = γ ( st − St−1 ) + ( 1 − γ ) bt − 1 Trend smoothening (2.4)
F
It = β  t  + ( 1 − γ ) It − 1 Seasonal smoothing (2.5)
 St 
Ft+ m = ( St + mbt ) It− L+ m Forecast (2.6)
α = 0.59, β = 0.63 γ =0
2.3 A RIMA Forecasting Model Approach to

COVID Progression Estimation
ARIMA model is an advanced time series model that provides another approach to time
series forecasting (Sahai et al., 2020). The exponential smoothing and ARIMA models are
the two most widely used approaches for time series forecasting of COVID progression
at national and global levels. These models will necessarily provide a benefited compli-
mentary approach during the pandemic stage (Shmueli and Burkom, 2010; Shewhart et al.,
1931). While exponential smoothing models are based on a description of the trend and
seasonality in the data, ARIMA models aim to extrapolate the autocorrelation function in
association with bootstrap constants (mean value).
The following steps were used for ARIMA model: State and define the ARIMA equation
so that Yt is on the left-hand side and all other terms are on the right. Rewrite the equation
by replacing “t” with (T + h).
On the right-hand side of the equation, replace future observations with their fore-
casts, future errors components with zero, and past errors with the corresponding
residuals.
Step 1: Autoregressive model is formulated based on the random error and predictors
of COVID-19.
Yt = C + Φ1Yt−1 + Φ 2Yt− 2 …Φ pYt− p + t (2.7)

where t = the errors associated with time “t”, Yt = the predictor variable of COVID,
P = the autoregressive model of the order “p”, and C = a constant.
The ARIMA model is remarkable and flexible at handling wide range of different time
series patterns (Alsundani et al., 2017). The variance of the error term t will only
change the scale of the data series, not the patterns.
When Φ1 = 0, Yt is equivalent to noise data.
When Φ1 = 1 and C = 0 Yt is equivalent t o a random walk.
When Φ1 = 1 and C ≠ 0 Yt is equivalent to a random walk with drift.
When Φ1 < 1 Yt is equivalent to oscillation (surrounded) around the mean value; AR(1) lies
−1 < ∅1 < 1; AR(2) lies −1 < ∅ 2 < 1; when p ≥ 3, the restriction is much more ∅1 + ∅ 2 < 1,
∅1 − ∅ 2 < 1; “R” takes care of these restrictions when estimating a model.
Step 2: Beginning with t = 1, these steps are n times repeated for t = 2, 3,…, until all
forecasts have been calculated. We will illustrate it using the ARIMA (0,0,0), (0,0,1),
(1,1,1) models demonstrated by the following equation.
( )
Yt = C + ( 1 − Φ 0 ) t0S0 + ( Φ1 − 1) t1S1 + ( Φ 2 − 2 ) t2S2 … Φ p − 1 Yt− s + t (2.8)
where t0S0 is the initial outbreak multiplied with seasonal effect driven by decomposi-
tion method.
Applying the backshift operation will give
yt − ( 1 + ∅1 ) t0S0 + ( ∅1 − ∅ 2 ) t1S1 + ( ∅ 2 − ∅ 3 ) t2S2 + Φ 4 yt− s = t + θît− s (2.9)
We move all terms other than yt to the right-hand side.

yt = ( 1 + ∅1 ) yt−1 − ( ∅1 − ∅ 2 ) yt− 2 − ( ∅ 2 − ∅ 3 ) yt− 3 + Φ 4 yt− 4 = t + θît− s+1 (2.10)
where θî is the random walk stochastic estimation using bootstrap techniques
(Figures 2.1–2.3).
FIGURE 2.1
Exponential smoothening of COVID-19 Indian data.
FIGURE 2.2
Extrapolation of exponential smoothing.
The equation (2.10) used for extrapolation of forecast in correlation with the ARIMA model
for a time series Y [ t ] = ( for t = 1, 2,T ). The planner may specify a cutoff period of “K”,
which simplifies the ARIMA model. It was estimated based on Y [ t ] = ( for t = 1, 2,T − K )
such that the extrapolation forecast F (T ) = for T − K + 1…T is computed and compared
with the actual values that were dropped; different various extrapolation forecasting tech-
niques were done as compared and computed MPE, RMSE, MAPE, etc. In addition, the
following P values were computed: P(F[t] > Y[t − 1]), P(F[t] > Y[t − s]), and P(F [t] > Y [T − K]).
As per the literature (Sahai et al., 2020), COVID is enormously spreading worldwide
and it is infecting millions of people. This debilitating virus is highly contagious, and the
infection is transmitted through respiratory droplets of infected persons. The spread of
COVID can be classified into three stages, viz. (i) local outbreak, (ii) community transmis-
sion, and (iii) large-scale transmission—at this stage, the virus spreads rapidly to other
regions of a country due to the uncontrolled large-scale mobility of people exacerbated by
very high virulence of the virus, making our interventions futile and unable to control the
fast spreading. In this paradigm, healthcare researchers and policy makers should make
an attempt to control the existing pandemic by implementing various prevention strate-
gies; also, they should try to extrapolate different control measures at population level.
After the intervention of pandemic stage, many researchers have addressed the issues and
challenges at right time. Valid policy decisions were implemented by the concerned health
authorities at national and global levels (WHO, 2020). An intervention of new policy is
necessary to control endemism. Analytical research findings are very important to draw
the valid inference about the affected population. Suitable statistical modeling or tools
will support us in gathering information and performing complex analysis of COVID
data sets (collected from affected areas) (Stroup et al., 1993; Stern and Lightfoot, 1999;
Serfling, 1963). The statistical modeling would alienate to represent the entire perspective
of the disease condition and transmission status and also furnish valid research findings
to the researchers and policy makers for the implementation of innovative measures to
control this pandemic. The first step of the model is to test the unit root value of COVID
time series data (which are collected from the monitoring of rate of occurrence of specific
diseases/conditions through a voluntary network of doctors Sentillant surveillance). The
entire series was examined on a visual basis by using a separate software package, and a
Plot the data, identify

unusual observations,
understand patterns
Select Use
If necessary, use a Box–
model automated
Cox transformation to
order algorithm
stabilize the variance
If necessary, difference
the data until they appear Use auto ARIMA to
stationary. Use unit find the best
root tests if you are ARIMA model for
unsure time series data
Check the residual from

Plot the ACF/PACF of your chosen model by
differenced data and try plotting the ACF of the
to determine possible residuals
candidate models
Try your chosen model

and use the AIC to search
for a better model Calculate forecasts
Yes
No
Do the residuals look like

white noise
FIGURE 2.3
Steps or process of ARIMA model formulation.
data plot was created. As per the data review, COVID-19 positive cases show an exponen-
tial rise in all states of India (except few states) (Unkel et al., 2011; Wang, Li et al., 2020).
Data series was measured in the first order, second order and so on. We should make
convenient adjustments in the data without any loss of information for data compilation
and model demonstration purposes. The residual of the ARIMA (1,1,0) and (0,0,1) was
simulated and plotted in graphs and diagrams (Figures 2.4 and 2.5). The ARIMA model
was then used to forecast the quintile of COVID outbreak estimation of first wave (disease
incepted from January to October 2020). The forecasted values for each state (provenance)
are presented in Table 2.1. Table 2.2 shows the ARIMA (1,1,0) forecasted values of top six
Indian states (high incidence). The forecasted figures show that PE for Delhi was 0.80;
RMSE 0.00; Scaled 1.87 lakhs; and MASE 1.87 lakhs. The first case of COVID was reported
in Kerala. It had a significantly high RMSE value (524,926) with Scaled 2.27 lakhs and
FIGURE 2.4
ARIMA (1,1,0).
FIGURE 2.5
ARIMA (0,1,1).
MASE 2.07 lakhs. The highest number of cases was found in Maharashtra; approximately
991,877 cases were recorded (PE 0.92; Scaled 7.26 lakhs; MASE 3.51 lakhs). This state was
followed by Karnataka with 714,036 cases, Scaled 3.43 lakhs, and MASE 2.77 lakhs. In
case of Andhra Pradesh, the value of PE was 0.96; it recorded 671,199 cases with Scaled
3.31 lakhs and MASE 2.60 lakhs. The distribution of ACF is represented in Figure 2.6.
TABLE 2.1
ARIMA Forecasting Output
Univariate ARIMA Extrapolation Forecast
P(F[t] > P(F[t] > P(F[t] >
State Y[t] F[t] 95% LB 95% UB P-Value Y[t−1]) Y[t−s]) Y[30])
UP 505,054 - - - - - - -
Delhi 556,397 - - - - - - -
Kerala 593,924 663,857 21,827 −23,363 0.58 0.38 0.38 0.38
TN 639,664 560,732 8,671 −8,948 0.61 0.55 0.55 0.49
AP 791,552 455,554 4,325 −4,409 0.92 0.78 0.78 0.67
Karnataka 872,288 331,215 2,545 −2,584 1.00 1.00 1.00 0.91
Maharashtra 894,004 245,237 1,642 −1,664 1.00 1.00 1.00 0.99
2E+06 182,329 1,134 −1,148 1.00 1.00 1.00 1.00
TABLE 2.2
ARIMA (1,1,0) Model Output
Univariate ARIMA Extrapolation Forecast Performance
State % SE PE MAPE SMAPE Sq. E RMSE Scaled MASE
Delhi −0.66 0.80 0.80 1.32 2.23649E+11 0.00 1.87 1.87
Kerala −0.69 0.89 0.85 1.47 3.27446E+11 524,926 2.27 2.07
TN −0.69 0.94 0.88 1.57 5.53696E+11 606,847 2.95 2.36
AP −0.68 0.96 0.90 1.64 6.97244E+11 671,199 3.31 2.60
Karnataka −0.68 0.97 0.91 1.68 7.47203E+11 714,036 3.43 2.77
Maharashtra −0.68 0.99 0.92 1.73 3.35368E+12 991,877 7.26 3.51
FIGURE 2.6
Distribution of ACF.
FIGURE 2.7
Residual density plot with respect to residual points.
Figure 2.7 shows the residual density plot with respect to residual points of all states.
The graph clearly depicts that approximately 2.50 lakhs of people are likely to be exposed
to COVID infection per week. This high density was augmented in the first and second
waves of COVID-19 pandemic. Using projection points of the model, normalcy will be
restored gradually starting from the end of calendar year 2020 until the first quarter of
2021 (January, February, and March 2021). In other words, our forecasted values indi-
cated that the situation had worsened and the steepest ascent was observed during June
to October 2020 (Table 2.3). Further, the ARIMA average decomposition method was
employed to forecast the COVID cases to know the seasonal, cyclic, and trend variations
of all states. The resultant forecasted figures are presented in Table 2.4. The results on
each state of observed cases were simulated with a lag period of 3–4 weeks, and we esti-
mated the seasonal, trend, and random effects of the model. The results show the seasonal
variation as follows: Kerala (40,336 k), Tamil Nadu (30,648 k), Andhra Pradesh (22,090 k),
Karnataka (15,874 k), Maharashtra (11,537 k), and Delhi (7,805k). Himachal Pradesh (1,817
k), Uttarakhand (22,095 k), Jharkhand (35,958 k), and Assam (6,670 k) show random effects
with marginal differences; <20,000 k positive cases seem to be infected; time-varying
changes in MA decomposition method were employed. The forecasted values are plot-
ted in Figures 2.8–2.10. ARIMA is better reproducibility measures of the forecast effi-
ciency to replicate MAPE which converts the absolute deviation as percentage of actual
numbers and robustness of the model was diagnosed by the coefficient of determination
R 2(%) = 0.93 and Akaike information criterion (136.22). The ARIMA model for COVID
forecasting is more robust, and each individual series of data sets will produce accurate
TABLE 2.3
ARIMA Backward Selection
ARIMA Parameter Estimation and Backward Selection
Iteration ma1 sar1 sma1
Estimates (1) −0.4707 1 −0.4707
P-value 0.2208 0 0.2208
Estimates (2) 0 0.957 −0.7181
P-value NA 0 0.0028
Estimates (3) NA NA NA
P-value NA NA NA
P-value NA NA NA
P-value NA NA NA
TABLE 2.4
ARIMA Average Model Decomposition Method
Classical Decomposition by Moving Averages
States Observations Fit Trend Seasonal Random
Dadra and Nagar Haveli and Daman and Diu 3,346 NA NA −22,445.8 NA
Mizoram 3,968 NA NA −32,895.2 NA
Andaman and Nicobar Islands 4,773 NA NA −43,182 NA
Sikkim 5,203 NA NA −41,421.6 NA
Ladakh 8,896 NA NA 16,313.4 NA
Nagaland 11,418 NA NA 7,804.78 NA
Meghalaya 12,314 57,007 16,670 40,337 −44,693
Arunachal Pradesh 14,415 50,950 20,302 30,648 −36,535
Chandigarh 18,113 47,331 25,241 22,090 −29,218
Manipur 26,225 48,574 32,699 15,875 −22,349
Tripura 32,925 52,983 41,446 11,537 −20,058
Puducherry 37,270 47,206 51,867 −4,661 −9,936
Himachal Pradesh 45,697 43,880 66,326 −22,446 1,817
Goa 48,776 50,144 83,040 −32,895 −1,368
Uttarakhand 78,509 56,414 99,596 −43,182 22,095
Jharkhand 110,457 74,499 115,920 −41,422 35,958
Jammu and Kashmir 113,568 148,887 132,573 16,313 −35,319
Punjab 156,839 157,617 149,812 7,805 −778
Assam 213,925 207,255 166,919 40,337 6,670
Madhya Pradesh 215,957 215,413 184,764 30,648 −1,488
Gujarat 220,168 224,762 202,671 22,090 −8,805
Bihar 238,648 235,842 219,968 15,875 −15,674
Haryana 245,288 256,613 245,076 11,537 −17,965
Chhattisgarh 248,232 273,375 278,036 −4,661 −28,087
Telangana 274,540 288,072 310,517 −22,446 −39,840
(Continued)
TABLE 2.4 (Continued)

ARIMA Average Model Decomposition Method
Classical Decomposition by Moving Averages
States Observations Fit Trend Seasonal Random
Rajasthan 282,512 311,195 344,090 −32,895 −36,655
Odisha 321,564 342,630 385,812 −43,182 −60,118
West Bengal 505,054 395,545 436,967 −41,422 −73,981
Uttar Pradesh 556,397 507,758 491,445 16,313 −2,704
Delhi 593,924 593,642 585,837 7,805 −37,245
Kerala 639,664 NA NA 40,336.6 NA
Tamil Nadu 791,552 NA NA 30,648.4 NA
Andhra Pradesh 872,288 NA NA 22,090.2 NA
Karnataka 894,004 NA NA 15,874.7 NA
Maharashtra 1,855,341 NA NA 11,537.2 NA
FIGURE 2.8
Moving average (MA) fitted decomposition of additive time series.
results and generate accurate projected values of COVID cases. The model absolute devia-
tion of MAPE is very less compared to SE (%); all values are negative. In advanced stage
of infection, the model estimation/simulation would be readjusted by a scale value for
projection of various data points at population level. Researchers should apply Box–Cox
transformation to stabilize the variance and lag period that will be readjusted based on
the threshold level of infection, and we can run the model for backward movement pro-
jections (selection). It will provide efficient results when we are readjusting the threshold
level of pandemic. We have demonstrated an advanced ARIMA considering threshold
level by applying a simple iteration method, and it was employed for smoothing of data
series (Table 2.2). As per the findings, there is no effect of prior movement or disease pro-
gression in the forthcoming quarters of 2022. It could not affect the residual factors over
a period of time. All estimates showed 0 and values < 1 with scale parameter P = 0.22.
Approximately 22% shortfall in variations will be observed in the forthcoming waves of
COVID (Table 2.2 and Figures 2.11 and 2.12).
FIGURE 2.9
Seasonal variation of COVID data points.
FIGURE 2.10
Trend variations of COVID data points.
FIGURE 2.11
Variation of model output (1,1,0).
FIGURE 2.12
PAF distribution of various lag points.
2.4 Model Discussion

In the Indian scenario, the control of pandemic continues successfully until September
2020 (first wave of infection). Many prevention measures and strategies were under-
taken to control the spread. Draconian measures such as lockdown, compulsory wearing
of masks, avoidance of ritual functions, and avoidance of crowded population in public
places will be more helpful in restoring normalcy. After the lockdown was lifted by the
Indian Government authority, migrant laborers from several cities including metropolitan
cities in the high endemic states started to move out (e.g., Karnataka, Mumbai, Delhi, Tamil
Nadu, and Kerala), which resulted in a drastic explosion of the pandemic, and the toll went
past >25 lakhs in a couple of months. Virus virulence drastically increased, and the pan-
demic will start from the end of April to June 2020. From the model output, India break
into the top ten affected worsen countries (the USA, Brazil, Spain, etc.). This model output
is expected to provide better policy interventions for the burgeoning demand for health-
care facilities. However, overwhelmingly, the model output is very commendable and
justifiable for predicting the forecasted figures of infectious disease, and extensively, we
extrapolate the results without any overlapping data series and formulation (Kotwal et al.,
2020). The present formulated had certain limitations: it suffers propagating the projected
values on the basis of frequentisitc approach, because fudicial limits (confidence limits)
are fixed with desired level of significance with time-varying probability distribution. The
model was found to have widespread and successful analytical applications in the estima-
tion of various infectious disease outbreaks, formulated will be express on the autore-
gressive nature of the time series data points, which can predict forward and backward
bifurcation of time series data with desired level of significance and different lag periods
of infection (Kotwal et al., 2020; Wang, Li et al., 2020). The nature of the model forecasted
the COVID progression up to March 2021 (first quarter of the year). The curve would be
expected to flatten by the end of March 2021 or April 2021. The adjusted hazard risk is <1%
(Basavarajaiah and Narasimha Murthy, 2020). In the Indian scenario, the adjusted hazard
risk will move in the downward direction because the population has herd immunity.
2.5 Conclusions
The time series ARIMA model’s output showed that the COVID-19 pandemic would stablize
by the end of March 2022. Our predicted model can be more useful and robust for predicting
time series data sets of COVID-19 without any overlapping assumptions that are correlated
by the researchers. The forecasted figures would be used by the concerned healthcare orga-
nizations, clinicians, and planners of the health policy makers for the implementation of
health policy, for better management of the affected population and also ramp up their
healthcare preparedness for the pandemic.
2.6 R andom Walk Markov Chain Stochastic Transient (RMCST) Model

A typical random walk involves some value that randomly wavers up and down over
time; commonly, we have analyzed what is the probability that the wavering value reaches
some end value and the time taken for that to happen; e.g., a drunkard will reach his home
or end up in the river (Azizi et al., 2020). A Markov model is a statistical method for ran-
domly changing systems where it is assumed that the future states do not depend on the
past states. These methods show all possible stages of COVID-19 pandemic, transmission,
rate of infection, and propagated transitional probabilities between and within the data
series of COVID. This method is generally used to recognize various patterns. It will make
prediction and allow us to learn the extracted sequential patterns of unobservable com-
ponents of data series. In case of a Markov model, there are four types of models that are
used, viz. (i) Markov chain—used by systems that are autonomous and have fully observ-
able states, (ii) hidden Markov model—used by systems that are autonomous where the
state is particularly observable, (iii) Markov decision process—used by controlled systems
with a fully observable state, and (iv) partially observable Markov decision process—used
by controlled systems where the state is partially observable.
Definition of Markov chain model: A Markov chain is a discrete-time stochastic process
( X n , n ≥ 0) such that each random X n takes a value in a discrete set “S” [S = N, typically]
and   X n+1 = j / X n = i, X n−1 = in−1 … X 0 = i0  =  ( X n+1 = j X n = i ).
That is, as the time goes by, the process loses the memory of the past.
If, moreover,   X n+1 = j / X n = i  = Pij is independent of “n”, then “x” is said to be time
( )
homogeneous. The Markov chain S is a finite set, S = {0, 1, 2 N }; typically, P = Pij ij∈s is
called transition matrix of the chain and always provides the time homogeneous Markov
chain by transition acyclic graphs.
Ru = Pr(Covid move to end / started at ' u ')
Ru = 0.5 Ru−T 1 + 0.5 Ru + T 1 = 1 (2.11)
u
Ru =
w
 u
Ru = Pr ( Covid move to end / it started at ' u ') =  
 w
 w − u
Ru = Pr ( Covid not move to end /it started at ' u ') = 
 w 
Du = Expected number of waves or fluxes to reach normalcy, from starting position “u”
Du = 1 + 0.5Du1 + 0.5Du+1 ; D0 = 0 Dw = 0
Du = u ( w − u + T 1 − k ) (2.12)
In probability theory, a Markov stochastic model is used to extrapolate a randomly chang-

ing system, where it is assumed that future state depends only on the present state and not
on sequences of the vents that preceded generally and these assumptions enable reasoning
and computation with the model that would otherwise be intractable. Following assump-
tions were made for the formulation of the stochastic model.
A varied set of states, fixed transition probabilities, and the possibility of getting from
any states to another through a series of transitions.
A Markov process converges to a unique distribution over states. This means that what
happens in the long run won’t depend on where the process started or on what happens
along the way.
What happens in the long run will be completely determined by the transition probabil-
ity and the likelihoods of moving between the various states.
Property: Let ut+1 be the defined random state of the COVID-19 transmission process at
time t + 1, which depends only on the state of system at time “t”.
Pr ( ut+1 … ut+1 … ut= u ut )
Pr ( ut+1 … ut+1 / ut= ut )
Pr ( ut+1 … = b ( ut= a )) = pab
The transition matrix is as follows:
 p11 p12 p1s   u11 u12 u1s 

   
p =  p21 p22 p2 s  Or p =  u21 u22 u2 s 
   u31 u32 u3 s 
 p31 p32 p3 s 
  
For each I= ∑u
i=1
ij =1 (2.13)
Hence, all entries in the transition probability matrix are non-negative and the sum of entries
in each row is equal to 1. Suppose different waves of reproduction number (R0) was deter-
mined from selected sites. The reproduction number will be multiplied with the transition
probability with rows; we will get accurate prediction probability of progression of COVID.
R0 = [R 01 , R02 , R03]

 p11 p12 p1s 

 
R0 = [ R01 , R02 , R03 ]  p21 p22 p2 s  ↓
 
 p31 p32 p3 s 

Reproduction number [Transition matrixes] * ( Time period )
 p11 p12 p1s   T11 T12 T1s 

   
R0 = [ R01 , R02 , R03 ]  p21 p22 p2 s  ×  T21 T22 T2 s  (2.14)
 
 p31 p32 p3 s   T31 T32 T3 s 


From equation (2.6), we will get geometric progression of COVID spread with varied time
transition probabilities.
TABLE 2.5
Augmentation of Infection for Different COVID Populations
State Active Cases Recovered Quarantine Death
Susceptible tracked (St) Oriented Oriented Oriented Oriented
Non-oriented Non-oriented Non-oriented Non-oriented
Susceptible (S) Oriented Oriented Oriented Oriented
Exposed (E) Oriented Oriented Oriented Oriented
Suspected (P) Oriented Oriented Oriented Oriented
Infectious (I) Oriented Oriented Oriented Oriented
Confirmed (C) Oriented Oriented Oriented Oriented
COVID-induced death (D) Yes Yes Yes Induced
No No No Other causes
 var A R Q D 
 
 St 0.36 0.24 0.39 0.01 
 S 0.19 0.33 0.48 0.00 
P1 =  E 0.11 0.69 0.20 0.00  Transition matrixes (2.15)
 
 P 0.10 0.38 0.47 0.05 
 I 0.40 0.36 0.11 0.13 
 C 0.53 0.13 0.22 0.12 
 
The reproduction R0 number will be multiplied with the transition matrix (Table 2.5).
2.7 O
ptimization of COVID Cases from Transition Matrix
Exposed cases on first wave
= 2.5(0.36) + 2.5(0.19) +2.5(0.11) + 2.5(0.10) + 2.5(0.40) + 2.5(0.53) = 4.22 × 10,000 = 4,22000.
Quarantine cases on first wave
= 1.25(0.24) + 1.25 (0.33) + 1.25 (0.69) + 1.25 (0.38) + 1.25 (0.36) + 1.25 (0.13) = 266,250.
Recovered cases on first wave
= 0.75(0.24) + 0.75 (0.33) + 0.75 (0.69) + 0.75 (0.38) + 0.75 (0.36) + 0.75 (0.13) = 159,750.
Death cases
= 2.5(0.01) + 2.5 (0.00) + 2.5(0.00) + 2.5 (0.05) + 2.5 (0.13) + 2.5 (0.12) = 77,500.
2.8 Model Diagnostic Test

The maximum likelihood of the model input = 156.21; R 2 (%) = 0.93.
MC stochastic model is fairly common and relatively estimates the COVID-19 geomet-
ric progression considering different state variables (Azizi et al., 2020). They are being
used in different traits ranging from epidemiological and impact transition parameters.
The state variables were assumed to estimate various transition matrixes to know the
impact of diseases. Overall, hidden Markov models are conceptually quite intuitive and
are very accessible in that they can be implemented without the use of any advanced sta-
tistical or mathematical interventions or concepts (Azizi et al., 2020). There is a great way
to induct the deep learning process of COVID by various time-varying probability dis-
tributions. The probability distribution of state transition is typically represented as the
Markov chain transition matrix. If in the MC model, we consider “N” possible states, the
matrix will be i × n such that entry (i, j) is the probability of transitioning from state “i to
j”. Additionally, the transition matrix must be a stochastic matrix, a matrix whose entries
in each row must add up to exactly unity (Basavarajaiah et al., 2012). This makes complete
sense, since each row represents its own probability distribution (equation 2.3). As per the
model findings, we should know how to optimize the chance of transitioning from one
state to another, but how about the research findings that chance to get transition prob-
abilities occurring from the multiple stages To formulize this intervention, we extrapolate
the probability of forward movement from known state to unknown state over varied
time intervals (e.g., COVID pandemic has been derived from multiple set of state variables;
by these variables, we should estimate the unknown transition probability from known
sources of causative variables). From P1 (equation 2.3) model has derived based on value
of entry of many known variables (i, j) of the matrix propagated by raising “P−1” to the
power of M. For small values of M, this can be easily done by hand with multiplication of
repeated observations or measures. However, for large values of “M”, if you are familiar
with simple mathematical derivation, a more efficient way to increase a matrix to a power
is to first diagonalize the matrix. After obtaining P−1 transition matrix, the reproduction
and presumed values are substituted in every column of transition probability values, and
we should get the predicted values of COVID exposed cases on the first wave. As per the
resultant findings, the asymptotic cases of COVID in the first wave of disease pandemic
was 422,000; quarantine cases 266,250; recovered cases 159,750; and death cases 77,500.
2.9 D iscussion
From the resultant findings of the MC model, there are numerous limitations in presenting
the geometric progression of COVID; at the beginning, we presumed the normalcy of steady
state of COVID. For real instance, some disease traits could change the disease pattern (epi-
demiological and genetic complexity), such as a clinical preexisting stage and comorbid-
ity, and treatment patterns will differ in age-specific criteria (Abdelghafour et al., 2020). In
these cases, the probability transition matrix would also change from one place to another.
Therefore, the MC model demonstrates suitable scenarios in which the disease is exponen-
tially increased or up streaming and necessary prevention programs are implemented by
the concerned national and international authorities. In the future studies, we are intended
to develop a time-varying hidden Markov chain model for the estimation of disease impact
on the health and economic segment (Azizi et al., 2020). However, when compared to steady
hidden Markov chain model iterated Eulerian method, the propagating transition matrix is
less time-consuming because it needs to perform more transient conditions. Therefore, the
present model is superior for the extrapolation of steady-state disease attributes for accurate
prediction of geometric progression (multiplied by reproduction number and hazard rate of
individual attributes). The present model was formulated based on the SIR model approach,
three main attributes such as exposed, asymptomatic, and symptomatic stages linked with
other attributes of cases tracked, treated, untreated, recovered, and death cases.
2.10 Conclusions
This analytical model formulation quickly predicted transient probability matrix consid-
ering multiple epidemiological, clinical, and treatment attributes. Within the scope of this
model inputs, the following conclusions can be drawn: (i) The proposed MC can be used
for predicting detailed information about disease condition and progression, (ii) the for-
mulated model increased the iteration techniques for propagating transient probability
values and consistently maintain accuracy, and (iii) the robustness of the model is more
reliable and there is no complexity for the validation of the model. The next chapter will
deal with RT-PCR and its impact on threshold levels associated with various epidemiologi-
cal, clinical, and demographic attributes. The present model can be applied for the devel-
opment of new mathematical algorithms of RT-PCR (real-time polymerase chain reaction)
for testing COVID-19. It is more suited for classical detection of COVID and other infec-
tious diseases (instead of culture and immunoassays) (Figures 2.13–2.15).
FIGURE 2.13
Schematic plan for model construction.
Problem setup on Covid pandemic
Disease Geometric progression Preventive measures
Before
Confirmation of COVID Outbreak T1 u- T1 u u + T1-k th period w end
FIGURE 2.14
Road map of model formulation.
FIGURE 2.15
Epidemiological model flow chart.
References
Azizi A., Achak D., Aboudi K., Marfak A. Health-related quality of life and behaviour-related life-
style changes due to the Covid-19 home confinement: Dataset from a Moroccan sample J.
Elsevier 2020; 32: 106239. Published online 2020 Aug 27. doi: 10.1016/j.dib.2020.106239.
Basavarajaiah D.M., Narasimha Murthy B. Predictive modeling of autophagy interrelation with fast-
ing. J Biostat Biomet Appl 2020; 5(1): 1–9.
Basavarajaiah D.M., Narasimha Murthy B., Maheshappa K., Leelavathy K. Mathematical model
approach to HIV/AIDS transmission from mother to child. IJSTR 2012; 1(9): 52–61.
Chadsuthi S. Modeling Seasonal leptospirosis transmission and its association with rainfall and tem-
perature in Thailand using time-series and ARIMA analyses. Asian PacJ Trop Med 2012; 5(7):
539–546.
Chatfield C., Yar M. Holt- winters forecasting: Some practical issues. Statistician 1988; 37: 129–140.
Coronavirus Update (Live) Cases and 501644 deaths from Covid-19 virus pandemic – Worldometer,
2020. https://www.worldometers.info/coronavirus/ 10101998.
Costagliola D., Flahault A., Galinec D., Garnerin P., Menares J., Valleron A.J. When is the epidemic
warning cut-off point exceeded. Eur J Epidemiol 1994; 10: 475–476.
De P., et al. Post millennium development goals prospect on child mortality in India: an analysis
using autoregressive integrated moving averages (ARIMA) model. Health 2016; 8: 1845–1872.
doi: 10.4236/health.2016.815176.
Dominici F., Sheppard L., Clyde M. Health effects of air pollution: A statistical review. Int Stat Rev
2003; 71: 243–276.
Healy M.J. A simple method for monitoring routine Statistics. Statistician 1983; 32: 347–349.
Jackson M.J., Baer A., Painter I., Duchin J. A simulation study comparing aberration detection algo-
rithms for syndromic surveillance. BMC Med Informat Decis Mak 2007; 7: 6.
Kotwal A., Yadav A.K., Yadav J., Kotwal J., Khune S. Predictive models of Covid-19 in India: A rapid
review. Med J Armed Forces India Online Pub 2020. doi: 10.1016/j.mjafi.2020.06.001.
Sahai A.K., Rath N., Sood V., Singh M.P. ARIMA modelling & forecasting of Covid-19 in top five
affected countries. Diabetes Metab Syndr 2020; 14(5): 1419–1427.
Scintillant Surveillance Center Open Platform. https://www.cdc.gov/coronavirus/2019-ncov/
your-health/covid-by-county.html.
Serfling R. Methods for current statistical analysis of excess pneumonia-influenza deaths. Publ Health
Rep 1963; 78: 494–506.
Shewhart W.A. 1931. Economic Control of Quality of Manufactured Product. Van Nostrand Reinhold:
Princeton, NJ.
Shmueli G., Burkom H. Statistical challenges facing early outbreak detection in biosurveillance.
Technometrics 2010; 52: 39–51.
Stern L., Lightfoot D. Automated outbreak detection: A quantitative retrospective analysis. Epidemiol
Infect 1999; 122: 103–110.
Stroup D., Wharton M., Kafadar K., Dean A. Evaluation of a method for detecting aberrations in
public health surveillance data. Am J Epidemiol 1993; 137: 373–380.
Unkel S., Farrington C.P., Garthwaite P.H., Robertson C., Andrews N. Statistical methods for the pro-
spective detection of infectious disease outbreaks: A review. J Roy Stat Soc 2011; 175(1): 49–82.
Wang B., Li Y., et al. Mathematical modeling and epidemic prediction of Covid-19 and its significance
to epidemic prevention and control measures. Ann Infect Dis Epidemiol 2020; 5(1): 1052.
3
Study of Anxiety and Fear of COVID-19
3.1 Introduction
The COVID-19 disease spreads from one person to another primarily through droplets
released when someone is sick, sneezes, or coughs, which can land on the mouth or nose
of the people nearby, and through close physical contacts with someone sick, such as hug-
ging or shaking hands (Zhang et al., 2020; Zhong et al., 2020; Wang et al., 2020). WHO
declared nCov as a pandemic on March 2020 (Zhang et al., 2020), which gregariously
affected approximately 7.30 million individuals among which 0.16 million have lost their
lives and 2.03 million individuals are still suffering from debilitating nCov2019 (WHO,
Dec 2020). People of all age groups are infected by this new virus; older people and people
with preexisting medical conditions (such as asthma, diabetes, CVD, and hypertension)
appear to be more vulnerable and become severely ill with virus (Li W et al., 2020). WHO
advises people of all age groups to take steps to protect themselves from the virus, by
practicing good hand hygiene and good respiratory hygiene (Varshney et al., 2020; Singh
and Subedi, 2020). Coming to the virus outbreak, the virus might have seeded outside the
China and subsequently got localized, which is inevitable unless some kind of draconian
measures were taken at global level, viz. cancellation of mass gathering, closure of schools,
insisting to work from home, and lockdown (Saurabh and Ranjan, 2020; Shigemura et al.,
2020; Shereen et al., 2020). Since the containment measures failed to halt the spread of virus
in the epidemic area, the local transportation was arranged for the purpose of relocation
of susceptible people to a safe place (Shigemura et al., 2020; Roy et al., 2020; Ramaci et al.,
2020; Gao et al., 2020). A lot of measures were taken during the previous major pandemics,
e.g., SARS, MERS, or pandemic influenza, and could serve as useful cited information for
the implementation of causative measures on health policy at global level (Rana et al., 2020;
Goyal et al., 2020). Many studies cited that psychological problems and fear are the most
important consequences in terms of mental health, including stress, anxiety, depression,
and uncertainty, which emerged progressively during the COVID-19 outbreak (Zhonghua
et al., 2020; Li W et al., 2020). A common psychological augmentation related to the mass
quarantine, which was imposed in order to attenuate the pandemic spread, is general-
ized fear and pervasive community anxiety, which are only increased with the addition
of every new case. The situation was further worsened by anxiety-provoking information
aired through social media (Kang et al., 2020). The psychological reaction to COVID-19
pandemic may vary from a panic behavior or collective hysteria to pervasive feelings of
hopelessness and separation, which are associated with negative outcomes including sui-
cidal behavior and also impact the overall quality of life (Lai et al., 2020). While the lock-
down mitigates the impact of coronavirus on the population, it has dire implications on
DOI: 10.1201/9781003204794-3 101

economic and allied activities. Government and non-governmental organizations/private

sectors/companies need to coordinate in a holistic way to address the fine nuances of this
crisis (Kelly et al., 2019). COVID-19 has also sparked off an impending economic crisis and
recession (Huang et al., 2020). Social distancing, self-isolation, and travel restrictions have
led to a reduced workforce across all economic sectors and led many to lose their jobs (Guo
et al., 2016; Goyal et al., 2020). Schools have been closed down, and the need for manufac-
tured products for comorbidities has declined (Firouzbakht et al., 2021). In contrast, the
need for medical supplies for the management of pandemic has significantly increased
at global platform (Dsouza et al., 2020). The food sector is also facing increased demand
due to panic buying and stockpiling of food grains, cereals, and necessary food products
(Asmundson and Taylor, 2020). In the context of the global pandemic, the entire planet is
under the grip of an undeclared emergency (lack of food for human beings and domestic
animals). All these consequences have led to fears, worries, and anxiety among individu-
als worldwide (Asmundson and Taylor, 2020). As per the literature, the fear is the central
emotional in response to imminent threats such as the COVID-19. This pandemic of the
novel coronavirus has increased the anxiety and fear experienced by human beings irre-
spective of age group (Brooks et al., 2020; Abuhammad et al., 2020). The anxiety and fear
have been increasing in the elderly, children, pregnant women, and persons with comor-
bidities. Furthermore, during the COVID outbreak, social media platforms have become
active sites for the dissemination of conspiracy theories that provide alternative expla-
nations of the cause of the pandemic, such as secret insight by powerful and malicious
groups (Ahorsu et al., 2020). However, the association of individuals’ beliefs in conspiracy
theories about COVID-19 with mental health and well-being issues has been investigated
in selected sites. The cited literature is very limited worldwide for taking curative mea-
sures and exploring health policies to frame control measures for COVID-19 pandemic. In
this paradigm, the present study is an attempt to document the stigma and fear of COVID
and the effect of diseases on well-being of human beings. The outcome of the research will
be more beneficial for health policymakers, planners, epidemiologists, clinical psycholo-
gists, and healthcare professionals for taking right decision with respect to the psychologi-
cally depressed population.
3.2 Methods
An online survey was performed during the pandemic of COVID-19 using a non-probability
snowball sampling technique. The questionnaire was validated and comprised of demo-
graphic characteristics regarding fear and anxiety as per the fear scale (FCV-19S). A total
of 650 respondents were selected from the database of social platform. We have randomly
chosen the respondents from the total population based on the proportional allocation
method. We categorized the respondents based on the demographic criteria. As per the
categorization, the respondents were grouped into two: The first group included frontline
healthcare workers such as medical doctors, dentists, nursing professionals, and pharma-
cists, and the second group was general public. The structured questionnaire was sent
through e-mail and electronic gadgets confidentially with security password (on line mon-
key survey method). Before the inception of survey, we obtained informed consent from
each of the participants through digital signature. Electronically, we requested all the par-
ticipants to fill in the questionnaire without any overlapping information. The structured
Study of Anxiety and Fear of COVID-19 103
questionnaire format included open- and closed-ended questions; for each question, dif-
ferent rates were assigned (0–5 scale). The level of agreement on each statement of ques-
tions was indicated by using five-point Likert scale. Answers included strongly disagree
coded as 0, disagree coded as 1, neutral coded as 2, agree coded as 3, and strongly agree
coded as 4. For each question, the minimum score and maximum score were 1 and 5. The
total score was calculated by adding up the scores of all individual items ranging from
10 to 50. The higher the score, the greater the fear of coronavirus. The collected data were
analyzed by using Minitab software. Logistic regression and ROC analyses were done at
the greatest accuracy for compilation of data sets. The cutoff value was calculated based
on the sensitivity analysis. The level of agreement was tested by the modified Kappa scale.
3.3 Results
Scientifically, fear is an adaptive invasive response in the presence of dangerous situation.
As per the literature available, we opine that the infectious threat is an uncertain and
continuous process, as in the current situation of COVID-19 pandemic at global level, fear
can become chronic and worrisome. In the present study, we identified the level of fear in
mixed population and also formulated a new model to explore the predictors of fear of the
novel coronavirus. We have grouped the population into G1: frontline healthcare workers
and G2: general population. A total of 455 (70%) respondents were selected from Group
1 and 195 (30%) respondents were selected from the general population (software engi-
neers, businessmen, government employees, students, etc.). The age group was classified
based on mean and SD. Majority of the respondents expressed were in the age group of
41–45 years: 130 (28.57%), followed by 36–40 years: 102(22.42%); anxiety score was found to
be statistically significant (p < 0.01; Table 3.1) between all age groups of frontline healthcare
workers and general population. By using logistic predictive models, we predicted the fol-
lowing psychological vulnerability factors such as intolerance of uncertainty (70%; odds
4.55; p < 0.01); worry and health anxiety (82%; odds 11.25; p < 0.01); media exposure (63%;
odds 6.32; p < 0.01); and personal relevance (23%; odds 0.75; p >0.01) (i.e., personal health,
risk to loved ones, and risk control). The study found that health anxiety, regular media,
and social media were seen as risk factors that increase the anxiety level (95th percentile
mean score was 9.15 with SD 0.22) (Table 3.2).
Fear is a functional adaptive emotional feeling that was driven by the inherent soul,
which can mobilize the energy to deal with the potential threat of pandemic. However,
fear is well calibrated to the actual threat; many people suffer from COVID outbreak
threat. It can be manifold risk factors for decreasing the life cycle of the healthcare workers
and general public in many places. For instance, when fear is too excessive, it will have det-
rimental changes on both body and mind (the person may grid with mental health prob-
lems, phobia, and social anxiety). On the other hand, social media and watching TV and
news may cause chronic depression and anxiety at individual level. This may also result
in harm to health sectors (due to people ignoring government measures to slow down the
spread of novel coronavirus or due to reckless policies that ignore the risks). Furthermore,
fear and anxiety trigger behavioral changes among public and healthcare workers that
can mitigate certain threats, but paradoxical changes may be seen in that particular popu-
lation. Table 3.3 shows how different time intervals breach the fear and anxiety levels
in individual population. The study found that 1–2 hours odds 3.60; 3–4 hours odds 4.58;
104
TABLE 3.1
Correlation between Anxiety Score and Age of the Respondents
Frontline Healthcare Workers General Public
Age Group (Years) < 9 Score >9 Score Total P-value < 9 Score >9 Score Total P-Value
20–25 06 (1.32%) 29 (6.37%) 35 (7.69%) ≤0.01 5 (2.056%) 13 (6.67%) 18 (9.23%) ≤0.01
26–30 03 (0.66%) 33 (7.25%) 36 (7.91%) ≤0.01 06 (3.08%) 06 (3.08%) 12 (6.15%) ≤0.01
31–35 10 (2.20%) 88 (19.34%) 98 (21.54%) ≤0.01 09 (4.62%) 26 (13.33%) 35 (17.95%) ≤0.01
36–40 22 (4.84%) 80 (17.58%) 102 (22.42%) ≤0.01 12 (6.15%) 86 (44.10%) 98 (50.26%) ≤0.01
41–45 26 (5.71%) 104 (22.86%) 130 (28.57%) ≤0.01 03 (1.54%) 22 (11.28%) 25 (12.82%) ≤0.01
46–50 28 (6.15%) 26 (5.71%) 54 (11.857%) ≤0.01 02 (1.03%) 05 (2.528%) 07 (3.59%) ≤0.01
Total 95 (20.88%) 360 (79.12%) 455 (100.0%) 37 (18.97%) 158 (81.03%) 195 (100%)
COVID Transmission Modeling
TABLE 3.2
Level of Anxiety and Phobia of COVID-19 by Confounding Effect of Watching TV/Social
(watch per day)
Time Interval Geometric Mean Score Conditional Logistic P-Value CI 95%
0–1 hours 1.25 ≥0.64 [0.85–2.10]
1–2 hours 3.60 ≥0.13 [1.36–4.98]
3–4 hours 4.58 ≤0.00 [2.17–5.69]
5–6 hours 4.98 ≤0.00 [3.11–6.55]
>6 hours 6.79 ≤0.00 [4.02–8.79]
TABLE 3.3
Multiple Linear Regression—Actual, Interpolation, and Residuals
Time or Index Actual Interpolation Forecast Residuals Prediction Error
0–1 hours 1.25 0.9665 0.2836
1–2 hours 3.6 4.006 −0.4062
3–4 hours 4.58 4.93 −0.3503
5–6 hours 4.98 5.213 −0.2335
>6 hours 6.79 6.084 0.7064
5–6 hours odds 4.98; and >6 hours odds 6.79 and was statistically significant to anxiety and
having negative impact on person or individual (p < 0.01).
The determinants were analyzed by using logistic and multiple regression analyses. The
results revealed that the rate of change of geometric mean of anxiety in each group of
population was (+27.55 SD: 12.82). Living status was assessed from the data sets, and the
logistic regression was employed (dependent variable anxiety score <9 was coded as 0 and
>9 was coded as 1). Exogenous variable on living status, employment status, comorbidity,
smoking status, alcoholic consumption, frequency of alcoholic consumption, and eating
behavior were considered for the analysis. The results found that all exogenous variables
are statistically significant (p < 0.01) at 1% level of significance. Descriptive statistics are pre-
sented in Table 3.4: living status of respondents without family 185 (28.46%), employment
status 236 (36.30%), comorbidity 552 (84.92%), smoking 292 (44.92%), alcoholic consump-
tion 352 (54.51%), frequency of alcoholic consumption 375 (57.63%), eating behavior eat less
health 256 (39.38%), unchanged or healthier 394 (60.61%), physical activity never stopped
457 (70.30%), and unchanged or exercise more 193 (29.69%), respectively. OLS regression
analysis was employed to know the significance of sleeping, BMI, and coping factor score.
Research findings revealed that underweight (BMI < 18.5) 193 (29.69%) (p < 0.01); normal
weight (18.5 ≤ BMI < 25.0) 135 (20.76%); and overweight/obese (BMI ≥ 25.0) 322 (49.53%) (p
<0.01). The underweight and overweight were seen to be significantly correlated with anxi-
ety and depression. Sleeping factors and coping factors were also positively correlated
with psychological impacts of respondents.
Amid COVID-19 pandemic, situation in India worsened post-lockdown period. COVID-
19 has badly affected, and it has exerted great pressure on vigor as well as the psychologi-
cal well-being of the infected person and family members and lowering the quality of life
(QOL) Majority of family members of health professionals were suffering from depression.
The prevalence of depression was 78.56%, and anxiety and fear prevalence was (84.0%).
Limited resources, global economic crunch, negative movement of national GDP, illiteracy,
TABLE 3.4
Multiple Linear Regressions—Ordinary Least Squares
Variable Parameter Two-Tailed P-Value
Geometric score of anxiety +27.55 SD:12.82 0.1647
Living status
Without family 185 (28.46%)
With family 465 (71.53%) ≤0.001
Employment status
Yes 236 (36.30%) ≤0.001
No
Comorbidity 552 (84.92%) ≤0.001
Yes
No 292 (44.92%) ≤0.001
Smoking
Yes 352 (54.15%) ≤0.001
Alcoholic status
Yes 375 (57.63%) ≤0.001
Increases drinking last 4 weeks
Health services use in the last 4 weeks
Level of fear of COVID
Low score (7–21)
Sleeping +3.873 SD3.72 0.04071
Coping factor −0.6257 SD 0.46 0.03102
BMI, kg/m2
Underweight (BMI < 18.5) 193 (29.69%) ≤0.001
Normal weight (18.5 ≤ BMI < 25.0) 135 (20.76%) ≤0.001
Overweight/obese (BMI ≥ 25.0) 322 (49.53%)
Eating behavior
Eat less health 256 (39.38%) ≥0.001
Unchanged or healthier 394 (60.61%) ≤0.001
Physical activity
Never, stopped, or exercise less 457 (70.30%) ≤0.001
Unchanged or exercise more 193 (29.69%) ≤0.001
myths and not following the proper protocol, non-advocacy of government policy may
have increased the risk of depression in everyone, and anxiety and fear among frontline
healthcare professionals. Anxiety is a common response to any stressful situation and
it is the fear of the unknown and it may have multiple consequences. The online sur-
vey was conducted during the first wave of COVID-19 pandemic. The FCV-19S validated
scale was used for collection of data from the selected respondents of frontline healthcare
workers and general public. Each facet of the questionnaire was validated, and score was
assigned to the categorical variables of each facet of FCV-19 Scale. The collected data sets
were reanalyzed using R statistical software; structural stochastic convergence and logis-
tic regression model were employed to know the convergence between the variables of
general public and COVID frontline healthcare professionals. As per the results portrayed
in Table 3.5, most afraid of COVID pandemic (odds 5.62; p < 0.01); makes uncomfortable to
think about COVID (odds 3.55, CI 95% 0.22–0.91); My hands become clammy when I think
about COVID-19 (odds 8.74, P < 0.01, CI 95% 0.34–0.84); afraid of losing my life because of
COVID-19 (odds 6.28; p < 0.01, CI 95% 0.29–0.96); watching news and stories about COVID-
19 on social media, become nervous/anxious (odds 10.25; CI 95% 0.12–0.88); Cannot sleep
because I am worrying about getting COVID (odds 4.98; CI 95% 0.28–0.87, P < 0.01) and
TABLE 3.5
Convergent Validity Fear Effects of the FCV-19 Scale
Items Odds Ratio CI 95% P-Value
I am most afraid of COVID 5.62 0.65–0.89 ≤0.001
It makes me uncomfortable to think about COVID 3.55 0.22–0.91 ≤0.001
My hands become clammy when I think about COVID-19 8.74 0.34–0.84 ≤0.001
I am afraid of losing my life because of COVID-19 6.28 0.29–0.96 ≤0.001
When watching news and stories about COVID-19 on social 10.25 0.12–0.88 ≤0.001
media, I become nervous/anxious
I cannot sleep because I am worrying about getting COVID 4.98 0.28–0.87 ≤0.001
My heart races/palpates when I think about getting COVID-19 1.28 0.47–0.74 ≤0.001
My heart races/pulpits palpates when I think about getting COVID-19 (odds 1.28; CI 95%
0.47–0.74, P < 0.01).
Stigma is a mark of disgrace associated with a particular circumstance, quality, or per-
son; during the pandemic of COVID-19, stigma and discrimination shot up to threshold
level at global level. The COVID-19 stigma measures the degree of evaluation and dis-
crimination that impacted people in the COVID-19 pandemic. This indicator was analyzed
to know the accurate level of stigma and discrimination among people. The study was
carried out by administering a structured questionnaire—FCV-19 Scale. It was directly
administered to the people previously infected or people exposed to COVID-19 despite
taking prior preventive measures such as wearing mask and maintaining social distanc-
ing. This assessment tools will consists of three components: discrimination, acceptance
of COVID-19 previously infected and individuals who exposed to them such as healthcare
providers, and fear (the eigenvalue for discrimination was 2.55, alpha 0.91; the eigenvalue
for acceptance was < 1, alpha 0.44; and the eigenvalue for fear of COVID was 2.98, alpha
0.81). Simultaneously, we assessed the various characteristics of COVID fear from FCV-19
Scale (Table 3.6). The logistic regression was employed to know the significance of various
stigma and fear attributes (the dependent variable person infected was coded as 1 and non-
infected coded as 0). The following exogenous criterion variables were used for testing the
hypothetical statement: The fear of reliving a pandemic if you have lived through another
infectious disease pandemic/epidemic in your lifetime (such as Nipah, Ebola or SARS).
This facet of the questionnaire was agreed by 78.57% of the respondents (Wald: −0.1 to
−1.6, p < 0.01); respondents showing disagreement was 21.43% (Wald: −0.40 to −1.97, p < 0.01).
The fear of losing livelihood due to isolation or marked limitation of travel and social
behavior (applies to those in small scale industries in the travel, fitness, food or tourism
sectors): respondents that showed the agreement level of Very likely was 50% (Wald: −0.3
to −1.3, p < 0.01); Likely, 31.25% (Wald: −0.60 to −1.6, p < 0.01); Unlikely, 12.50% (Wald: −1.9 to
−3.70, p < 0.01); and Very unlikely, 6.25% (Wald: −0.90 to −1.70, p > 0.01). A constant sense of
insecurity for oneself and loved ones: Strongly agree (50.0%; Wald: −0.50 to −1.71, p < 0.01);
Agree (25.0%; Wald: −1.7 to −3.50, p <0.01); Neither agree nor disagree (12.50%; Wald: −0.70
to −1.50, p > 0.01); Strongly disagree (12.50%; Wald: −0.70 to −1.50, p.0.01). Anxiety of social
or physical distancing resulting in lack of contact with family or friends who may be living
far away. For some it’s the other way round: getting huddled for the first time with a large
family resulting in mixed emotions: Extremely useful (25%; Wald: −1 to −3.50, p < 0.01); Very
useful (18.75%; Wald: −3.20 to −6.25, p < 0.01); Somewhat useful (43.75%; Wald: −0.70 to −1.9,
p < 0.01); and Somewhat useful (12.50%; Wald: −0.70 to −1.50, p > 0.01). The phobia of COVID-
19 going out of home: Strongly agree (31.25%; Wald: −0.70 to −1.60, p < 0.01); Agree (50.0%;
TABLE 3.6
Characteristics of Various Attributes Associated with Stigma and Fear of COVID
Attributes Percentage Wald Sequential Test P-Value
1. The fear of reliving a pandemic if you have 78.57% −0.1 to −1.6 ≤0.01
lived through another infectious disease 0.00% - -
pandemic/epidemic in your lifetime (such as 21.43% −0.40 to −1.97 ≥0.01
Nipah, Ebola or SARS).
a. Agree
b. Strongly agree
c. Disagree
2. Fear of losing livelihood due to isolation or 50.00% −0.3 to −1.3 ≤0.01
marked limitation of travel and social 31.25% −0.60 to −1.6 ≤0.01
behavior (applies to those in small scale 12.50% −1.9 to −3.70 ≥0.01
industries in the travel, fitness, food or 6.25% −0.90 to −1.70 ≥0.01
tourism sectors).
Very likely
Likely
Unlikely
Very unlikely
3. A constant sense of insecurity for oneself and 50.00% −0.50 to −1.71 ≤0.01
loved ones. 25.00% −1.7 to −3.50 ≤0.01
Strongly agree 12.50% −0.70 to −1.50 ≥0.01
Agree 12.50% −0.70 to −1.50 ≥0.01
Neither agree nor disagree
Strongly disagree
4. Anxiety of social/physical distancing 25.00% −1 to −3.50 ≤0.01
resulting in lack of contact with family or 18.75% −3.20 to −6.25 ≤0.01
friends who may be living far away. For some 43.75% −0.70 to −1.9 ≤0.01
it’s the other way round: getting huddled for 12.50% −0.70 to −1.50 ≥0.01
the first time with a large family resulting in 0.00%
mixed emotions.
Extremely useful
Very useful
Somewhat useful
Not so useful
Not at all useful
5. The phobia of COVID-19 going out of home. 31.25% −0.70 to −1.60 ≤0.01
Strongly agree 50.00% −0.30 to −1.30 ≤0.01
Agree 0.000% - ≥0.01
Neither agree nor disagree 12.50% −2.0 to −3.70 ≥0.01
Disagree 6.250% −1.30 to −2.40
Strongly disagree
6. How stigma toward people with symptoms 43.75% −0.40 to −1.30 ≤0.01
such as cold, cough or sneezing, which might 31.25% −0.70 to −1.60 ≤0.01
just be a simple flu. 18.75% −1.10 to −2.30 ≤0.01
Always 6.251% −1.30 to −2.40 ≥0.01
Usually 0.00% -
Sometimes
Rarely
Never
(Continued)

Characteristics of Various Attributes Associated with Stigma and Fear of COVID
Attributes Percentage Wald Sequential Test P-Value
7. The compulsive need to hoard food, 13.33% −0.70 to −1.40 ≤0.01
essentials or medical supplies such as 40.00% −0.80 to −2.10 ≤0.01
antibiotics, analgesics, anti-allergic 20.00% −3.0 to −5.90 ≥0.01
medicines, face masks, sanitizers for 26.67% −1.6 to −3.40 ≥0.01
prevention of COVID-19. 0.00% -
Very easy
Easy
Neither easy nor difficult
Difficult
Very difficult
8. How psychological stress over the growing 18.75% −0.60 to −1.20 ≥0.01
panic, which compounds daily, many times 31.25% −2.10 to −4.30 ≥0.01
due to reinforced messaging in all forms of 50.00% −0.70 to −2.2 ≤0.01
media.
Better
About the same
Worse
9. How electronic media will affect the 78.00% −0.0 to −1.20 ≤0.01
well-being of life with respect to COVID-19 12.00% −7.50 to −13.60 ≤0.01
intervention. 10.00% −0.90 to −1.70 ≥0.01
Very likely 0.00% -
Likely
Unlikely
Very unlikely
10. How likely is it that you would recommend 80.00% −0.10 to −1.50 ≤0.01
in healthcare workers, paramedics, and 20.00% −0.90 to −1.90 ≤0.01
volunteers, virologists or media persons at 0.00% -
the front line of the COVID-19 control or 0.00% -
coverage: fatigue, burnout, frustration or the
fear of contracting or guilt of transmitting
infection? To a friend or colleague?
Very likely
Likely
Unlikely
Very unlikely
Detractors 36%; passives 64%; promoters 0.00%; NET Score 19.
Wald: −0.30 to −1.30, p < 0.01); Disagree (12.50%; Wald: −2.0 to −3.70, p > 0.01); and Strongly
disagree (6.25%; Wald: −1.30 to −2.40, p > 0.01). How stigma (The people can fear of common
flu) toward people with symptoms such as cold, cough or sneezing, which might just be
a simple flu: Always (43.75%; Wald: −0.40 to −1.30, p < 0.01); Usually (31.25%; Wald: −0.70 to
−1.60, p < 0.01); and Sometimes (18.75%; Wald: −1.10 to −2.30, p < 0.01). The compulsive need
to hoard food, essentials or medical supplies such as antibiotics, analgesics, anti-allergic
medicines, face masks, sanitizers for prevention of COVID-19: Very easy (13.30%; Wald:
−0.70 to −1.40, p < 0.01); Easy (40.0%; Wald: −0.80 to −2.10, p,0.01); and Neither easy nor dif-
ficult (20.0%; Wald: −3.0 to −5.90, p > 0.01). The psychological stress over the growing panic,
which compounds daily, many times due to reinforced messaging in all forms of media:
Better (18.75%; Wald: −0.60 to −1.20, p > 0.01); About the same (31.25%; Wald: 2.10 to −4.30,
p > 0.01); and Worse (50.0%; Wald: −0.70 to −2.2, p < 0.01). How electronic media will affect
the well-being of life with respect to COVID-19 intervention: Very likely (78.0%; Wald: −0.0
to −1.20, p < 0.01); Likely (12.0%; Wald: −7.50 to −13.60, p < 0.01); and Unlikely (10.0%; Wald:
−0.90 to −1.70, p > 0.01). Lastly, we assessed the following: How likely is it that you would
recommend in healthcare workers, paramedics, and volunteers, virologists or media per-
sons at the frontline of the COVID-19 control or coverage: fatigue, burnout, frustration or
the fear of contracting or guilt of transmitting infection? To a friend or colleague: Very
likely (80%; Wald: −0.10 to −1.50, p < 0.01).
The virus can spread from an infected person to a normal person through droplets. The
research intervention is increasing to explore the exact mechanism of virus. Many of the
carriers of the virus show absolutely no symptoms and we call them as hidden carriers
and they are the bridge population and spread the infection very fast. Usually, the virus
can spread through droplets as well as direct contact with infected persons. Therefore,
personal preventive measures are very important for self-protection as well as a duty of all
citizens in the interest of health emergency (Table 3.7). Among the individuals, preventive
behavior characteristics were analyzed by using multivariate analysis. The most empha-
sized ones were the following: people practiced hygiene in the manner of washing of
hands, the Frequency wash hands with Soap and Soap at least 10 minutes (5.0%; odds 0.56
[0.12–0.88]). The maximum frequency was seen in 30–60 minutes (80.78%; odds 3.56 [2.5–
4.85, p < 0.01]), followed by before eating (98.99%; odds 3.87 [1.25–4.22]). Mean interval of
frequency clean and disinfected the touched objects and surface the home and work envi-
ronment: 3.58 ± 1.22 (odds 1.74 [0.85–2.01, p < 0.01]); People who showing the Interest for self-
isolation (65.22%; odds 2.88 [1.17–3.22, p < 0.01]); Healthcare system would be panic (89.55%;
odds 6.85 [4.22–7.55, p < 0.01]); Easy available personal protective equipment (28.50%; odds
0.17 [0.11–0.22], p > 0.01); Social distancing (26.92%; odds 3.01 [2.50–3.85]); and Wearing
masks (83.65%; odds 6.22 [3.11–8.01, p < 0.01]) will be significantly reduced the infection rate
TABLE 3.7
Behavioral Characteristics of COVID-19 response
Characteristics % Odds Ratio [CI 95%] P-Value
i) General hygiene
Frequency wash hands with Soap and Soap at least 10 5.0 0.56 [0.12–0.88] ≥0.001
minutes 6.22 0.89 [0.2–1.25] ≤0.001
< 30 minutes 8.00 0.88 [0.47–1.02] ≥0.001
30–60 minutes 80.78 3.56 [2.5–4.85] ≤0.001
>1 hour 34.28 4.22 [3.16–5.88] ≤0.001
After coughing and sneezing 7.48 0.55 [0.17–0.74] ≥0.001
After touching nose and eyes 19.22 0.74 [0.22–0.92] ≥0.001
After caring for the sick 47.0 0.82 [0.27–0.98] ≥0.001
Before, after and during food preparation 96.0 1.22 [0.98–1.58] ≥0.001
Before eating 98.99 3.87 [1.25–4.22] ≤0.001
After using the toilet 15.54 4.25 [3.85–5.50] ≥0.001
After handling animals or animal wastes 0.28 [0.17–0.33]
Mean interval of frequency clean and disinfected the 3.58 ± 1.22 1.74 [0.85–2.01] ≤0.001
touched objects and surface the home and work
environment
Interest for self-isolation 65.22 2.88 [1.17–3.22] ≤0.001
Social distancing 26.92 0.61 [0.55–0.98] ≥0.001
Healthcare system would be panic (yes) 89.55 6.85 [4.22–7.55] ≤0.001
Easy available personal protective equipment (Yes) 28.0 0.17 [0.11–0.22] ≥0.001
Wearing masks 83.65 6.22 [3.11–8.01] ≤0.001
TABLE 3.8
Personal Stress Level Before and After Pandemic of SARS-Cov-19 (0–10 Dundee Stress Scale)
Stress Mean Score
(0–10 Scale)
Stress Mean ±SE Odds Ratio [CI 95%] P-Value
Stress before pandemic 2.86 ± 0.12 0.88 [0.21–1.22] 0.701
Stress as a result of pandemic 8.13 ± 0.67 3.64 [1.55–4.88] ≤0.000
Concern about personally being exposed to 9.88 ± 0.25 6.88 [3.10–10.22] ≤0.000
COVID-19
Concern about family members exposed to 8.69 ± 0.32 5.12 [2.56–7.93] ≤0.000
COVID-19
Online survey conducted, June 2020, Department of Statistics and Computer Sciences, KVAFSU.
Dundee stress scale (0–10) was used to test the personal stress level before and after
the pandemic of COVID-19. Weighted logistic regression model was used to compile the
data sets. As per the resultant findings, the mean score of the Stress before pandemic was
2.86 ± 0.12 (odds 0.80 [0.21–1.22]) and found to be statistically insignificant. The mean score
of Stress as a result of pandemic was 8.13 ± 0.67 (odds 3.64 [1.55–4.88, p < 0.01]); Concern
about personally being exposed to COVID-19 mean score was 9.88 ± 0.25 (odds 6.88 [3.10–
10.22, p < 0.01]), and Concern about family members exposed to COVID-19 mean score was
8.69 ± 0.32 (odds 5.12 [2.56–7.93, p < 0.01]) (Table 3.8).
3.4 Discussion
The present study discusses different level of fear and anxiety of COVID-19. The anxiety,
stress, and psychological depression and their possible differences were estimated from
the frontline healthcare workers and general public (mixed population). The results clearly
envisage that the respondents at younger and middle age groups show high level of stress,
anxiety, and depression. These findings show that a major psychological impact on quality
life and general well-being of younger population (age group 40–50 years) exists among
mixed population of public and frontline healthcare professionals. During the COVID-19
pandemic lockdown, which is consistent with the moderate augmentation seen in front-
line healthcare workers besides mild symptoms of anxiety, stress in the early stage of the
pandemic (Ahorsu et al., 2020; Abuhammad et al., 2020). However, fear is well calibrated
to actual threat, many people suffering from COVID outbreak threat, it can be manifold
risk factors to decline the overall well-being of quality of life. Social media and watching
TV news will deliberately affect the negative psychological feelings of the person suffering
with anxiety (Brooks et al., 2020; Asmundson and Taylor, 2020; Doshi et al., 2020). The con-
ditions in which frontline healthcare workers and general public cope with the pandemic
are extremely affecting the life in many ways. The rapid spread of the disease, the large
number of people affected in the first and second waves with increased number of deaths,
mistrust of the health system, ignorance, and disinformation may all have contributed
significantly to the fact that both population experience fear and anxiety of COVID-19.
This fear has been a important factor that influences depression and the effect of this fear
on increased trend of depression could be worsened by the existence. Healthcare profes-
sionals experience a higher chance of exposure to risk and face extreme workloads, moral
dilemmas, and rapidly varying working environment climax at the same time. Majority of
the healthcare professionals extraordinary stress among healthcare providers during the
rapid outbreak of COVID-19 and high infection risk, understanding, stigmatization and
uncertainty, comprehensive supports of government polices after the intervention of first
wave of disease (Dsouza et al., 2020; Firouzbakht et al., 2021). Speedy spread and severity of
various symptoms of the novel virus have severely affected the global economy, especially
the health care and food industry globally. Despite the fear of getting infected, COVID
frontline healthcare workers have discharged their duties with highest affectionate and it
shows good spirit of dedication and unity during the pandemic to fight against the virus.
Remarkably, global lockdown was imposed to control infection and many national health
authorities drafted COVID-19 pandemic guidelines and prevention strategies to control
the geometric progression of disease (Basavarajaiah et al., 2012). In other words, social
distancing and promotion of preventive behaviors are very important solutions to break-
ing the chain of virus and also flattening of disease dynamic curve (Goyal et al., 2020).
Many government organizations including non-governmental organizations (NGOs) are
educating the people about the concepts of public and health emergency crisis and pro-
mote preventive behaviors among them, which in turn leads to the full-blown limitation
of the disease spread (Guo et al., 2016; Huang et al., 2020). Hence, it is necessary to edu-
cate and equip the public community with proper precautions to control the outbreak.
Moreover, due to social distancing and limited physical contact, Web-based interactions
with healthcare professionals and proper announcement of disease impact can reduce the
burden of COVID infection (Kelly et al., 2019). A significant relation was seen in general
hygiene, sleeping and preventive measures economic status, education and the preventive
behaviors of hand washing, wearing masks and protective gloves had reduced the infec-
tion. On the other hand, the present study noticed that the level of anxiety is more in both
healthcare professionals and general public due to social stigmatization and phobia (Lai et
al., 2019; Kang et al., 2020; Li S et al., 2016; Li W et al., 2020; Lee et al., 2020). Stigma is a mark
of disgrace associated with a particular circumstance, quality, or person. During the pan-
demic of COVID-19, stigma and discrimination shot up to the threshold level at global level
(Zhonghua et al., 2020; NIMHANS, Bengaluru 2020). The COVID-19 stigma measures the
degree of evaluation and discrimination that impacted people in the COVID-19 pandemic.
Kelly et al. (2019) studied the predictors among survivors from pandemics and found that
the recovered people aged 20–40 were more likely to experience the risk of stigma, but in
our study, the stigma is more in elderly population (50–60 years) (Ornell et al., 2020; Qiu
et al., 2020; Rana et al., 2020; Reynolds et al., 2008; Goyal et al., 2020; Gao et al., 2020). One
plausible explanation may be the lack of information of the emerging infectious disease
and how to handle the situation. Large-scale infectious disease outbreaks of high severity
are still uncommon in most of the countries. The solution to this problem will be by dis-
semination of health information in an appropriate and accurate manner among media
and virtual platforms.
FIGURE 3.1
Index of anxiety score.
3.5 Conclusions
The present study concludes that there is a high level of anxiety, fear, and stigma among
healthcare professionals and general population. Practicing stable mental health by spiri-
tual manner, family supports, psychological counseling is essential and play a significant
role in strengthening immunity fight against COVID-19. In addition to that, certain prac-
tical measures such as inception of post-exposure prophylaxis and family health insur-
ance for COVID-induced death need to be taken to decrease the fear and anxiety level in
selected population. Resource-poor countries should address the key issues and imple-
ment control measures at the early stage of infection and highly concentrated on health
professionals preparedness during the intervention of COVID-19 (Figures 3.1 and 3.2).
FIGURE 3.2
QOL correlation with anxiety score.
References
Ahorsu D.K., Lin C.Y., Imani V., Saffari M., Griffiths M.D., Pakpour A.H. The fear of Covid19 Scale:
Development and initial validation. Int J Ment Health Addiction 2020; 23(3): 45–51.
Abuhammad S., Khabour O.F., Alzoubi K.H. Covid‐19 contact‐tracing technology: acceptability and
ethical issues of use. Patient Prefe Adherence 2020; 14: 1639.
Asmundson G.J.G., Taylor S. Coronaphobia: Fear and the 2019-nCoV outbreak. J Anxiety Disord 2020;
70: 102196.
Brooks S.K., Webster R.K., Smith L.E., Woodland L., Wessely S., Greenberg N. The psychologi-
cal impact of quarantine and how to reduce it: Rapid review of the evidence. Lancet 2020;
395(10227): 912–20.
Basavarajaiah D.M., Narasimha Murthy B., Leelavathy B., Maheshappa K. Assessment of quality of
life of people living with HIV/AIDS in Karnataka State. IJSTR 2012; 1(10): 38–47.
Doshi D., Karunakar P., Sukhabogi J.R., Prasanna J.S., Mahajan S.V. Assessing coronavirus fear in
Indian population using the fear of Covid‐19 scale. Int J Mental Health Addict. 2020; 31: 1.
Dsouza D.D., Quadros S., Hyderabadwala Z.J., Mamun M.A. Aggregated Covid-19 suicide inci-
dences in India: Fear of Covid-19 infection is the prominent causative factor. Psych Res 2020;
290: 113145.
Firouzbakht M., Omidvar, S., Firouzbakht S. Covid-19 preventive behaviors and influencing factors
in the Iranian population; a web-based survey. BMC Public Health 2021; 21: 143.
Gao J., Zheng P., Jia Y., Chen H., Mao Y., Chen S. Mental health problems and social media exposure
during Covid-19 outbreak. Plos One 2020; 15(4): e0231924.
Goyal K., Chauhan P., Chhikara K., Gupta P., Singh M.P. Fear of Covid 2019: First suicidal case in
India! Asian J Psych 2020; 49: 101989.
Guo X., Meng Z., Huang G., Fan J., Zhou W., Ling W. Meta-analysis of the prevalence of anxiety
disorders in mainland China from 2000 to 2015. Sci Rep 2016; 6(1): 28033.
Huang Y., Zhao N. Generalized anxiety disorder, depressive symptoms and sleep quality during
Covid-19 outbreak in China: A web-based cross-sectional survey. Psych Res 2020; 288: 112954.
Kang L., Ma S., Chen M., Yang J., Wang Y., Li R. Impact on mental health and perceptions of psycho-
logical care among medical and nursing staff in Wuhan during the 2019 novel corona virus
disease outbreak: A cross-sectional study. Brain Behav Immun 2020; 87: 11–17.
Kelly J.D., Weiser S.D., Wilson B. Ebola virus disease‐related stigma among survivors declined in
Liberia over an 18‐month, post‐outbreak period: An observational cohort study. PLoS Negl Trop
Dis. 2019; 13(2): 7185.
Lai J., Ma S., Wang Y., Cai Z., Hu J., Wei N. Factors associated with mental health outcomes among
health care workers exposed to corona virus disease 2019. JAMA Network Open 2020; 3(3):
203976.
Li S., Li L., Zhu X., Wang Y., Zhang J., Zhao L. Comparison of characteristics of anxiety sensitivity
across career stages and its relationship with nursing stress among female nurses in Hunan,
China. BMJ Open 2016; 6(5): 010829.
Li W., Yang Y., Liu Z.-H., Zhao Y.-J., Zhang Q., Zhang L. Progression of Mental health Services dur-
ing the Covid-19 outbreak in China. Int J Biol Sci 2020; 16(10): 1732.
Lee S.A. Coronavirus anxiety scale: A brief mental health screener for Covid-19 related anxiety.
Death Stud 2020; 44(7): 393–401.
Novel Coronavirus Pneumonia Emergency Response Epidemiology. The epidemiological charac-
teristics of an outbreak of 2019 novel corona virus diseases (Covid-19) in China. Zhonghua Liu
Xing Bing Xue Za Zhi 2020; 41(2): 145. doi: 10.3760/cma.j.issn.0254-6450.2020.02.003.
National Institute of Mental Health and Neurosciences. Mental Health in the Times of Covid-19
Pandemic Guidance for General Medical and Specialised Mental Health Care Settings; 2020.
Available at: https://nimhans.ac.in/wp-content/uploads/2020/04/MentalHealthIssuesCOVID-
19NIMHANS.pdf.
Ornell F., Schuch J.B., Sordi A.O., Kessler F.H. Pandemic fear and Covid‐19: Mental health burden
and strategies. Braz J Psych 2020; 42(3): 232–235.
Qiu J., Shen B., Zhao M., Wang Z., Xie B., Xu Y. A nationwide survey of psychological distress among
Chinese people in the Covid-19 epidemic: Implications and policy recommendations. General
Psych 2020; 33(2): 156–158.
Rana W., Mukhtar S., Mukhtar S. Mental health of medical workers in Pakistan during the pandemic
Covid-19 outbreak. Asian J. Psych 2020; 51: 102080.
Reynolds D.L., Garay J.R., Deamond S.L., Moran M.K., Gold W., Styra R. Understanding, compliance
and psychological impact of the SARS quarantine experience. Epidemiol Infect. 2008; 136(7):
997–1007.
Ramaci T., Barattucci M., Ledda C., Rapisarda V. Social stigma during Covid‐19 and ITS Impact on
HCWs outcomes. Sustainability. 2020; 12(9): 3834.
Roy D., Tripathy S., Kar S.K., Sharma N., Verma S.K., Kaushal V. Study of knowledge, attitude, anx-
iety & perceived mental healthcare need in Indian population during Covid‐19 pandemic.
Asian J Psych 2020; 8: 102083.
Shereen M.A., Khan S., Kazmi A., Bashir N., Siddique R. Covid-19 infection: origin, transmission,
and characteristics of human corona viruses. J Adv Res 2020; 24: 91–98.
Shigemura J., Ursano R.J., Morganstein J.C., Kurosawa M., Benedek D.M. Public responses to the
novel 2019 corona virus (2019‐nCoV) in Japan: Mental health consequences and target popula-
tions. Psych Clin Neurosci 2020; 74(4): 281.
Saurabh K., Ranjan S. Compliance and psychological impact of quarantine in children and adoles-
cents due to Covid-19 pandemic. Indian J Pediatr 2020; 87(7): 532–6.
Singh R., Subedi M. Covid‐19 and stigma: Social discrimination towards frontline healthcare pro-
viders and Covid‐19 recovered patients in Nepal. Asian J Psychiatr 2020; 53: 102222.
Varshney M., Parel J.T., Raizada N., Sarin S.K. Initial psychological impact of Covid-19 and its cor-
relates in Indian community: An online (FEEL-Covid) survey. Plos One. 2020; 15(5): e0233874.
Wong L.P., Sam I.-C. Temporal changes in psycho behavioral responses during the 2009 H1N1 influ-
enza pandemic. Prev Med 2010; 51(1): 92–3.
Wang C., Pan R., Wan X., Tan Y., Xu L., McIntyre R.S. A longitudinal study on the mental health
of general population during the Covid-19 epidemic in China. Brain Behav Immunity 2020; 87:
40–8.
Zhong B.-L., et al. Knowledge, attitudes, and practices towards Covid-19 among Chinese residents
during the rapid rise period of the Covid-19 outbreak: A quick online cross-sectional survey.
Int J Biol Sci 2020; 16(10):1745–52.
Zhang Z., et al. Protecting healthcare personnel from 2019-nCoV infection risks: Lessons and
Suggestions. Front Med 2020; 14: 1–3.
4
COVID-19 Gene Sequencing Modeling
4.1 Introduction
DNA gene sequencing is the process of determining the nucleic acid sequences, in other
words nucleotides in DNA (Forster et al., 2020; Chen et al., 2020). It includes any methods or
technologies that are used to determine the order of the four nucleotide bases (base pairs):
adenine, guanine, cytosine, and thymine. DNA sequencing is to explore the various orders
of the four chemical building blocks called bases that make up the DNA molecule. The
sequence provides scientists the kind of genetic information that is carried in a particular
gene segment. For example, scientists can use sequence information to determine which
stretch of the DNA contains genes and which stretch carries regulatory instructions to turn
on or off genes. Furthermore, sequence data can highlight the changes in a gene that may
cause disease. As per the established fact, in the DNA double helix, the four chemical bases
always bond with the same partner to form “base pairs.” Adenine always pairs with thymine;
cytosine always pairs with guanine (Figure 4.1). This pairing is the basis for the mechanisms
by which DNA molecules are copied when cells divide, and the pairing also undermines
the methods by which most DNA sequencing experiments are done. The human genome
contains 3 billion base pairs that spell out the instructions for making and for maintain-
ing a human being. Nowadays, due to the rapid growth of research interventions on DNA
FIGURE 4.1
Differences between RNA and DNA.
DOI: 10.1201/9781003204794-4 117

sequencing, scientists are able to determine conditions that impact health. DNA sequencing
can provide a precise diagnosis of a disease, e.g., COVID-19, SARS, and Zika virus, and help
us in the effective management of disease during pandemic and epidemic situations. It can
provide treatment options for both symptomatic and asymptomatic stages. Another advan-
tage of genome sequencing is that information regarding drug efficacy or adverse effects of
drug use can be obtained. DNA sequencing allows the scientists to use the genetic informa-
tion in different research domains such as medical, agricultural, veterinary, animal, and
fisheries sciences, including forensic science for tracing culprits involved in a crime.
4.2 M axam and Gilbert Method

In 1976–1977, Allan Maxam and Walter Gilbert developed a DNA sequencing method
based on chemical modification of DNA and subsequent cleavage at specific bases. The
following steps are used in the MG method:
• Chemical modification of DNA—radioactive labeling at one 5’-end of the DNA

(typically by a kinase reaction using [gamma-32P]ATP)
• Purification of the DNA fragment to be sequenced
• Chemical treatment generates breaks in DNA
• Run on the gel
• Chemical modification—polynucleotide kinase radioactive labeling at one 5’-end
of the DNA using gamma-32P
• 5′ G A C GT GC A A CGAA 3′
• 32P 5’ G A CG T GC AA CG AA 3′
• Base modification was done by using dimethyl sulfate
• Purine—adenine and guanine
• Only DMS yield G
• DMS + formic acid: yield G+A
• After the above-said process, we can cleave sugar phosphate using piperidine
• Base modification was done by using hydrazine
• Pyrimidine—cytosine and thymidine
• Only hydrazine: C+T
• Hydrazine + NaCl: C
• After the above-said process, we can cleave sugar phosphate using piperidine.
4.3 Sanger Sequencing

It is also known as the chain termination method. It is a method for determining the
nucleotide sequence of DNA and was developed by the two-time Nobel laureate Frederick
Sanger and his colleagues in 1977, hence the name the Sanger sequencing. The method of
gene sequencing involves the following three steps (Figure 4.2).
COVID-19 Gene Sequencing 119
FIGURE 4.2
Maxam–Gilbert sequencing read from bottom to top 5′ to 3′.
4.3.1 Chain Termination PCR

The first step of PCR is to explore the DNA sequence of interest, which is used as a tem-
plate, called chain termination PCR. Chain termination PCR works just like standard PCR,
but with one major difference, the addition of modified nucleotides (dNTPs) called dide-
oxyribonucleotides (ddNTPs). In the extension step of standard PCR, DNA polymerase
adds dNTPs to a growing DNA strand by catalyzing the formation of phosphodiester
bond between the free 3’ OH group of the last nucleotide and the 5’ phosphate of the next
base. The result of chain termination PCR is generation of millions to billions of oligo-
nucleotide copies of the DNA sequence of interest, terminated at a random length (n) by 5’
ddNTPs (Figure 4.3).
FIGURE 4.3
Steps in Sanger sequencing method.
FIGURE 4.4
Challenges and opportunities in long-read sequencing.
4.3.2 S eparation Based on Size Using Gel Electrophoresis

In the above step, with the intervention of ddNTPs, the chain is terminated and oligo-
nucleotides are separated by size through gel electrophoresis. In gel electrophoresis, DNA
samples are loaded into one end of a gel matrix, and an electric current is applied; DNA is
negatively charged, so the oligonucleotides will be pulled toward the positive electrode on
the opposite side of the gel. Because all DNA fragments have the same charge per unit of
mass, the speed at which the oligonucleotides move will be determined only by size. The
smaller the fragment, the lesser the friction it will experience as it moves through the gel
and the faster it will move. As a result, the oligonucleotides will be arranged from smallest
to largest, reading the gel from bottom to top (Figure 4.4).
4.3.3 A nalysis of Gel and Identification of DNA Sequence

The last step simply involves reading the gel to determine the sequence of the input DNA,
because DNA polymerase only synthesizes DNA in the 5’ to 3’ direction starting at a pro-
vided primer. Each terminal ddNTP will correspond to a specific nucleotide in the original
sequence. Therefore, by reading the gel bands from smallest to largest, we can determine
the 5’ to 3’ sequence of the original DNA strand (Forster et al., 2020). In manual Sanger
sequencing, the user reads all four lanes of the gel at once, moving from bottom to top,
using the lane to determine the identity of the terminal ddNTP for each band. For example,
if the bottom band is found in the column corresponding to ddGTP, then the smallest PCR
fragment terminates with ddGTP and the first nucleotide from the 5’-end of the original
sequence has a guanine (G) base. In case of automated sequencing, a computer reads each
band of the capillary gel, in order, using fluorescence to determine the identity of each
terminal ddNTP. In short, a laser excites the fluorescent tags in each band and a computer
detects the resulting light emitted. Because each of the four ddNTPs is tagged with a dif-
ferent fluorescent label, the light emitted can be directly tied to the identity of the terminal
ddNTP. The output is called a chromatogram, which shows the fluorescent peak of each
nucleotide along the length of the template DNA.
4.4 Long-Read Sequencing Methods

i. Single-molecule real-time (SMRT) sequencing
ii. Nanopore DNA sequencing
iii. Massive parallel signature sequencing (MPSS)
iv. Polony sequencing
v. Pyrosequencing
vi. Illumina (Solexa) sequencing
vii. Combinatorial probe anchor synthesis
viii. SOLiD sequencing (Figure 4.5).
FIGURE 4.5
Various generations of DNA sequencing.
4.4.1 Single-Molecule Real-Time (SMRT) Sequencing

DNA sequencing is a process of reading part or all of the DNA of an organism, helping to
improve clinical, diagnostic care across different areas of medicine. In case of agricultural
science, identification of transgenic gene, candidate gene, signature gene, etc., is necessary
for the improvement of crop production and sustainable yield to resolve the food scarcity
across the globe. The long-read sequencing describes the potential of DNA sequencing tech-
nologies for diagnostic sequencing in clinical setting and, in this context, the challenges in
implementing the technology. The two dominant producers of true long-read sequencing
technologies are Pacific Biosciences (Pacbio) and Oxford Nanopore Technologies. The first
commercially available long-read single-molecule platform was the RS system based on
PacBio’s SMRT sequencing technology, which has since evolved into their RSII and Sequel
System. SMRT sequencing is constitutional and capsulize the microbial and viral genetic
testing, including reproductive, cancer, and other associated diseases.
As per the literature, long-read sequencing provides massive reads to overcome various
computational difficulties surrounding the assembly of genomes, transcript reconstruc-
tion, and metagenomics compared to the current-generation sequencing technologies. LR
sequencing offers many advantages over short reads or second-generation sequencing
techniques, further driving the market growth (Li H, 2018; Li et al., 2020). For instance,
long reads generated by SMRT sequencing provide a comprehensive overview of the
entire genome and are used to distinguish genetic and structural variants. The long-read
sequencing market size was estimated at $973.60 million in 2019 and is expected to grow
with a CAGR of 24 percent, on account of increasing R&D investment by governments
and market players on long-read sequencing technologies. The SMRT sequencing segment
holds the highest market share as it helps in achieving high accuracy due to low system-
atic biasness and long-read lengths (Phelan et al., 2020). The consumable segment held the
largest market share in 2018 owing to the regular procurement of consumable items by the
end users. The key players of long-read sequencing techniques are Pacific Biosciences of
California, Inc., Oxford Nanopore Technologies Limited, Future Genomics Technologies
B.V., Garvan Institute of Medical Research, Quantapore, Inc., Stratos Genomics, Inc.,
Institute of Integrative Biology of the Cell (I2BC), Genome transcriptome facility of
Bordeaux, Takara Bio, Inc., MicrobesNG, BaseClear B.V., and NextOmics.
4.4.2 Nanopore DNA Sequencing

DNA can be sequenced by threading it through a microscopic pore in a membrane. Bases
are identified by the way they affect ions flowing through the pore from one side of the
membrane to the other. A unique shape of each DNA base causes a characteristics disrup-
tion in the electrical current, providing a readout of the underlying sequence. The nano-
pore creates a hole in the membrane as the current passes through the nanopore, this
creates a disruption in the current, and this disruption is interpreted to understand and
identify the sequence (Figures 4.6 and 4.7).
4.4.3 M erits of Nanopore DNA Sequencing
• Direct DNA and RNA sequencing.

• No capital cost.
• High-throughput sequence.
• Ultralong reads.
• The sequences are scalable.
FIGURE 4.6
Methods of long-read sequencing by nanopore sequencing. (a) Poring procedure for high throughput sequencing.
(b) Sugar Phosphate group distributed distributed in Open pore current.
• Same core technology.

• Real-time, simple, and rapid process.
• Current–voltage alpha hemolysis:
I (t ) =
1
∆tLz ∑ q (t + ∆t ) − Z t
i=1
i i (4.1)
4.4.4 Massive Parallel Signature Sequencing (MPSS)

MPSS is an open-ended platform that analyzes the level of gene expression in a sample
by counting the number of individual mRNA molecules produced by each gene. The bac-
teria-free bead-based library preparation, the Megaclone technology, was developed by
Sydney Brenner. In MPSS, mRNA transcripts de novo, the gene with low level expression
could be quantified by MPSS (Rockett et al., 2020). All clones in a macro-bead library can
be sequenced simultaneously (the so-called massively parallel). The data produced in a
digital format are captured by counting all mRNA molecules in tissue or cell samples.
FIGURE 4.7
Frame of long-read sequencing by nanopore sequencing.
In MPSS, all genes are analyzed simultaneously and bioinformatics tools are used to sort
out the number of mRNA from each gene relative to the total number of molecules in the
sample. Even genes that are expressed at low levels can be quantified with high accu-
racy; the counting of mRNA with MPSS is obtained based on its unique ability to identify
every mRNA in a sample by generating a 17-bp sequence for each mRNA at specific sites
upstream from its poly(A) tail. This 17-bp sequence is used as an mRNA identification
signature. We can measure the level of expression of any given gene, and the total num-
ber of signatures for that gene’s mRNA is counted. MPSS data sets involve one million
or more signature sequences. They have the sensitivity to accurately quantify genes that
are expressed at very low level within a cell. No other single technology has such a per-
formance characteristic. A total of 1819 unique MPSS signatures matching the antisense
strands of 1605 non-reluctant unique clusters (such as APOC1, APCO2, APOB, and APOH)
were highly expressed in hepatocytes. As per the human genomic study, MPSS deter-
mines the transcriptome of 32 normal human tissues and it finds the pattern of expres-
sion of almost 20,000 genes with high sensitivity and specificity. The differences in genes
expression between cell and tissue types are largely determined by transcripts derived
from a limited number of tissue-specific genes (Lu R et al., 2020).
NO T E : MPSS is considered as the first of the “next-generation” sequencing technologies.
MPSS was developed in the 1990s at Lynx Therapeutics, a company founded in 1992 by
Sydney Brenner and Sam Eletr. Data are set out in an ultrahigh-throughput sequencing
technology. When applied to expression profile, it can reveal almost every transcript in the
sample and provide its accurate expression level. However, the MPSS was a bead-based
method that uses a complex approach of adapter ligation followed by adapter decod-
ing, reading the sequence in increments of four nucleotides; this method is susceptible
to sequence-specific biasness or loss of specific sequences. The essential properties of the

MPSS output were typical of later “next-gen” data types, including hundreds of thousands
of short DNA sequences. In case of MPSS, these were typically used for sequencing cDNA
for the measurement of gene expression levels.
4.4.5 Statistical Methods for Testing MPSS Data

MPSS data set is categorical from statistical point of view, which enables the large number
of measurements of a given signature in the data sets (typically 10–10,000 or more) as well
as the size of the entire data sets (typically over one million) to be evaluated irrespective of
whether the particular given signature is differently expressed in multiple different sam-
ples or not. The Z-test is employed for the analysis of sequential data sets and to know the
differential gene expression between two samples. For example, if X1 + X2 represents the
abundance of a specific signature in Samples 1 and 2, respectively, where n1,2 represents
the total number of signatures generalized for all mRNA in Samples 1 and 2, the propor-
tion of P1 = X1/n1; P2 = X2/n2 each follows a binomial distribution.
 1 1
N ( P1 , P2 ) , pq  +  (4.2)
 n1 n2 
where the unknown parameters p and q can be estimated as
 x + x2 
pˆ =  1 ; qˆ = ( 1 − pˆ ) (4.3)
 n1 + n2 
Equation (4.1) shows an inverse relationship between the level of expression and size of
the difference that can be evaluated between samples. However, BD tends to be Poisson
distribution (PD); the large sequencing data are expressed in a selected individual sample
by a model of expression given below.
e−λ λ x
P ( X = xi ) = λ→∞ (4.4)
x!
where xi = 1,2,3…nth number of observation expression repeated;

λ = np ; p = λ p. This is the probability of gene expression abundance.
Another method of representation of expression of similar gene is to express in both the
groups by applying the Venn graphical diagram to visualize the expression data in condi-
tional format (Hoffmann et al., 2020). A Venn diagram is a graphical representation of sets
or groups of elements or IDs in the form of circles where common elements/IDs of the sets
are represented by the area of overlap among the circles. In bioinformatics, it is a popular
graphical representation to compare subsets; for example, when running a pairwise differ-
ential expression analysis, it might be interesting to rapidly visualize the expressed genes
that overlap between different groups (control v/s treatment, etc.). OmicsBox offers a Venn
diagram tool that allows to select multiple ID lists or ID value lists in text or OmicsBox for-
mat and to draw the intersection of the elements of the lists as a Venn diagram. Figure 4.8
describes the four components, and each component is represented in a common format
of unique values of the OmicsBox of significantly differentially expressed genes (SDEGs)
(diagnosis, incipient, moderate, and severe).
FIGURE 4.8
Four-set Venn diagram of the overlap of significantly differentially expressed genes (SDEGs) in GSE28146 gene
expression datasets.
4.5 Cauchy Distribution
a
The model of Cauchy p( x) = (4.5)
(
π x + a2
2
)
The Cauchy or Lorentz PDF describes the disease spectrum by diffusive modes of the dis-
ease and is given as follows (Figure 4.9 and Table 4.1):
FIGURE 4.9
QQ plot of Cauchy distribution.
TABLE 4.1
Estimated Values of Scale and Location Parameters
of Cauchy Distribution
Parameter Estimated Value Standard Deviation
Location 63.38 1.09
Scale 4.55 1.23
∞
a
f (k) =
∫ exp
−∞
( − ikx )
(
π x + a2
2
dx
)
(4.6)
∞
1  1 1 
=
2 πi ∫
exp( − ikx ) 
−∞
−
 x − ia x + ia 
dx (4.7)
4.6 Exponential Distribution
X i = ( i = 65, 63, 70, 63, 68, 64, 78, 76, 63, 68, 64, 63, 62, 60, 58, 63, 64, 65, 78, 82, 84, 74, 86, 83, 54,
56, 54, 58, 59, 53, 52 )
Exponential distribution is used for the estimation of rate of gene expression in human
genomic analysis. In probability theory and statistical science, the exponential distribution
is the probability distribution of the time between events in a Poisson point process. It is a
gamma distribution process in which sequencing event occurs continuously and indepen-
dently at a constant average rate. We consider Xi as the random variable, the gene expressed
in a locus (above data sets). We formulated an exponential distribution for exploring the
rate of gene expression in a particular locus. The following mathematical derivations are
used for estimating the rate of gene expression (Table 4.2).
 λ expo− λ x x≥0
f ( x, λ ) =  (4.8)
 0 x<0
f ( x , λ ) = the probability density function of gene expression;
λ = rate of expression;
x = random variable (take the values of expression).
TABLE 4.2
Estimated Value of Rate of Infection by Exponential
Distribution
Rate 0.015 0.0027
FIGURE 4.10
QQ plot of exponential distribution.
 0.02 expo−0.02*65 x≥0

f ( x, λ ) =  (4.9)
 0 x<0
f ( x , λ ) = 1.5% expression variation observed in the first series of data (Figure 4.10).
4.7 Gamma Distribution

In genomic analysis, we often impose various theoretical and practical assumptions to be
drawn from the real data sets of genome, wherein the gene expression data follow a spe-
cific kind of distribution to estimate rationalized quotients (Harmer et al., 2002). However,
we have rarely modeled the estimation of shape and scale parameters of gene expression
changes in a specific locus. We consider Xi as a random variable, the gene expressed in a
locus (the above data sets). We formulated an exponential distribution for exploring the
rate of gene expression in a particular locus (Figure 4.11 and Table 4.3):
γ −1
 x − µ  x − µ
expo  –
 β   β 
f ( x) = x ≥ µ; β > 0 (4.10)
βΓγ
γ = shape parameter;
µ = location parameter;
β = scale parameter.
FIGURE 4.11
QQ plot of gamma distribution.
TABLE 4.3
Estimated Values of Shape and Location Parameters
of Gamma Distribution
Shape 50.56 12.80
Rate 0.76 0.194
4.8 L og-Normal Distribution

The log-normal distribution has important applications in gene expression and cell theory.
It is widely used in computational biology, wherein the gene expression data sets follow
continuous distribution of random variables whose logarithms are distributed normally.
In other words, the log-normal distribution is generated by the function of e X , where x (ran-
dom variable of gene expression) is supposed to be normally distributed. In the natural
logarithm of e X , the logarithms of log-normally distributed random variables are normally
distributed. Function f(x) is the new gene expression, which is normally distributed x > 0
and σ > 0 ; µ = log ( m ), where µ is the mean value of new gene expression (log value has
been taken). The density function of overall genomic expression was modeled in the fol-
lowing equation.
2
e −( ln x ) 2σ 2
f ( x) = (4.11)
xσ 2 π
e −( ln x−θ − µ ) /2σ
2 2
f ( x) = x > 0, σ > 0 (4.12)

( x − θ )σ 2 π
where µ = the explicit scale parameter and σ is the standard deviation of the log of the dis-
tribution, which is also called the shape parameter. The shape parameter generally affects
the overall shape of the log-normal distribution, but it does not impact the location and
height of the graph and the mean “µ” of the distribution. Also known as the scale param-
eter, θ is the location likelihood parameter that is used to locate the graph on the x-axis
(Table 4.4).
A common salient problem in statistical genomics is how to organize expression data
from genes that have been determined to exhibit differential expression relative to vari-
ous cellular states. Cells in a time course experiment may exhibit such genes, as many
cells in any sort of designed experiments or observational expression were modeled
based on gamma distribution, the formulated model (Rad et al., 2020; Rockett et al., 2020)
(Figure 4.12).
TABLE 4.4
Estimated Mean and SD Values of Log-Normal
Distribution
Mean log 4.18 0.025
SD log 0.13 0.017
FIGURE 4.12
QQ plot of log-normal distribution.
4.9 L ogistic Distribution

The logistic regression distribution model is very popular in cell and computational biol-
ogy. It is currently popular in demographic and economic modeling because it is similar
to the Gaussian normal distribution, but it is somewhat more peaked. It does not appear
often in risk analysis modeling (Table 4.5 and Figure 4.13).
z  x−α 
f ( x) = Where z = exp  − (4.13)
β (1 + z )
2
 β 
The parameterized restriction β > 0 and the mean = α.
TABLE 4.5
Estimated Values of Location and Scale Parameters
of Logistic Distribution
Location 65.25 1.72
Scale 5.472 0.82
FIGURE 4.13
QQ plot of logistic distribution.
4.10 Poisson Distribution

The rate of (“X” random variable) viral gene expression is considered as infinity, the prob-
ability of infection is very small, and the geometric progression of the disease was simu-
lated using the following model:
e−λ λ x
P(X = x) = ( x = 1, 2, 3…..n) (4.14)
x!
λ = mean of the virus expression; λ = np;

x = random replication of virus (Table 4.6 and Figure 4.14).
TABLE 4.6
Estimated Value Rate of Infection (λ)
Lambda 66.129 1.460
FIGURE 4.14
QQ plot of Poisson distribution.
4.11 Weibull Distribution Model

The Weibull distribution model was formulated to know the failure rate of disease. Scale
and shape parameters were considered for the model demonstration by real data of
COVID-19. The formula for the probability density function (PDF) of the three-parameter
Weibull distribution is as follows (Table 4.7 and Figure 4.15):
β
β −1  t −γ 
β  t−γ  −
 η 
f ( x) =  expo (4.15)
η  η 
where f ( x ) ≥ 0, x ≥ γ .
The PDF formula of the two-parameter Weibull distribution is as follows:

β
β −1  t
β t − 
f ( x) =   expo η
(4.16)
η η
TABLE 4.7
Estimated Values of Shape and Scale Parameters of
Weibull Distribution
Shape 7.144 0.95
Scale 70.37 1.87
FIGURE 4.15
QQ plot of Weibull distribution.
4.12 Next-Generation Sequencing

Scientifically, NGS is a powerful segment that has deeply enabled the sequencing of thou-
sands of millions of DNA molecules simultaneously. It is also known as high-throughput
sequencing, and it is to catch all terms used to describe a number of different modern
sequencing technologies in defined time intervals. Usually, NGS is low-cost sequencing,
which has a driven mechanism capable of propagating thousands of millions sequences at
once (MacLean et al., 2020; Neher and Shraiman, 2011; Phelan et al., 2020). It is intended to
lower the cost of DNA sequencing beyond what is possible with standard dye terminator
methods. Thus, these recent technologies allow us to determine or estimate the sequence
of DNA and RNA at a rapid phase yet economical than the previously used Sanger
sequencing. Furthermore, NGS has revolutionized the study of genomics and advanced
molecular biology, cell biology, and biotechnological interventions. We classified different
generations; the NGS has led to overcoming the certain limitations of conventional DNA
sequencing methods and has found usage in a wide range of molecular biology applica-
tions. The generation has been classified into four groups (Figure 4.16).
4.13 I llumina Solexa Sequencing

It is an advanced method of high-throughput sequencing technique, and it has been used
to sequence many genomes and has enabled the comparison of DNA sequences to improve
the understanding of health and disease. The method of sequencing crunches and reads
millions of highly accurate reads, making it much faster and economical than other meth-
ods (Mercatelli et al., 2020) (Figures 4.17 and 4.18).
FIGURE 4.16
Histogram of transformed data from genomic analysis.
FIGURE 4.17
DNA fragmentation and library preparation.
FIGURE 4.18
Illumina Solexa sequencing technique.
4.13.1 Procedure for Illumina Sequencing
i. The first step in this sequencing technique is to break up the DNA into more man-
ageable fragments of around 200–600 base pairs (Figure 4.19).
ii. Short sequences of DNA adaptors are attached to the DNA fragments.
iii. The DNA fragments attached to adaptors are then made single-stranded. This is
done by incubating the fragments with sodium hydroxide.
iv. Once so prepared, the DNA fragments are washed across the flow cells. The com-
plementary DNA binds to primers on the surface of the flow cell, and the DNA
that doesn’t attach is washed away.
v. The DNA attached to flow cell is then replicated to form small clusters of DNA
with the same sequence. When sequenced, each cluster of DNA molecules will
emit a signal that is strong enough to be detected by a camera.
vi. Unlabeled nucleotide bases and DNA polymerase are then added to lengthen and
join the strands of DNA attached to the flow cell. This creates bridges of double-
stranded DNA between the primers on the flow cell surface.
vii. The double-stranded DNA is then broken down into single-stranded DNA using
heat, leaving several million dense clusters of identical DNA sequences.
viii. Primer and fluorescently labeled terminators (terminator versions of nucleotide
bases A, C, G, or T that terminate the synthesis of DNA) are added to the flow cells.
ix. The primer attached to the DNA is sequenced.
FIGURE 4.19
Overview of massive parallel signature sequencing techniques.
x. The DNA polymerase then binds to the primer and adds the first fluorescently
labeled terminator to the new DNA strand. Once a base has been added, no more
bases can be added to the strand of DNA until the terminator base is cut from the
DNA.
xi. Laser is passed over the flow cell to activate the florescent label on the nucleotide
base. This fluorescence is detected by a camera and recorded on a computer. Each
of the terminator bases (A, C, G, and T) give off a different color.
xii. The fluorescently labeled terminator group is then removed from the first base,
and the next fluorescently labeled terminator base is added alongside. And so, the
process continues until millions of clusters are sequenced (Table 4.8).
xiii. The DNA sequence is analyzed base by base during Illumina sequencing, making
it a highly accurate method. The sequence generated can then be aligned to a refer-
ence sequence; this looks for matches or changes in the sequenced DNA (Figures
4.20 and 4.21).
TABLE 4.8
Different Platforms of Solexa Sequencing
Methods Bp Reads
Solexa 1G 18 bp reads, ~1Gbp/run
Illumina GA 36 bp reads ~3Gbp/run
Illumina GAII 75 bp paired ends ~10Gbp/run (8 days)
Illumina GAIIx 75 bp paired end reads ~40Gbp/run (8 days)
Illumina HiSeq 2000 100 bp paired end reads ~200 Gbp/run (10 days
Illumina HiSeq, v3 SBS 100 bp paired end reads ~600Gbp/run (12 days)
Illumina HiSeq 2500 (Rapid) 150 bp paired end reads ~ 180 Gbp/run (2 days)
MiSeq 250 bp paired end reads ~8 Gbp/run (2 days)
FIGURE 4.20
Sequencing by synthesis.
FIGURE 4.21
Flowchart of Illumina sequencing.
NO T E : The central line is the median value, the yellow box represents the IQR, the upper
and lower whiskers represent 10% and 90% points, and the blue line represents the mean
quality. Figure 4.22 describes the categorization of quality score; trimming of unwanted
and low-profile score is the preliminary course of action. The analysis was done de novo
using the Illumina–GenBank virtual platform. Sequences were read at positions fixed
at 100% quintiles. The sequences quality is a function of the number of counting per
megabase (counting Ns as gaps) and the number of nonstandard bases per genome. The
sequences quality score varied among different sources (Figure 4.22); as per the analysis,
the quality score should be attained at a maximum threshold value, i.e., >38. However, if
the score is <35, then the genome is said to be not perfect, while 3% of the WGS genomes
received had perfect scores (0.99 or better). Despite being draft, as might be expected, the
collection of COVID genomes had higher quality scores, with a maximum sequences qual-
ity of 0.96 and an average of (Figure 4.23). All other databases had an average score of 0.82
or better. The WGA scored high enough on sequence quality and is considered as a better
move in COVID genomes, so additional analyses were not done on these genomes (Liao
et al., 2020; Lu et al., 2020; Mann et al., 2014).
FIGURE 4.22
Quality scores across all bases—Illumina 1.90 coding.
FIGURE 4.23
Illumina reads quality scores.
4.14 Model Formulation

The quality score is the numerical value that is assigned at confidence to a particular base
within a read. Some sequencers have their own propriety quality encoding, but most have
adopted Phred encoding. Each quality score represents the probability of an incorrect base
call at the position (Table 4.9).
Label base =T Q =25
Phred + 33 ASCII = 0 + 33 = 33
<36—Low score, removed.
Statistically, the forecasting model is useful to know the seasonal and random effects of
ASCII and Phred scores because gene sequencing is heavily concentrated on the predictive
modeling approach to describe the future course of action. In this section, we formulate a
new model on the whole genomic sequences and predict the seasonality effect of the qual-
ity score. Formally, the exponential smoothing model was demonstrated to explore the
intervention of seasonality of quality score.
Ft+1 = α Yt + ( 1 − α ) Ft (4.17)
where
Ft+1 = forecast of quality score for the next period;
α = the Smoothening constant;
Yt = observed value of quality score series in specific percentile;
Ft = previous forecast for the period of “t”.
The exponential smoothing model was demonstrated to forecast the better-quality score
for further follow-up studies, and the variations among different annotations are extrapo-
lated. Equation (4.17) simulates the entire spectrum of quality score of whole genomes.
Figure 4.24 clearly depicts that the mean autocorrelation function was 40 with a frequency
band width of 0.043. The maximum accuracy of quality score was attained (>0.95), and
theoretical quintiles were normally distributed with mean and common variance.
Figure 4.25 depicts that the observed Phred score and its quality correlated eight times of
relative differences. The observed and forecasted quality scores were found to be perfectly
matched (black color—observed and red color—filtered) (Figure 4.26).
The seasonality of quality score was demonstrated using the decomposition by LOESS
model (Figure 4.27). The seasonal and trend variations were seen in COVID WGA.
Biologically, more virus strains propagated from the environment and replicated new
mutant viruses in different time periods at population level.
Table 4.10 depicts that the quality of a given base call is measured as a Phred quality
score and indicates the probability of the base being called correctly. The score generally
ranges from 2 to 40 with higher scores indicating greater confidence in the call. A common
practice is to filter out bases with Phred scores below 20, although individual preferences
TABLE 4.9
Calculation Procedure of ASCII Score
C C G T C A A T T T A A G T T T T
C C G T C A A T T T A A G T T T T
Label base = T Q = 25
Phred +33 ASCII = 0+33=33
FIGURE 4.24
Quality score assessed by exponential smoothening.
FIGURE 4.25
Extrapolation of Quality score assessed by Exponential smoothening
may lead some researchers to modulate this threshold The removal of redundant reads
and undesired sequences (such as 3’ adaptors, contaminants, or primers) is essential, as
contaminating sequences will not align to the genome, resulting in poor alignment qual-
ity. Trimming low-quality ends from reads is important as current sequencers are highly
error-prone, with a significant dip in base quality at the 3’-ends of reads. With time, it is
likely that such technical issues will be resolved, making it even more cost-effective. Other
preprocessing alternatives include assessing the read GC content. A uniform GC content
FIGURE 4.26
Extrapolation of quality score assessed by exponential smoothening.
FIGURE 4.27
Seasonal decomposition of quality score.
TABLE 4.10
Phred Score Grouping—Predicted Exponential Smoothing Model
Forecast
Percentile Observed Phred Mean Fitted Phred Mean Residual Effect Decision
39 13 16.0 −3.00 Poor score
38 16 17.0 −1.00 Poor score
37 17 18.0 −1.00 Poor score
40 17 13.0 3.99 Poor score
36 18 19.0 −1.00 Poor score
35 19 21.0 −2.00 Poor score
31 21 30.0 −9.00 Poor score
34 21 32.0 −11.00 Poor score
33 23 25.0 −1.99 Poor score
42 24 23.0 1.00 Poor score
42 25 21.0 3.99 Poor score
44 27 23.0 3.99 Poor score
50 30 32.0 −2.00 Poor score
70 32 23.9 8.00 Poor score
70 32 42.0 −10.00 Poor score
70 32 36.0 −3.99 Poor score
70 32 36.0 −4.00 Poor score
70 32 38.0 −5.99 Poor score
70 32 17.0 15.00 Poor score
70 32 35.0 −3.00 Poor score
70 32 36.0 −4.01 Poor score
70 32 43.0 −10.99 Poor score
70 32 36.0 −3.99 Poor score
72 33 32.0 1.00 Poor score
72 34 32.0 1.99 Poor score
74 34 38.0 −3.99 Poor score
74 34 36.0 −1.99 Poor score
74 34 39.0 −4.99 Poor score
74 35 32.0 2.99 Poor score
74 35 43.0 −8.00 Poor score
74 35 32.0 2.99 Poor score
74 35 36.0 −0.99 Poor score
74 35 35.9 −0.99 Poor score
74 35 36.0 −1.00 Poor score
74 35 47.0 −11.99 Poor score
74 35 32.0 2.99 Poor score
74 36 27.0 9.00 Good score
74 36 35.0 0.99 Good score
74 36 43.0 −6.99 Good score
74 36 32.0 4.00 Good score
74 36 34.0 2.00 Good score
74 36 53.0 −17.00 Good score
74 36 34.0 1.99 Good score
(Continued)

Phred Score Grouping—Predicted Exponential Smoothing Model
Forecast
Percentile Observed Phred Mean Fitted Phred Mean Residual Effect Decision
71 36 38.0 −1.99 Good score
75 36 34.0 1.99 Good score
79 36 35.0 0.99 Good score
82 38 35.0 3.00 Good score
82 38 32.0 5.99 Good score
87 38 32.0 5.99 Good score
93 39 35.0 3.99 Very good score
95 40 35.0 6.00 Very good score
across reads signifies good sequencing without artifacts or contaminants. Contaminating

sequences are identifiable by checking whether the frequency of a K-mer (a short sequence
of bases of length k) is unusually high relative to levels that would be predicted due to
chance (Khailany et al., 2009; Li, 2018). Sequences matching known adaptor sequences
should be trimmed before aligning the reads to a reference status, as mentioned in the
above table. The present results describe that the WGA quality score was assessed based
on the quintile and percentage. If the quality score falls on 80–99 percentile, that particular
score will be considered a better score for assessing the study intervention.
4.15 P yrosequencing
It is a method of DNA sequencing. The method is based on the principle in which the DNA
sequencing is determined by detecting the nucleotide incorporated by a DNA polymerase.
Pyrosequencing relies on light detection based on a chain reaction when phosphate is
released (Hwang et al., 2018; Kuhn et al., 2004; Katoh et al., 2017). It employs a series of four
enzymes to accurately detect nucleic acid sequences during the synthesis; the sequenc-
ing primer is hybridized to single-stranded biotin-labeled template DNA and mixed with
enzymes; DNA polymerase, ATP sulfurylase, luciferase and apyrase, and the substrate’s
adenosine 5’ cycles of four deoxynucleotide triphosphates (dNTPs) are separately added
to the reaction mixture iteratively. The cascade starts with a nucleic acid polymerization
reaction in which inorganic pyrophosphate (PPi) is released as a result of nucleotide incor-
poration by polymerase. Each nucleotide is incorporated by polymerase. The event is fol-
lowed by the release of PPi at equimolar levels for the amount of incorporated nucleotide.
Subsequently, the released PPi is quantitatively converted to ATP by ATP sulfurylase in
the presence of APS (Hoffmann et al., 2020; Hu et al., 2018; Hwang et al., 2018). The gener-
ated ATP derives luciferase-mediated conversion of luciferin to oxyluciferin, producing
visible light in amounts that are proportional to the amounts of ATPs. The light in the
luciferase-catalyzed reaction with a maximum of 560 nm wavelength is then detected by
a photon detection device, such as a charge-coupled device camera or a photomultiplier.
Apyrase is a nucleotide-degrading enzyme, which continuously degrades ATP and non-
incorporated dNTPs in the reaction mixture. There is certain time interval (usually 65
seconds) between each nucleotide dispensation to allow complete degradation. For this
FIGURE 4.28
Pyrosequencing technique.
reason, dNTPs addition is performed one at a time, because the sequences of template can
be determined by knowing the sequences of added nucleotides. The Schematic representa-
tion of pyrosequencing is presented in Figure 4.28.
(DNA)n + dXTP DNA Polymerase

 → (DNA)n+1 + PPi
−
PPi + APS ATP
Sufrulase
→ ATP + SO 24
ATP + Luciferin + Oxygen Luciferase

→ AMP + PPi + Oxyluciferin + CO 2 + Light
ATP + dXDP Apyrase

 → ADP + dXDP + 2Pi
ADP + dXDP Apyrase

 → AMP+dXMP+2Pi
4.16 Gene Sequencing Alignment

Pairwise DNA sequences: It is the very simplest method of sequencing alignment, and it
can be achieved by adding gaps (−) into sequences so that two sequences are aligned to
each other according to their homology (Harmer et al., 2002; Hashimoto et al., 2012). Two
bases aligned in the same column are thought to have a common ancestor. The pairwise
sequencing alignment can be carried out using a variety of computer programs based
on different algorithms and run parameters. It is, therefore, possible that different soft-
ware tools may produce different alignments, e.g., BLAST and FASTAq (Gene sequencing
alignment tool). The similarity of 16S rRNA gene sequences has widely been used in the
classification and identification of bacteria and archaea. For taxonomic purposes, we have
used the global alignment algorithm of Myer and Miller (1988). This method has been used
in the EzBioCloud service and the calculation of proposed similarity cutoff value of good
score 98.70% for bacterial species.
Gene sequencing alignment is represented in table form in Table 4.10.
Gap
A C G T G G A T - A C T
A C G - G A A T G A C T
 Match 
Similarity(%) =  × 100
 Match + Mismatch 
 9 
From the above:  × 100 = 90.0%
 9 + 1 
4.17 A lignment Parameters

Matches, mismatches, and gaps assessed the point mutation, and multiple sequencing was
studied by SNPs through phylogenetic tree. The distance was calculated based on the fol-
lowing formula:
≠ Mismatches
Distance N d =
≠ Mismatches+ ≠ Matches
Distance Ld =≠ Mismatches+ ≠ Matches+ ≠ Gaps
Nd = normalized distance and Ld = Larenstein distance (Used to determine the distance of

gene sequencing).
If Nd has a high value, it is nothing but dissimilarity in the sequences.
The scoring weight: for match: +m; for mismatch: s; and for gap: d.
Alignment score F = ( ≠ Matches ) * m − ( ≠ Mismatches ) * s − ( ≠ gap ) * d
4.18 COVID Sequencing

#Algorithm: Global alignment; #Length of sequence 1: 1333 nt; #Length of sequence 2: 1464
nt; #Similarity: 957/1330 (71.95%); #Number of mismatches:
373.ntFJ366809:GATGAACGCTGGCGGCGCGCCTAACACATGCAAGTCGAACGGCACC
CCTCTCCGGAGGGAAG---------
CGAGTGGCGAACGGCTGAGTAACACGTGGAAAACCTGCCCCCTCCCCCGGGA
CCGCCCGA A AGGACGGGTA ATACCGGATACCCCGGGGCGCCGCATGGCA
CCCCGGCTAAAGCCCCGACGGGAGGGGATGGCTCCGCGGCCCATCAGGTAGA
CGGCGGGGTGACGGCCCACCGTGCCGACAACGGGTAGCCGGGTTGAGAGACC
GACCGGCCAGATTGGGACTGAGACACGGCCCATACTCCTACGGGAGGCAGC
AGTGGGGA ATCT TGCACA ATGGGGGGA ACCCTGACGCAGCGACGCCGCG
TG CG G GACG GAG G CC T TCG G GTCGTA A ACCG C T T TCATCAG G GA- - - - - - - - - -
AGAGTCAA--------------
GACTGTACCTGCAAAAAAAGCCCCGGCTAACTACGTCCCAGCAGCCGCGATA
ATACGTAGGGGGCGAGCGTTATCCAGATTCATTGGGTATAAAGCGCGCGTAGG
CGGCCCGACATGCCGGGGGTAGAAGCGGGGGTCTCAACCCCCCGAAGCCCCC
GGAACCTTCGCGGCTTGGGTCCGGTAGGGGAGGGTGGAACACCCGGTGTAGCG
GTGGAATGCGCAGATATGGAGTGGCACCCCGGTGGCGAAGGCGGCCCTGTGG
GCCGAGACCGACGGTGAGGCGCGAAAGCTGGGGGAGAGAACAGGCTTAGAT
ACCGTGGTTGTCCCAGCCGAAGACGATTGGCGGTAGGTG--TGGGGGGACGA
TCCCCCCGCGCCGCAGCCAACGCATTAAGCGTCCCGCCTGGGGAGTACGGCC
GCAAGGATAAAAATCAAAGGAATGGACGGGGGCCCGCACAAGCAGCGGAGC
ATGTGGCTTAATTGGAAGCAGCGGGACGAACCTTACCAGGGCTTGACAT--AT
GGGTGAAGCGGGGGGGGCCCCGCCGCCGAGAGGAGCC--CATACAGGTGGTG
CATGGCTGTCGTCAGCTCGTGTCGTGAGATGTTGGGTTAAGTCCCGCAACGAG
CGCAACCCCCGCCGCGTGTTGCCATCGGGTGATGCCGGGAACCCACGCGGGA
CCGCCGCCGTCGAGGCGGAGGAGGGCGGGGAGGACGTCAAGTCATCATGCCC
CTTATGCCCTGGGCTGCACACGTGCTACAATGGCCGGTACAGAGGGATGCCA
CCCCG CGAG G G G GAG CG GATCCCG GA A AG CCG G CCCCAGT TCG GAT TG G
G G G C TG C A ACCCG CCCCC ACGA AGTCG GAGT TG C TAGTA ATCG
CG GATC AG C ATG CCG CG GTGA ATGAGATCCCG G G CC T TG C AC A
-----------------------------------------------------------------------------------------------
C ELV010 0 0 010:AT TGA ACG C TG G CG G CAG G CC TA ACACATG CA AGTCGA A
CGGTAACAGGAAGCAGCTTGCTGTTTCGCTGACGAGTGGCGGACGGGTGAGT
AATGTCTGGGAAA-CTGCCTGATGGAGGGGGATAACTACTGGAAACGGTAGCT
AATACCGCATAACGTCGCAAGAC-CAAAGAGGGGGACCTTCGGGCCTCTTGCC
ATCGGATGTGCCCAGATGGGATTAGCTAGTAGGTGGGGTAACGGCTCACCTAGGCG
ACGATCCCTAGCTGGTCTGAGAGGATGACCAGCCACACTGGAACTGAGACACGGTC
CAGACTCCTACGGGAGGCAGCAGTGGGGAATATTGCACAATGGGCGCAAGCCTGAT
GCAGCCATGCCGCGTGTATGAAGAAGGCCTTCGGGTTGTAAAGTACTTTCAGCGGG
GAGGAAGGGAGTAAAGTTAATACCTTTGCTCATTGACGTTACCCGCAGAAGAAGCA
CCGGCTAACTCCGTGCCAGCAGCCGCGGTAATACGGAGGGTGCAAGCGTTAATCG
G A AT TAC T G G G C G TA A AG C G C AC G C AG G C G G T T T G T TA AG T C AG AT G T
GAAATCCCCGGGCTCAACCTGGGAACTGCATCTGATACTGGCAAGCTTGAGTCTCG
TAGAGGGGGGTAGAATTCCAGGTGTAGCGGTGAAATGCGTAGAGATCTGGAGGAAT
ACCGGTGGCGAAGGCGGCCCCCTGGACGAAGACTGACGCTCAGGTGCGAAAGCGT
GGGGAGCAAACAGGATTAGATACCCTGGTAGTCCACGCTGTAAACGATGTCGACTT
GGAGGTTGTGCCCTTGAGGTGTGGCTTCCGGAGCTAACGCGTTAAGTCGACCGCCT
GGGGAGTACGGCCGCAAGGTTAAAACTCAAATGAATTGACGGGGGCCCGCACAAG
CGGTGGAGCATGTGGTTTAATTCGATGCAACGCGAAGAACCTTACCTGGTCTTGACA
TCCACGGAAGTTTTCAGAGATGAGAATGTGCCTTCGGGAACCGTGAGACAGGTGCT
GCATGGCTGTCGTCAGCTCGTGTTGTGAAATGTTGGGTTAAGTCCCGCAACGAGCG
CAACCCTTATCCTTTGTTGCCAGC-GGTCCGGCCGGGAACTCAAAGGAGACTGCC
AGTGATAAACTGGAGGAAGGTGGGGATGACGTCAAGTCATCATGGCCCTTACGACC
AGGGCTACACACGTGCTACAATGGCGCATACAAAGAGAAGCGACCTCGCGAGAGC
AAGCGGACCTCATAAAGTGCGTCGTAGTCCGGATTGGAGTCTGCAACTCGACTCCAT
GAAGTCGGAATCGCTAGTAATCGTGGATCAGAATGCCACGGTGAATACGTTCCCGG
GCCTTGTACACACCGCCCGTCACACCATGGGAGTGGGTTGCAAAAGAAGTAGGTAG
CTTAACCTTCGGGAGGGCGCTTACCACTTTGTGATTCATGACTGGGGTG
4.19 Gene Alignment and Its Applications

Gene alignment is a scientific way of arranging the sequences of DNA and RNA and pro-
teins. By alignment tools, we can identify the structural, evolutionary relation between
the gene sequences (Hamming et al., 2004). According to the alignment principles, if two
sequences in an alignment share a common ancestor, mismatches can be interpreted as a
point of mutation. In sequence alignments of nucleotide, the degree of similarity between
a nucleotide occupying a particular position in the sequences can be interpreted as a rough
measure of how conserved a particular region is among the lineages. The alignment was
carried out by the following techniques:
i. Global alignment
ii. Scoring matrices
iii. Local alignment
iv. Alignment with affine gap penalties.
4.19.1 Global Alignment

An alignment of two sequences is represented by three lines. The first line will show
the first sequence, and the third line shows the second sequence (Dallavilla et al., 2020;
Deng et al., 2020; Diao et al., 2020; Dumas et al., 2020; Habib et al., 2018). However, the
second line has a row of symbols. The symbol is a vertical bar whenever the characters
in two sequences match, and it is a space whenever they do not. Dots may be inserted in
either sequence to represent gaps (insertion). A general global alignment technique is the
Needleman–Wunsch algorithm, which is based on the dynamic programming. A local
alignment will be more beneficial for the identification of dissimilar sequences that are
suspected to include a region of similarity or similar sequences.
• Informal: A comparison of two potentially related sequences.

• Usually, alignment was done manually.
• Example: C T C T A G C A T T A G
• GTGCACCCA
• It is more prone to error identification, and it was applied for large sequences—
not systematic nor quantitative.
• Formal: Some scientific methods are applied for sequencing and alignment. It is
more precise and robust for the identification of errors or any other dissimilarities
between sequences.
• Precise operators for alignment: matching and gaps.
• Example: C T C T A G C A T T A G
• G T - G C A C C C A (insert a gap for better match)
• The following method(s) is/are employed to know whether there is any dis-
joint or insertion or variation among the gene sequences: (i) quantitative
scoring system for matches and gaps, (ii) systematic search among possible
alignments, (iii) use of alignment algorithms to find optimal alignment, and
(iv) different alignment algorithms (global, local, and affine-penalty).
TABLE 4.11
Scoring Metrics of Gene Sequencing
a b c d e
a 2 −1 1 −2 −5
b −1 3 −2 −2 −3
c 2 −2 5 −1 −1
d −2 −2 −1 3 −1
e −5 −3 −1 1 2
TABLE 4.12
Alignment of Scoring Metrics
a c d b d e d b e
a d c b d e d b e
• Input: Treat the two sequences potentially equivalent.

• Goal: Identify conserved regions and differences.
• Algorithm: Needleman–Wunsch dynamic programming.
• Applications:
• Comparing two genes with the same function (in human vs. mouse).
• Comparing two proteins with similar functions.
4.19.2 Scoring Matrices

The scoring matrices are used to identify the relative score made by matching of two char-
acters in a sequence alignment, e.g., Homo sapiens and chimpanzees. These are usually
log odds of the likelihood of two characters being derived from a common ancestral char-
acter (Tables 4.11 and 4.12).
Rewards = +18; penalties = −3.
The scoring matrix and alignment for a five-character alphabet: A scoring matrix (left)
stores the score for all possible character combinations. Rewards are positive numbers, and
penalties are negative numbers. Two strings in this alphabet are shown at right with verti-
cal lines indicating locations of agreement. Using the scoring matrix, the net score is +15.
4.20 W hole Genomic Analysis (WGA)

The whole genomic data sets on different annotations were simulated using the R sta-
tistical software; the Euclidean distance was employed to know the relative distance of
genes in different countries. Table 4.13 depicts that the genetic sequencing on the distance
for different annotations results in the understanding of how the disease mechanism
shoots the epidemic and endemic stages (pandemism). This result relies on the interpreta-
tions of the global endemism and equilibrium stages in different seasons. Primarily, the
TABLE 4.13
150
Correlation Matrix of Distance of Whole Genomic Sequences of COVID-19 with Different Annotations
India The The The South The
Annotation BLR Wuhan-Hu-1 USA USA USA France Egypt Egypt China China France Korea USA Israel
NC045512 0.00
Wuhan-Hu-1
MW566244 15.83 15.83
USA
MW562722_2_ 15.83 15.83 0.00
USA
MT671817 USA 15.69 15.69 8.31 8.31
MT470142 0.00 0.00 15.83 15.83 15.69
France
MW467502 0.00 0.00 15.85 15.85 15.67 0.00
Egypt
MW467494 0.00 0.00 15.83 15.83 15.69 0.00 0.00
Egypt
MW011767 0.00 0.00 15.81 15.81 15.67 0.00 0.00 0.00
China
MW011766 0.00 0.00 15.81 15.81 15.67 0.00 0.00 0.00 0.00
China
MT470137 0.00 0.00 15.83 15.83 15.69 0.00 0.00 0.00 0.00 0.00
France
MW466795 15.82 15.82 15.68 15.68 15.89 15.82 15.80 15.82 15.80 15.80 15.82
South Korea
MT438728 USA 15.84 15.84 15.70 15.70 15.83 15.84 15.82 15.84 15.82 15.82 15.84 0.00
MW672630 0.00 0.00 15.85 15.85 15.71 0.00 0.00 0.00 0.00 0.00 0.00 15.84 15.86
Israel
MT358641 0.00 0.00 15.83 15.83 15.69 0.00 0.00 0.00 0.00 0.00 0.00 15.82 15.84 0.00
Germany
MW674827 0.00 0.00 15.83 15.83 15.69 0.00 0.00 0.00 0.00 0.00 0.00 15.82 15.84 0.00
Israel
(Continued)
India The The The South The
Annotation BLR Wuhan-Hu-1 USA USA USA France Egypt Egypt China China France Korea USA Israel
MT926410 10.48 10.48 13.89 13.89 17.17 10.47 10.49 10.47 10.49 10.49 10.48 19.76 19.77 10.47
Wuhan_China
COVID-19 Gene Sequencing
MT466071 0.00 0.00 15.83 15.83 15.69 0.00 0.00 0.00 0.00 0.00 0.00 15.82 15.84 0.00
Uruguay
MT449639 USA 0.00 0.00 15.83 15.83 15.69 0.00 0.00 0.00 0.00 0.00 0.00 15.82 15.84 0.00
MT415321 India 0.00 0.00 15.83 15.83 15.69 0.00 0.00 0.00 0.00 0.00 0.00 15.82 15.84 0.00
MT371050 0.00 0.00 15.85 15.85 15.67 0.00 0.00 0.00 0.00 0.00 0.00 15.80 15.82 0.00
Sri_Lanka
MW674850 0.00 0.00 15.83 15.83 15.64 0.00 0.00 0.00 0.00 0.00 0.00 15.82 15.84 0.00
Israel
MW674815 0.00 0.00 15.83 15.83 15.69 0.00 0.00 0.00 0.00 0.00 0.00 15.82 15.84 0.00
Israel
MW366724 0.00 0.00 15.83 15.83 15.69 0.00 0.00 0.00 0.00 0.00 0.00 15.82 15.84 0.00
Tunisia
MT956917 0.00 0.00 15.83 15.83 15.69 0.00 0.00 0.00 0.00 0.00 0.00 15.82 15.84 0.00
Spain
MT019532 0.00 0.00 15.98 15.98 15.82 0.00 0.00 0.00 0.00 0.00 0.00 15.93 15.98 0.00
China
MW466791 15.82 15.82 15.68 15.68 15.85 15.82 15.80 15.82 15.80 15.80 15.82 0.00 0.00 15.84
South Korea
MW421988 0.00 0.00 15.81 15.81 15.69 0.00 0.00 0.00 0.00 0.00 0.00 15.80 15.82 0.00
Pakistan
MW421993 0.00 0.00 15.87 15.87 .69 0.00 0.00 0.00 0.00 0.00 0.00 15.80 15.82 0.00
Pakistan
151
analysis was done in the mid-season of the first wave of COVID pandemic (Chai et al., 2020;
Channappanavar et al., 2014; Chen et al., 2020). A total 28 annotations were used for compar-
ing the genetic distance. The results found that the USA and South Korea virus strains were
significantly correlated (p = 0.002). The global pandemic spread rapidly over the different
seasons affecting the population irrespective of seasons. Trend and seasonality were seen
in both countries. However, many studies opined that virulence and pandemic are directly
proportional to the seasonality. The virus can take any kind of deviation in a vulnerable
population, and many genetic variants were propagated due to the seasonal effect of the
disease (Cui et al., 2019). On a pragmatic approach, we have seen that in Indian population,
a total of five mutant gene variants were documented and seasonally affected the human
population. In the middle of March 2021, the UK mutant viruses or variants caused a very
big transmission or rapidly squared the disease spread (B.1.1.7 UK variants). The surge of
B.1.1.7 strains increases the infectivity by >75% (Cai et al., 2020). This advantage, Wenseleers
believes, is fueling the massive outbreak in India, on top of other contributing factors such
as recent gathering, election campaigns, rallies, and ritual conferences held in the month
of February–April 2021. The inclusion of deviation of health policy taken from citizen of
India and policy makers for relaxing the policy implementation like precautionary mea-
sures. Then, in the middle of February 2021 and early March 2021, the situation quickly
shifted and the virus surged explosively. Now, India is battling a horrific second wave of
COVID-19, reporting about 4 lakh cases and more than 3,500 deaths per day as reported by
the Ministry of Health and Family Welfare, Government of India (MoHFW, GOI) and the
Indian Council of Medical Research (ICMR). At the same time, the new variant that emerged
in India, known as B.1.617, began to dominate the outbreaks in several Indian states (more
so in Karnataka, Maharashtra, Delhi, UP, Kerala, and Tamil Nadu). This variant has more
than a dozen mutations, of which several are known to enhance transmissibility and help
the virus evade the immune system. Other variants are also circulating in India, including
B.1.351 from South Africa and B.1.1.7 from the UK (Fang et al., 2020). We figure out which
variant is spreading fast. Wenseleers used a statistical model to estimate how quickly cases
of each variant are rising in several regions. As per the official report of the USA, B.1.617
and the double mutant is a bit of a misnomer because it actually carries 13 mutations, 7 of
which are in the spike protein, but the moniker comes from two notable mutations found
in other variants that appeared together for the first time in this new strain—the L452R
mutation and the E484Q mutation. The L452R mutation in the spike protein was first found
in the COVID-19 variant detected in California. A study on California variant carrying this
mutation showed that it is 20% more transmissible than wild-type strains (Forster et al.,
2020; Fan et al., 2020; Gardy et al., 2018). The E484Q mutation is notable because it appears to
be very similar to the E484K mutation found in B.1.351 and P.1 Brazilian variant. The E484K
mutation in these variants is considered as an escape mutation, because it enables SARS-
Cov-2 to evade immune protection against monoclonal antibodies, which may decrease the
effectiveness of vaccines. The exact significance of these mutations is still being worked out.
Just because there are two worrisome mutations on one variant, they don’t necessarily need
to be more contagious or deadly (Groves et al., 2018; Gu et al. 2020). These two mutations are
worrisome, since the mutation makes the virus to gain more transmissibility and virulence.
WHO has declared B.1.617 a variant of interest instead of a variant of concern. WHO defines
a variant of interest as the one that has been found to cause community transmission and
has been found in multiple COVID-19 cases or clusters or has been found in multiple coun-
tries (Graham and Baric, 2010; Horta et al., 2020; Hoffmann et al., 2020a). In contrast, a vari-
ant of concern is defined as the one that has been associated with or has demonstrated
increased transmissibility, increased virulence, a change in clinical disease, or decreased
effectiveness of efforts to control or treat the inpatients (Table 4.14).
TABLE 4.14
Wuhan, The Sri South
Annotation Germany Israel China Uruguay USA India Lanka Israel Israel Tunisia Spain China Korea Pakistan Pakistan
MW674827 0.00
Israel
MT926410 10.47 10.48
Wuhan_
China
COVID-19 Gene Sequencing
MT466071 0.00 0.00 10.47

Uruguay
MT449639 0.00 0.00 10.47 0.00
USA
MT415321 0.00 0.00 10.47 0.00 0.00
India
MT371050 0.00 0.00 10.49 0.00 0.00 0.00
Sri Lanka
MW674850 0.00 0.00 10.49 0.00 0.00 0.00 0.00
Israel
MW674815 0.00 0.00 10.48 0.00 0.00 0.00 0.00 0.00
Israel
MW366724 0.00 0.00 10.47 0.00 0.00 0.00 0.00 0.00 0.00
Tunisia
MT956917 0.00 0.00 10.47 0.00 0.00 0.00 0.00 0.00 0.00 0.00
Spain
MT019532 0.00 0.00 10.47 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00
China
MW466791 15.82 15.82 19.78 15.82 15.82 15.82 15.80 15.82 15.82 15.82 15.82 15.96
South Korea
MW421988 0.00 0.00 10.47 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 15.80
Pakistan
MW421993 0.00 0.00 10.47 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 15.80 0.00 0.00
Pakistan
153
Table 4.15 depicts that the maximum density of gene mutation was modeled by different
kernel values. The highest value was recorded in the Gaussian normalcy model. It is vul-
nerable and more susceptible in the population: One infected person absolutely spreads
the disease to 28 uninfected persons at a time. The rapid disease pandemic was seen in
the USA population; a similar kernel was estimated for the relative comparison of genetic
sequences with epigenetic parameters. All the kernel values show significant results as
compared to the Gaussian model, and the marginal differences were less. Figure 4.29
describes the variability of kernel values in US population.
Table 4.16 depicts that the maximum density of gene mutation was modeled by differ-
ent kernel values. The highest value was recorded in the Gaussian normalcy model. It is
vulnerable and more susceptible in the population: Approximately one infected person
absolutely spreads the disease to 15 uninfected persons at a time. The low interaction
or augmentation of disease pandemic was seen in the South Korea population. A simi-
lar kernel was estimated for the relative comparison of genetic sequences with epigenetic
parameters. All the kernel values show insignificant results as compared to the Gaussian
model, and there are no marginal differences observed in the simulation figure. Figure
4.30 describes the variability of kernel values in the South Korean population. The expres-
sion of kernel value is very less, and the mobility of the disease spread is very less as com-
pared to the epicentric zone (zone surrounded more than > 60% positivity rate) of the USA,
India, the UK, Brazil, etc.
TABLE 4.15
Maximum Density Values of US Whole Genomic Sequences
of COVID-19
Kernel Max. Density
Gaussian 28.07
Epanechnikov 24.94
Rectangular 25.36
Triangular 27.94
Biweight 25.76
Cosine 26.11
Optcosine 25.21
FIGURE 4.29
Gene comparison among different species.
TABLE 4.16
Maximum Density Values of South Korea Whole Genomic Sequences
of COVID-19
Maximum Density Values of South Korea
Kernel x-Value Max. Density
Gaussian 15.82 0.69
Epanechnikov 15.82 0.58
Rectangular 15.29 0.50
Triangular 15.82 0.70
Biweight 15.82 0.62
Cosine 15.82 0.63
Optcosine 15.82 0.59
4.21 D iscussion
In the realistic approach, the increased importance of whole genomic sequences for clini-
cal and epidemiological investigations will support the existing pandemic situation to
explore the variants of viruses at global level. The scale of measurement was done based
on subjective and theoretical postulates to know the genomic response of COVID-19 from
different statistical perspectives (Khan et al., 2018). As per the WHO report during SARS
epidemic, only three virus genomes were publicly shared in the first month following
the identification of coronavirus as the causative pathogen, and only 31 were available
within 3 months. Genomic analysis was done through mathematical and statistical mod-
eling; it will be used to design vaccine trails, molecular assay, prevention strategies for
the control of disease, etc. The driven model would establish an association between the
disease and the new coronavirus concerned, but it was not sufficiently developed to allow
virus epidemiology to be studied in real time on a large scale. In contrast to microstud-
ies of whole genomic analysis, statistical intervention will be consistently used to know
the variation between different annotations and the polygenetic relation between whole
genomes. Many studies were focused on contrasting the metagenomics sequencing to
identify the causative pathogen of unexplained pneumonia within a week of disease being
reported. As per the literature, the pathogen was announced as a novel coronavirus in the
FIGURE 4.30
Gaussian Kernel density of WGS of South Korea with different regions.
beginning of January 2020; only six genomes were shared publicly before mid-January
2021, allowing the rapid development of diagnostic assays and strategies for extensive
virus genomic sequencing. Sequencing efforts have continued as the virus has spread
across the world; NCBI virtually maintained different COVID genomic sequencing anno-
tations in a separate database. A total of 28 sequencing annotations were expressed in
the genomic variation worldwide. Frequently, genomes have been generated within days
of case identification and used to understand the virus spread during the pandemic.
Statistical modeling for genomic analyses is capable of estimating the aspects of epide-
miological dynamics of viral disease that are new research findings correlated between
surges COVID 19 study intervention with respect to whole genomic sequencing at the
population level, because findings will allow insight mechanism into periods of an out-
break when cases were unobserved, powerful insights, which can be achieved even with
relatively sparse or massive genomic massive data throughput (Sanchez-Pacheco et al.,
2020; Shekhar et al., 2013; Skwark et al., 2017; Wu et al., 2020). Many important applications
of virus genomics in informing public health responses have been built on phylogenetic
or phylodynamic analyses (Avise and Wollenberg, 1997). Phylogenetics is used in almost
every branch of biology to investigate the evolutionary relationships between different
organisms using their genetic sequences. Phylogenetic trees study done by Shekhar et al.
(2013, Figure 1) are useful visualizations of such relationships. The branching patterns
and the length of the branches can be used to represent the evolutionary relatedness. One
of the limitations of the study is that not demonstrating an epistatic interaction means
that loss of fitness by a mutation at one locus is enhanced (positive epistasis) or com-
pensated (sign epistasis) by a mutation at another locus. During the formulation of our
model, we consider a patrimonial model with varying degrees of state variables; epis-
tasis then points to the possibility of using human and pathogen interaction in closed
environments. Nevertheless, considering the number of combinations of potential epide-
miological factors to explore the target intervention for describing phylogenetic trees and
photodynamic (Cancer treatment) aspects, we applied various probability distribution
models to know the variability of disease intervention with respect to gene sequencing
and epidemiological considerations. Many statistical tools were demonstrated by using
real data sets of genome of COVID sequence (Al-Benna et al., 2020; Andersen et al., 2020).
Predictive approach was used to make good the genomic sequences omits to the mutual
dependencies in fitness of observed gene distance. Simultaneously, we noted that one
can also start looking for the interaction of different annotations in compliance with
the disease spread. Asper the gene sequencing findings, the USA and South Korea are
found to be highly augmented for spreading of diseases rapidly at worldwide. The mod-
els were clearly focused on discovering and uncovering the fundamental genetic pat-
terns of nCov19 due to the viral genetic instability. Our efforts were focused on exploring
the views of statistical perspectives of SARS-Cov-2 migration and evolution in different
geographical locations and can be helpful to fight against the pandemic at global level.
The findings of the present study provide useful insights into SARS-Cov-2 replication,
pathogenicity, and analytical implications. We look forward to explore the new results
with other relative studies, e.g., phylogenetic interactions of whole genomic sequencing in
different countries (Figures 4.31 and 4.32).
FIGURE 4.31
Gaussian kernel density of whole genomic sequences of the USA.
FIGURE 4.32
Gaussian kernel density of WGS in different regions of South Korea.
4.22 Conclusions
This chapter concludes that the whole genomic analysis is a primary tool used for taking
clinical, epidemiological decisions at the right time. It describes various statistical model
approaches to genomic analysis. The essence of the demonstrated models would be more
beneficial for epidemiologists, research beginners, postdoctoral degree fellows, and sci-
entists for the inception of new infectious micro- and macrostudies using a pragmatic
approach and will also provide support for exploring new postulates of virology- and
bioinformatics-related studies at population level.
References
Al-Benna S. Association of high level gene expression of ACE2 in adipose tissue with Mortality
of Covid-19 infection in obese patients. Obes Med 2020; 19: 1–4. doi: 10.1016/j.obmed.
2020.100283.
Andersen K.G., Rambaut A., Lipkin W.I., Holmes E.C., Garry R.F. The proximal origin of SARS-
CoV-2. Nat Med 2020; 26: 450–452.
Avise J.C., Wollenberg K. Phylogenetics and the origin of species. Proc Natl Acad Sci USA 1997; 94:
7748–7755. doi: 10.1073/pnas.94.15.7748.
Cai H.Y., Cai K.K., Li J. Identification of novel missense mutations in a large number of recent SARS-
CoV-2 Genome Sequences, 28 April 2020. doi:10.20944/preprints202004.0482.v1.
Chai X., Hu L., Zhang Y., Han W., Lu Z., Ke A., et al. Specific ACE2 expression in cholangio-
cytes may cause liver damage after 2019-nCoV infection. BioRxiv 2020. doi: 10.1101/
2020.02.03.931766.
Channappanavar R., Fett C., Zhao J., Meyerholz D.K., Perlman S. Virus-specific memory CD8 T cells
provide substantial protection from lethal severe acute respiratory syndrome coronavirus
infection. J Viro 2014; 88: 11034–11044. doi: 10.1128/JVI.01505-14.
Chen N., Zhou M., Dong X., Qu J., Gong F., Han Y., et al. Epidemiological and clinical characteristics
of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet
2020; 395: 507–513. doi: 10.1016/S0140-6736(20)30211-7.
Cui J., Li F., Shi Z.L. Origin and evolution of pathogenic coronaviruses. Nat Rev Microbiol 2019; 17:
181–192. doi: 10.1038/s41579-018-0118-9.
Dallavilla T., Bertelli M., Morresi A., Bushati V., Stuppia L., Beccari T., et al. Bioinformatic analy-
sis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses. Eur Rev Med
Pharmacol Sci 2020; 24: 4558–4564.
Deng X., Gu W., Federman S., Du Plessis L., Pybus O., Faria N. A genomic survey of SARS-CoV-2
reveals multiple introductions into Northern California without a predominant lineage.
medRxiv 2020. doi: 10.1101/2020.03.27.20044925.
Diao B., Wang C., Tan Y., Chen X., Liu Y., Ning L., et al. Reduction and functional exhaustion of T
cells in patients with coronavirus disease 2019 (Covid-19). Front Immunol 2020; 11(827): 1–7. doi:
10.3389/fimmu.2020.00827.
Dumas A., Bernard L., Poquet Y., Lugo-Villarino G., Neyrolles O. The role of the lung microbiota
and the Gut-Lung axis in respiratory infectious diseases. J Cell Microbiol 2018; 20: 12966. doi:
10.1111/cmi.12966.
Fan C., Li K., Ding Y., Lu W.L., Wang J. ACE2 expression in kidney and testis may cause kidney and
testis damage after 2019-nCoV infection. medRxiv 2020. doi: 10.1101/2020.02.12.20022418.
Fang B., Liu L., Yu X., Li X., Ye G., Xu J., et al. Genome-wide data inferring the evolution and pop-
ulation demography of the novel pneumonia coronavirus (SARS-CoV-2). BioRxiv 2020. doi:
10.1101/2020.03.04.976662.
Forster P., Forster L., Renfrew C., Forster M. Phylogenetic network analysis of SARS-CoV-2 genomes.
Proc Natl Acad Sci USA 2020; 117: 9241–9243. doi: 10.1073/pnas.2004999117.
Gardy J.L., Loman N.J. Towards a genomics-informed, real-time, global pathogen surveillance sys-
tem. Nat Rev Genet 2018; 19: 9–20. doi: 10.1038/nrg.2017.88.
Graham R.L., Baric R.S., Recombination, reservoirs, and the modular spike: Mechanisms of corona-
virus cross-species transmission. J Virol 2010; 84: 3134–3146.
Groves H.T., Cuthbertson L., James P., Moffatt M.F., Cox M.J., Tregoning J.S. Respiratory disease fol-
lowing Viral lung infection alters the Murine Gut Microbiota. Front Immunol 2018; 9: 182. doi:
10.3389/fimmu.2018.00182.
Gu S., Chen Y., Wu Z., Chen Y., Gao H., Lv L., et al. Alterations of the Gut Microbiota in Patients with
Covid-19 or H1N1 influenza. Clin Infect Dis 2020. doi: 10.1093/cid/ciaa709.
Habib S., Siddiqui A.H., Azam M., Siddiqui F., Chalhoub M. Actinomyces viscosus causing dis-
seminated disease in a patient on methotrexate. Respir Med Case Rep 2018; 25: 158–160. doi:
10.1016/j.rmcr.2018.08.009.
Hamming I., Timens W., Bulthuis M.L., Lely A.T., Navis G., van Goor H. Tissue distribution of ACE2
protein, the functional receptor for SARS coronavirus. A first step in understanding SARS
Pathogenesis. J Pathol 2004; 203: 631–637. doi: 10.1002/path.1570.
Harmer D., Gilbert M., Borman R., Clark K.L. Quantitative mRNA expression profiling of ACE 2, a
novel homologue of angiotensin converting enzyme. FEBS Lett 2002; 532: 107–110. doi: 10.1016/
s0014-5793(02)03640-2.
Hashimoto T., Perlot T., Rehman A., Trichereau J., Ishiguro H., Paolino M., et al. ACE2 links amino
acid malnutrition to microbial ecology and intestinal inflammation. Nature 2012; 487: 477–481.
doi: 10.1038/nature11228.
Hoffmann M, Kleine-Weber H, Schroeder S, Kruger N, Herrler T, Erichsen S et al. SARS-CoV-2 cell
entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor.
Cell 2020a; 181: 271–280. doi: 10.1016/j.cell.2020.02.052.
Hoffmann M., KleineWeber H., Pohlmann S. A multibasic cleavage site in the spike protein of SARS-
CoV-2 is essential for infection of human lung cells. Mol Cell 2020b; 78(4): 779–784.
Horta E.R., Weigt M., Phylogenetic correlations have limited effect on coevolution-based contact
prediction in proteins. BioRxiv 2020. doi: 10.1101/2020.08.12.247577.
Hu D., Zhu C., Ai L., He T., Wang Y., Ye F., et al. Genomic characterization and infectivity of a novel
SARS-like coronavirus in Chinese Bats. Emerg Microbes Infect 2018; 7: 154–158. doi: 10.1038/
s41426-018-0155-5.
Hwang B., Lee J.H., Bang D. Single-cell RNA sequencing technologies and bioinformatics pipelines.
Exp Mol Med 2018; 50: 96. doi: 10.1038/s12276-018-0071-8.
Katoh K., Rozewicki K., Yamada K.D. MAFFT online service: Multiple sequence alignment, interac-
tive sequence choice and visualization. Briefings Bioinform 2017; 20: 1160–1166.
Khailany R.A., Safdar M., Ozaslan M. Genomic characterization of a novel SARS-CoV-2. Gene Rep
2020; 19: 100682.
Khan T.A., Nanjundan G., Basavarajaiah D.M., Azharuddin M. Statistical model derivation
and extension of hardy Weinberg equilibrium. Int J Curr Microbiol App Sci 2018; 7(10):
2402–2409.
Kuhn J.H., Li W., Choe H., Farzan M. Angiotensin-converting enzyme 2: A functional receptor for
SARS coronavirus. Cell Mol Life Sci 2004; 61: 2738–2743. doi: 10.1007/s00018-004-4242-5.
Li H. Minimap2: Pairwise alignment for nucleotide sequences. Bioinformatics 2018; 34(18):
3094–3100.
Li Y.C., Bai W.Z., Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in
the respiratory failure of Covid-19 patients. J Med Virol 2020; 92: 552–555. doi: 10.1002/
jmv.25728.
Liao M., Liu Y., Yuan J., Wen Y., Xu G., Zhao J., et al. The landscape of lung Bronchoalveolar
immune cells in Covid-19 revealed by single-cell RNA sequencing. medRxiv 2020. doi:
10.1101/2020.02.23.20026690.
Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., et al. Genomic characterisation and epidemiology of
2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020; 395:
565–574. doi: 10.1016/s0140-6736(20)30251-8.
MacLean O.A., Orton R.J., Singer J.B., Robertson D.L., No evidence for distinct types in the evolution
of SARS-CoV-2. Virus Evol 2020; 6: 34.
Mann J.K., et al. The fitness landscape of HIV-1 Gag: Advanced modeling approaches and validation
of model predictions by in vitro testing. PLoS Comput Biol 2014; 10:1003776.
Mercatelli D., Giorgi F.M., Geographic and genomic distribution of SARS-CoV-2 mutations. Front
Microbiol 2020; 11: 1800–1805.
Neher R.A., Shraiman B.I., Statistical genetics and evolution of quantitative traits. Rev Mod Phys 2011;
83: 1283–1300.
Phelan J., et al. Controlling the SARS-CoV-2 outbreak, insights from large scale whole genome
sequences generated across the world. BioRxiv, 29 April 2020. doi: 10.1101/2020.04.28.
066977.
Rad A.H., McLellan A.D., et al. Implications of SARS-CoV-2 mutations for genomic RNA structure
and host microRNA targeting. BioRxiv, 16 May 2020. doi:10.1101/2020.05.15.098947.
Rockett R.J., Arnott A., Lam C., Sadsad R., Timms V., Gray K.-A., et al. Revealing Covid-19 trans-
mission by SARS-CoV-2 genome sequencing and agent based modelling. BioRxiv 2020. doi:
10.1101/2020.04.19.048751.
Sanchez-Pacheco S.J., et al. Median-joining network analysis of SARS-CoV-2 genomes is neither
Phylogenetic nor evolutionary. Proc Natl Acad Sci USA 2020; 117(23): 12518–12519.
Shekhar K., et al. Spin models inferred from patient-derived viral sequence data faithfully describe
HIV fitness landscapes. Phys Rev 2013; 88: 062705.
Skwark M.J., et al. Interacting networks of resistance, virulence and core machinery genes identified
by genome-wide epistasis analysis. PLoS Genet 2017; 13: 1006508.
Wu F., et al. A new coronavirus associated with human respiratory disease in China. Nature 2020;
579: 265–269.
5
Real-Time PCR (RT-PCR) for COVID-19
Diagnosis and Changes in Threshold Cycle (Ct)
in Association with Different Parameters
5.1 Introduction
Real-time reverse transcriptase PCR continues to be the gold standard test for the diag-
nosis of COVID-19, HIV, and many other infectious diseases (Attia et al., 2021). A pos-
itive reaction is detected by the accumulation of florescent signals (Chen et al., 2020b).
For the diagnosis of infectious diseases, the classical detection methods such as culture
and immunoassays have been replaced by or supplemented with RT-PCR (real-time poly-
merase chain reaction). As per the literature, by direct detection of DNA or RNA of the
pathogen, RT-PCR allows us to detect the disease status and facilitates early intervention.
Being a highly specific diagnostic test, it allows for a fast and elite treatment option or
regimen of the individual subject or patient; thereafter, the DNA isolation and target gene
fragments are specifically amplified (amplicons) and, if present, detected with florescent
hydrolysis probe. The florescence signal increases with the load of amplified DNA, which
is detected by the unit of RT-PCR mechanism of diagnosis (Dhama et al., 2020; WHO; CDC
nCov19 report, 2020). RT-PCR diagnostic procedure encompassed with molecular in vitro
diagnostic tests aids in the detection and diagnosis of SARS-Cov-2 infections based on the
widely used advanced nucleic acid amplification techniques. The oligonucleotide primer
and dual-labeled hydrolysis probes (TaqMan®) and controls are used in RT-PCR for the
in vitro qualitative detection of nCov19 in respiratory specimens (Chen et al., 2020a). The
oligonucleotide primers and probes for the detection of disease status are selected from
the regions of virus nucleocapsid “n” gene. The technique is designed for specific detec-
tion of SARS-Cov-2 (two primer/probe sets) in control samples, and clinical specimens are
also included in the present technique or process (De Mesa Herrera et al., 2021). RNA was
isolated and purified from upper and lower respiratory specimens, which is reverse tran-
scribed to cDNA and subsequently amplified in the Applied Biosystems 7500 Fast Dx Real-
Time PCR Instrument (Figure 5.1). In the process, the probe anneals to a specific target
sequence located between the forward and reverse primers. During the extension phase of
the PCR cycle, the 5’ nuclease activity of Taq polymerase degrades the probe, causing the
reporter dye to separate from quencher dye, generating a fluorescent signal (De Alwis et
al., 2020). With each cycle, additional reporter dye molecules are cleaved from their respec-
tive probes, increasing the fluorescence intensity. The fluorescence intensity is monitored
at each PCR cycle. Many laboratory COVID reports show cycle threshold (Ct) values from
RT-PCR tests. A lower Ct value indicates that the patient has a higher VL: Patients with a
DOI: 10.1201/9781003204794-5 163

FIGURE 5.1
Flow chart of Rt PCR diagnostic test for COVID-19.
Ct value from 17 to <24 have a high VL and those with a Ct value in the range of 24 to <31
should be isolated or hospitalized. A study in China showed that probably only 10% of
population with high RNA VL are responsible for the spread of 80% of the infection. A
lower Ct value, 29 or below, is a sign of high VL; 30–37 indicates moderate amount of VL;
and 38–40 indicates minimal VL (General Office of National Health Committee, 2019). As
per the Indian Council of Medical Research (ICMR), there are no reliable studies that prove
a definitive direct correlation between the Ct value and infectiousness or severity of the
disease, and also it does not change the course of treatment or disease management (Guan
et al., 2020). The Ct value may differ depending on the test kit used or the testing machine.
In the indistinct level of RT-PCR, many analytical research interventions would be neces-
sary for generating separate mathematical algorithms for the accurate detection of viral
plasma load with respect to various epidemiological, clinical, and age-related attributes.
Scientifically, the RT-PCR mechanism is directly augmented with various epidemiologi-
cal attributes, e.g., PCR cycle, and Ct values (threshold) will depend on age-specific traits;
for example, for younger age population without any comorbid condition, the number of
cycles taken for transition output of disease status is very less compared to older age group
associated with one or more comorbid conditions. The detection of VL RNA not only aids
in the diagnosis of illness, assessing the duration of illness and providing the palliative
care to cases, but also provides epidemiological and surveillance information. Further, the
Ct value differs from one diagnostic kit to another. The comparability of Ct values among
different kits is a challenge as vetted laboratories across the country (India) are using a
mixed type of cases. The patient in early symptomatic stage may show a high Ct value,
which may subsequently change (Huang et al., 2020). In such cases, the high Ct value will
give a false sense of security. The severity of the disease progression depends on the spe-
cific host factors besides viral load (RNA plasma VL) may suffer from sever disease illness
due to triggering of the immunological and virological suppression patients (HIV /Cancer
etc) (Lu et al., 2020). To fill this scientific research gap, mathematical and epidemiological
modeling is very important to form true hypotheses, on a new practical research approach
(Lucas et al., 2020). The present study formulates new modeling techniques for the extrapo-
lation of significant variations in the number of cycles associated with plasma RNA viral
load based on the age-specific and various epidemiological factors of COVID-19 subjects
(Figure 5.2).
RT-PCR Ct Value and Diagnosis of COVID-19 165
FIGURE 5.2
Changes of Ct values in younger population.
5.2 A High Threshold Value of Ct in COVID-19

The high value of Ct is due to many underlining factors: (i) asymptotic infectivity risk
where the stage of infection is not known, (ii) presymptomatic infection that subsequently
may develop into symptomatic infection with high RNA plasma VL, and (iii) during
acute infection with a high risk of infectivity, if the samples collected are insufficient or
degraded samples (suboptimal sample storage and handling techniques). However, a
symptomatic person should be assumed to be potentially infectious within the first 10
days of the onset of disease and an asymptomatic person for 10 days after positive swab
results. During the convalescent phase of COVID-19 when the RNA plasma VL is dimin-
ished, the persistence in detecting viral genetic material has been observed for SARS-
Cov-2. Immunocompromised and hospitalized individuals with a critical illness are more
likely to shed potentially infectious viruses for longer. While high Ct values may be associ-
ated with a high RNA plasma VL and reduced infectivity, a swab taken at a single point
in time does not provide details about the trajectory or subsequent illness course (Machhi
et al., 2020; Pan et al., 2020b). Some asymptomatic cases of SARS-Cov-2 RT-PCR have reported
Ct values comparable to symptomatic patients. Another study reported earlier in May 2020
stated a reduction in Ct values in asymptomatic cases compared to symptomatic cases. Ct
values in some patients were similar to those in presymptomatic and symptomatic phases.
More importantly, in infected persons suffering from terminal illness and ambulatory
conditions (HIV–TB coinfection, malignancy, etc.), the RNA plasma VL consistently shows
a higher value (elevated) besides various treatments and immunological and clinical con-
ditions of the patients.
The RT-PCR laboratory data sets were collected from various tertiary care hospitals (wet
laboratories). The epidemiological traits, viz. age, gender, mode of transmission (from
travel), comorbidity, duration of treatment of comorbid cases, preclinical existing cases,
onset of infection, travel history, history of other viral diseases, family cluster type of fam-
ily, history of social movement, prevention strategies (regular use of mask), and other vital
demographic parameters, were collected using pretested and structured questionnaires.
Collected data were carefully scrutinized. If the data show skewness, necessary data trans-
formation was done with the highest epoch by using separate software. The components
of RT-PCR data sets shown in Table 5.1 were included.
The observed values of RNA plasma VL (Y1,Y2…Yn) and the number of PCR cycles
(X1,X2,X3 …Xn) were considered as the dependent and independent variables of life data
sets of diagnostic test of RT-PCR (Table 5.2). The known variables were iterated at time “t”
by the substitution of Ct value in bootstrap method. Gaussianity (normalcy) was assumed
( )
for formulating model Yij = N µ , σ 2 . The model was generalized based on different epide-
miological, clinical, and demographical attributes.
( )
n
Yt = ae bxi (5.1)
where a = point of inflection of Ct value—the control threshold value, “Y” is the RNA
plasma viral load (copies per ml) at time “t”, the exponential value “e” = 2.71, b is the slope
of incremental changes of input variables of RNA plasma VL and the number of cycles,
Xi = age of the infected person from the ith comorbid condition, and n = the number of PCR
cycles generated inclusive of diagnostic procedure.
1
Yt = a + β 0 x0 + β1x1 + β 2 x2β n xn (5.2)
1+ e
1
Yt = (5.3)
1 + e α + β i xi
TABLE 5.1
Different Components and Their Description of RT-PCR SOP
Component Volume Quantity Description
SARS-Cov-2 reaction mix 1mL/vial One viral Reagent for amplification, probes, and primers
for virus target and internal reference
SARS-Cov-2 enzyme mix 80mL/vial One viral Taq polymerase, reverse transcriptase, and
uracil DNA glycosylase (UDG)
SARS-Cov-2 positive 750mL/vial One viral Mixed solution of pseudo-virus with target
control virus genes and internal reference
SARS-Cov-2 no template 750 mL/vial One viral DNase-/RNase-free water
control
TABLE 5.2
Variables of Concern in Model Construction
Random State Random State
Variable Attributes Variable Attributes
X1 Age group X11 Social structure
X2 Gender—male coded as 1 and X12 Intervention of hygiene
female coded as 2
X3 Comorbidity (yes coded as 1; no X13 Agent pathogen
coded as 2) Toxicity, virulence, infectivity,
susceptibility to antibiotics, etc.
X4 Duration of treatment X14 Genetic susceptibility
X5 Prior exposure—yes 1; no 2 X15 Demographic vital parameters;
income
X6 Type of intervention X16 Nutritional status
Immunize; isolate
X7 Symptomatic coded as 1; X17 Family cluster
asymptomatic coded as 2
X8 Climatic condition X18 Status of family cluster immigrants
from foreign country
X9 Physical structure X19 Measures or strategies used for the
control of disease
X10 Population density in affected X20 Policy-making decision
area
X21 Clinical attributes
Consider a complex mode with more than one predictor, X1,X2, X3…Xn. The Cox propor-
tional hazards model is
h ( t ) = h0 ( t ) exp (α i + β 0 x0 + β1x1 + β 2 x2 … β n xn ) (5.4)
Suppose we wish to compare two participants in terms of their expected hazards and the
first has X1 = a and the second X1 = b. The expected hazard h(t) is equal to h0(t) exp (b1a) and
h(t) = h0(t) exp (b1b). The hazard ratio of these two expected hazards is h0 (t) exp (b1a)/h0 (t)
exp (b1b) = exp (b1 (a−b)), which does not depend on time “t”. Thus, the hazard is directly pro-
portional to different time.
 h(t) 
 h (t)  = exp (α i + β 0 x0 + β1x1 + β 2 x2 … β n xn ) (5.5)
 0 
Sometimes, the model is expressed differently, relating the relative hazard, which is the
ratio of the hazard at time t to the baseline hazard, to the risk factors.
 h (t ) 
ln   = exp (α i + β 0 x0 + β1x1 + β 2 x2 … β n xn ) (5.6)
 h0 ( t ) 
In equation (1.10), we can take the natural logarithm (ln) on each side of the Cox propor-
tional hazards regression model, to produce the following which relates the log of the
relative hazard to a linear function of the predictors. Notice that the right-hand side of the
equation looks like the more familiar linear combination of the predictors or risk factors
(as seen in the multiple linear regression model).
 h(t) 
From equation (1.11), we have assumed that f (t) =  
 h0 (t) 
f (t) = a ( 1 + β n )
t
(5.7)
a = the initial value of Ct and βn is the rate of change of growth of Ct with respect to nth
cycle.
α > 0 and β n > 0 and growth takes place at time “t”
f ( t ) = P, P0 − initial stage
( )
t
Pn = P0 * e 1+ β0x0 + β1x1 + β2 x2…βnxn) (5.8)
( )
t
Pn = Pn−1 * e 1+ β0x0 + β1x1 + β2 x2…βnxn) P0
P0 is the initial stage of RNA plasma VL, which changes at nth cycle.
( )
t
Pn = Pn−1 * e 1+ r
P −P 
r = e  n n− 1  (5.9)
 Pn−1 
a
yt ~ From equation (3.1), we simulate equation (5.10).
1 + be t ,X1
Younger COVID population RT-PCR RNA Ct value 10:9.8 cycle target points: R2 = 0.981,
e = exponential plot, a = 0.988, log RNA VL b = 1.56 × 1017, t = −10.58.
a
yt ~
1 + be t ,X1
5.4 Model Output
Chi-square = 3.6089; df = 1; P = 0.0575.
Coefficients, standard errors, odds ratios, and 95% confidence limits.
Variable Coeff. StdErr P OR low–high
1 0.1236 0.0973 0.2039 1.1316 0.9351 1.3693
Intercept: 9.0694 7.1707 0.2059
As per the literature survey, the diagnosis of new virus use RT-PCR tests to identify the
point mutation in many clinical samples. The CDC developed a protocol for RT-PCR that
includes specific primers designed to bind to key areas of COVID-19. The current situa-
tion exemplifies the challenges of how to best utilize testing during outbreaks of novel
pathogens. The present criterion is too narrow to identify the accurate epidemiological
cause and effect besides the monitoring and control of the spread of disease. In this para-
digm, we demonstrated new algorithm models using different variants of epidemiology.
TABLE 5.3
Predicted Probability Outcomes of the Survival Rate of COVID
Patients with Different Age Groups Correlated with the Ct Value of
Real-Time PCR
X-Mean Age Group Y Probability CI 95%
33 Years 0 0.006 [0.000–0.944]
36 Years 0 0.009 [0.000–0.933]
63 Years 0 0.213 [0.022–0.767]
64 Years 0 0.239 [0.029–0.763]
65 Years 1 0.263 [0.039–0.759]
76 Years 0 0.580 [0.218–0.873]
77 Years 1 0.610 [0.228–0.893]
78 Years 0 0.639 [0.233–0.911]
79 Years 1 0.667 [0.236–0.928]
83 Years 1 0.776 [0.230–0.973]
However, we have not given high priorities for testing patients with serious complications,
unexplained respiratory illness, contacts of known cases, etc., In March 2020, numerous
cases of COVID-19 had exhibited mild nonspecific symptoms of COVID-19 and also we
called for testing in accordance with the SOP of WHO. As we noticed during the study
period, most of the cases were suffering from one or more comorbidities and also they are
taking treatment or therapy for diseases at least 6–10 years (IQR 3–10 years) (organ trans-
plantation patients and patients with life-threatening diseases are highly vulnerable to
COVID-19). During the RT-PCR testing interval time, laboratory experts will not consider
the epidemiological parameters to render the Ct value for the confirmation of COVID. In
this propensity, the driven threshold value of Ct will vary among individuals. Currently,
so many tested laboratories did not consider the epidemiological parameters such as age,
family cluster, duration of infection, method of selection of samples, and geographical pro-
file of patients. A related concern is the misunderstanding of resultant COVID algorithms
of threshold value of RT-PCR. Given the disease incubation period (estimated as 2–14 days
or 24 days), a negative result does not rule out the infection, particularly for people with
a known exposure. A positive result in an otherwise well or mildly ill patients does not
require urgent medical attention, but does require isolation at this time. Accurate com-
munication will be essential to avoid the overlapping confusion with respect to healthcare
specialists and infected or uninfected persons. The mean Ct value of all 150 samples was
35.65 (IQR 27.55–37.18). A total of 33% cases were classified as non-severe (asymptotic to
the x-axis; normalcy) (Table 5.1). Many cases were found to be symptomatic with mild to
moderate symptoms (75.0%); the rest of the cases (20%) had a severe illness requiring life
support treatment. The results found that there is no significant difference between Ct
value (p > 0.01) with respect to the younger population (Table 4.1; p > 0.01). Those who not
contacted infection of COVID had a mean Ct value of 21.36 (IQR 19.81–21.22); 35% cases
expressed fewer symptoms, but not to be confirmed as COVID (Ct value is less than the
threshold level). Such cases were referred isolation, home quarantine, etc. Fifteen percent-
age of cases expressed indifference in Ct value (median Ct). This population was consid-
ered negative, and they can be referred to further observations. As per the model findings,
it was observed that there is a strong correlation between the threshold value (Ct) and the
age-specific incidence of COVID (p < 0.01; odds 8.36) with respect to demographic charac-
teristics of the patients. Further, travel history (traveled from abroad), BMI>30 kg/mm3,
high economy, and urban population are seen to have higher Ct values as compared to rural
population. The relative measure of Ct value is more augmented due to the higher inci-
dence of COVID in urban population with secondary contact of one or more persons (the
threshold value expressed was more than the reference range with a standard deviation of
1.76 (CI 95%; 32.36–38.11)). The above findings were highly correlated with travel history,
lack of social distancing, ignorance of the policy interventions, and lack of awareness of
spreading of virus (p < 0.0034; odds 4.54; Hz 0.36–1.34). The age-specific Ct value was mod-
eled in equation (5.10). The selected factors were demonstrated by the real data of Ct values
in association with age specificity of COVID-19 and gender-matched frequency. The model
results determined that the age groups of 45–59 years, 62–70 years, and >70 years had
higher Ct values (the mean Ct value was 38.13 with a standard deviation of 1.16; the mean
number of cycles was 23.44). An estimated odds ratio of patients traveled from abroad (the
UK, the USA, Italy, Brazil, and some European countries) had expressed elevated Ct values
irrespective of the age group and gender. The proportion of asymptomatic cases were
expressed similar expression of the symptoms besides with travel history, except the mean
age of patients ranged 70–80 years shows more likely to be infected as compared with
other age groups (the maximum likelihood estimation was 123.22; odds 10.36; p = 0.06).
These findings were extrapolated or simulated from the binary logistic regression model.
This demonstrated model propagated accurate results and showed more epochs for propa-
gating transient probabilities irrespective of the age and gender of the population. Males
had high Ct values as compared to females (the mean Ct value of males was 37.13; odds 1.22;
p < 0.01). Figure 5.3 clearly demonstrates that the duration of symptoms correlated with
FIGURE 5.3
Changes of Ct values in asymptomatic population.
>28 days 21.16%
Day 22−28 25.44%

Day 0−7
Day 15−21 30.18% Day 8−14
Day 15−21
Day 8−14 70.34 % Day 22−28
>28 days
Day 0−7 95%
0 20 40 60 80 100
Percentage
FIGURE 5.4
Percent prevalence of infectivity from the disease inception to 28 days.
positivity rate of disease. The positivity rate was higher in days 0–7 (95%), followed by 8–14
days (70.34%); 15–21 days (30.18%); 22–28 days (25.44%); and > 28 days (21.16%) (Figure 5.4).
5.5 Discussion
Numerous studies have opined that the lowering of Ct threshold parameter may lead to
missing several infectious persons. Due to the paucity of literature and increasing data
sets, we shall not correlate the exact mechanism of variability of Ct values in mixed popu-
lation considering age, specific duration of illness, travel history, and demographic charac-
teristics (Qin et al., 2020; Shi et al., 2020). Lowering Ct parameter may lead to transmission
patentability (potentiality) and these techniques has been adopted to decide the cutoff
values in RT-PCR. Globally, the accepted cutoff value for COVID ranges between 35 and 40,
depending on instructions from the respective manufacturer of the testing equipment. In
Indian context, the ICMR has arrived at a Ct value of 35 based on clinical laboratory expe-
rience and inputs taken from several virology laboratories. As per the previous research
findings, many factors are important for interpreting an RT-PCR test, and the results may
also depend on the method of specimen collection and duration of infection to collec-
tion and to analysis. Again, Ct values differ between nasal and oropharyngeal specimens
collected from the same individual and patients’ travel history (immigrants from high
prevalence countries). Besides, epidemiological parameters, temperature of transporta-
tion, and time taken from collection to receipt in the laboratory can also adversely impact
Ct values. The Ct value clearly envisages the absolute VL in the body system. However,
the Ct value is inversely correlated with VL. It does not have any bearing on the severity
of the disease. Many studies describe that patients can have a low Ct value, which means
VL is high enough to be detected rapidly, but patients may still be asymptomatic. Fewer
number of cycle can be reached threshold, Ct value that emerges during RT-PCR tests,
the gold standard for detection of the COVID. In an RT-PCR test, RNA is extracted from
the swab specimen collected from the suspected person (Sun et al., 2020; Upadhyay et al.,
2021). It is then converted into DNA, which is then amplified. Amplification refers to the
process of creating multiple copies of the genetic material (in this case, DNA). This pro-
cess will improve the ability of the test to detect the presence of virus or variants of the
virus. The amplification takes place through a series of number of cycles: One RNA copy
becomes two, two become four, and so on, and after multiple cycles, a detectable amount
of virus is produced. The RT-PCR plateau values as a measure of RNA plasma VL (cop-
ies per ml) showed that the level of novel virus RNA in the upper respiratory tract was
greatest around symptoms onset, which steadily declined during the first 8 days (IQR
4–9 days) after illness onset and then plateaued. In the mean duration of symptoms, i.e., 6
days, onset of likelihood Ct value was obtained from the model was 30 (CI 95% 28–32). The
elderly population, especially organ transplantation patients and patients who were tak-
ing treatment for one or more comorbidities (mean of treatment was 10.54 years), showed a
significant Ct of 38.22 (statistically insignificant difference was seen in other populations).
Further, the model was formulated with demographic characteristics in correlation with
the Ct value. The urban population was shown to have elevated Ct values compared to
rural population (p < 0.001). There is a significant difference in Ct values after 8 days of
symptoms irrespective of age and demographic characteristics of the population (Wang et
al., 2020; WHO, 2020 report). The impact of demographic factors on the dynamic profile of
COVID-19 has not been studied before through construction of statistical modeling (Wang
et al., 2020). Previous studies clearly suggested that novel coronavirus is more likely to
infect older individuals with weaker immune functions (ICS). Our demonstrated model
describes the key findings of RT-PCR Ct values and the positivity relation between the
elderly population and patients having one or more comorbidities. The results show that
demographic factors such as older age and urban population had a significantly shorter
time interval of positivity (Wishaupt et al., 2017; Xie et al., 2020; Yang et al., 2020; Zhonghua
Liu et al., 2020). One of the possible explanations is that the dysfunction of immune system
in older and immunocompromised patients resulted in a prolonged elimination of the
virus. Male patients had a slightly short time interval (mean 10.12 days), and females had
a longer time interval (mean 12.16 days) of infection. Risk factors such as alcohol, smoking,
and drug abuse history may relate to the above findings. In the present study, so many
pitfalls and several limitations were taken into consideration (Zhao et al., 2020). First, in
this model setting, we consider selected variables of patrimonial behavior (state variables
were not considered). Second, this study only investigated the impact of Ct value on demo-
graphic characteristics such as age and gender, while other epidemiological factors were
not included for the construction of model (Table 5.3).
5.6 Conclusions
The summary of the results concludes that the Ct value differs significantly in elderly and
comorbid patients. The demographic profile includes predisposing factors, and it is neces-
sary to substitute the RT-PCR test to derive the Ct value accurately. The present demon-
strated model is more robust and reliable for the estimation of Ct values in association with
age and other laboratory vital parameters. It will be highly convergent in propagating the
Ct values and lowering the number of cycles in the elderly population.
References
Attia Y.A., El-Saadony M.T., Swelum A.A., Qattan S.Y.A., et al. Covid-19: Pathogenesis advances in
treatment and vaccine development and environmental impact an updated review. Environ Sci
Pollut Res 2021; 28: 22241–22264.
Chen G., Wu D., Guo W., Cao Y., et al. Clinical and immunological features of severe and moderate
corona virus disease 2019. J Clin Investig 2020a; 130: 2620–2629.
Chen N., Zhou M., Dong M. Epidemiological and clinical characteristics of 99 cases of 2019 novel
corona virus pneumonia in Wuhan, China: A descriptive study. Lancet 2020b; 36(20): 30211–7.
De Alwis R., Chen S., Gan E.S., et al. Impact of immune enhancement on Covid-19 polyclonal hyper-
immune globulin therapy and vaccine development. E BioMed 2020; 55: 102768.
De Mesa Herrera L.R. Immuno-informatics approach in designing SARS-CoV-2 vaccine from experi-
mentally determined SARS- CoV T-cell epitopes. J Appl Pharm Sci 2021; 11: 29–36.
Dhama K., Patel S.K., Pathak M., Yatoo M.I., Tiwari R., Malik Y.S., et al. An update on SARS-CoV-2
Covid-19 with particular reference to its clinical pathology, pathogenesis, immunopathology
and mitigation strategies. Travel Med Infect Dis 2020; 37: 102–106.
General Office of National Health Committee. Notice on the issuance of a program for the diagnosis
and treatment of novel coronavirus (2019-nCoV) infected pneumonia (trial revised fifth edi-
tion) 2019.
Guan W., Ni Z., Hu Y., Liang W., Ou C., He J. et al., Clinical characteristics of coronavirus disease 2019
in China. N Engl J Med 2020; 382: 1708–1720. doi: 10.1056/NEJMoa2002032.
Huang C., Wang Y., Li X. et al., Clinical features of patients infected with 2019 novel Coronavirus in
Wuhan, China. Lancet 2020; 395(10223):497–506.
Lu H., Stratton C.W., Tang Y.W. Outbreak of pneumonia of unknown etiology in Wuhan, China: The
mystery and the miracle. J Med Virol 2020; 10(1):25678–79.
Lucas C., Wong P., Klein J., Castro T.B.R., et al. Longitudinal analyses reveal immunological misfiring
in severe Covid-19. Nature 2020; 584: 463–469.
Machhi J., Herskovitz J., Senan A.M., Dutta D., et al., The natural history pathobiology and clinical
manifestations of SARS-CoV-2 Infections. J Neuroimmune Pharmacol 2020; 15(1):359–386.
Pan F., Ye T., Sun P. Time course of lung changes on chest CT during recovery from 2019 novel
Coronavirus (Covid-19) Pneumonia. J Radiol 2020a; 13(1): 370–75.
Pan Y., Guan H., Zhou S. Initial CT findings and temporal Changes in Patients with the novel
Coronavirus pneumonia (2019-nCoV): A study of 63 patients in Wuhan, China. Eur Radiol
2020b; 2(13): 165–174.
Qin C., Zhou L., Hu Z., Zhang S., et al. Dysregulation of Immuneresponse in Patients with Coronavirus
2019 (Covid-19) in Wuhan, China. Clin Infect Dis 2020; 71: 762–768.
Shi H., Han X., Zheng C. Evolution of CT manifestations in a patient recovered from 2019 Novel
Coronavirus (2019-nCoV) pneumonia in Wuhan, China. Radiology 2020; 295: 20.
Sun B., Feng Y., Mo X., Zheng P., et al. Kinetics of SARS-CoV-2 Specific IgM and IgG responses in
Covid-19 patients. Emerg Microbes Infect 2020; 9: 940–948.
Upadhyay S.K., Dan S., Girdhar M., Rastogi K. Recent advancement in SARS-CoV-2 diagnosis treat-
ment and vaccine formulation: A new paradigm of nanotechnology in strategic combating of
Covid-19 pandemic. Curr Pharmacol Rep 2021; 7: 1–14.
Wang D., Hu B., Hu C. Clinical characteristics of 138 hospitalized patients with 2019 Novel
Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 2020; 10 (1):1585–87.
Wang X., Guo X., Xin Q., Pan Y., Hu Y., et al., Neutralizing antibody responses to severe acute respira-
tory syndrome coronavirus 2 in coronavirus disease 2019 inpatients and convalescent patients.
Clin Infect Dis 2020; 71: 2688–2694.
Wishaupt J.O., van der Ploeg T., Smeets L.C., de Groot R., Versteegh F.G.A., Hartwig N.G. Pitfalls in
interpretation of Ct-values of Rt-PCR in Children with Acute respiratory tract Infections. J Clin
Virol 2017; 90: 1–6.
Xie X., Zhong Z., Zhao W., Zheng C., Wang F., Liu J. Chest CT for typical 2019-nCoV Pneumonia:
relationship to negative RT-PCR testing. Radiology 2020; 12(1): 20–24.
Yang Y., Yang M., Shen C. Evaluating the accuracy of different respiratory specimens in the labora-
tory diagnosis and monitoring the viral shedding of 2019-nCoV infections. MedRxiv 2020; 17(1):
36–39.
Zhao Y., Qin L., Zhang P., Li K. Liang L. et al. Longitudinal Covid-19 profiling associates IL-1RA and
IL-10 with disease severity and RANTES with mild disease. JCI Insight 2020; 5: 1–2.
6
COVID-19 Vaccination Modeling
Approach to Public Health Policy
6.1 Introduction
COVID can cause very serious life-threatening health complications; presently, there are
many ways to curb the COVID 19 virus viz mass vaccination, wearing mask, less exposure
of crowded places etc. It affects the human population and their quality of life (QOL). If a
person gets infected and becomes sick, he can obviously spread the disease rapidly at the
rate of R0 = 1.5–3.0 reproduction number (global-level estimation). In this aspect of pan-
demic, many public health authorities and private organizations fight against the pandemic
by adopting different preventive strategies and exploring new health policies at the global
level. As per the literature, whole genomic analysis was done at the global level by using
different annotations of NCBI (open-source platform). Approximately 743 mutant genes
were identified worldwide, and yet we notice a large multiplication of mutant genes (point
mutation) in many regions. Our first priority of health policy is the eradication of virus
and control of pandemic by implementing various prevention strategies such as mass vac-
cination, social distancing, and wearing of masks. The spiraling infection rate and severe
economic crisis pushed many government organizations and private research groups to
explore the development of newer vaccines and vaccination strategies under the stipulated
guidelines of Emergency Use Authorization (EUA), approved by FDA. Many countries
already incepted vaccination at selected sample and population levels. New COVID vac-
cine trials show that they are safe and effective and display an inherent mechanism in
controlling this current pandemic. These new vaccines offer varied levels of protection by
inducing both antibody and T cell responses without any adverse vaccine reactions in sub-
jects with known innate immunity (Dushoff et al., 2007; Nuraini et al., 2020). As per the lit-
erature available, vaccinated individuals are less likely to be infected with overt symptoms
and potentially less likely to transmit the virus to others. The vaccination or immunization
will provide direct protection by reducing susceptible infection or disease; in other words,
vaccination provides direct protection by significantly limiting the number of people get-
ting infected in a population or to become infectious (Figure 6.1). Vaccination effects will
be assessed in clinical trials by measuring the efficacy to prevent infection/disease and
by reducing infectiousness, including the assessment of the indirect impacts of COVID
vaccine on the quality of life of an individual person. Scientifically, COVID vaccines have
a unique protective mechanism to fight against the virus on a broad perspective. Many
candidate vaccines, which initially look promising, are likely to fail during the testing pro-
cess. The process of developing new vaccines begins with identifying the so-called candi-
date vaccine. Thus, some candidate vaccines are being developed worldwide. On the basis
DOI: 10.1201/9781003204794-6 175

of strategy, we classify vaccines as follows: (i) viral vector vaccines, (ii) attenuated virus,
(iii) DNA vaccine, (iv) virus-like particles, (v) subunit viral protein, (vi) inactivated virus,
etc. (Table 6.1). The vaccines being developed include mRNA, vector, and virus-inactivated
vaccines. The mRNA vaccines (Pfizer, Covishield, and Sinopharm) are a new type that
instruct host cells to make harmless piece of what is called the spike protein (a spike protein
or peplomer protein is a protein that forms a large structure known as a spike). The spike
protein present on the surface of the virus facilitates the adsorption and attachment of the
virions to the host cell receptor ACE2, followed by entry and uncoating of the virus. COVID
mRNA upon entering the nucleus of the susceptible host instructs the cells to make the pro-
teins of viral interest. The new virions so synthesized would be presented on the cell sur-
face; the immune system spots the proteins and begins building an immune response by
making antibodies and virus-specific cytotoxic T cells to fight the infection. More research
is required for the intervention of COVID-19, through vaccination at micro- and macro-
levels (Anderson et al., 2020). On a relative basis, all vaccination trials aim to protect against
future infection. The above driving mechanism should be proved by computational statis-
tics and mathematical interventions to reach the end process of vaccine trials worldwide.
Eventually, on health emergency situation, such as spiraling COVID pandemic, reliable vac-
cination trials and real-life data sets are very crucial to scale up the public health programs
through statistical and mathematical interventions for taking good policy decisions, e.g.,
estimation of efficacy, selection of target population, interim analysis, and vaccine feedback
assessment. The statistical model is a very important tool for the researchers and policy-
makers for drafting a new health policy, besides unearthing COVID-19 variants that might
arise from vaccine trials by using advanced statistical and mathematical models (recursive
factors of COVID pandemic). In this proximity, we demonstrate different statistical models
and also discuss the selection criteria for target population (it will be incepted based on
cluster and stratification approach). It is a reasonable tool implementation or reckoning for
new health policy at individual or population level. The model-based approach will fulfill
FIGURE 6.1
Herd immunity with and without immunization.
COVID-19 Vaccination Modeling 177
TABLE 6.1
Different Types of Vaccines
Approach Work Process SARSCov-19 Vaccines Similar Vaccines
Inactivated or Use a form of the virus that has Sinopharm, Sinovac Cholera, polio,
attenuated virus been inactivated or weakened so MMR, yellow
that it does not cause disease, but fever, TBC
still generates immune response
Viral vector Use a virus that has been generally Gamaleya Research Institute Ebola
(non-replicating) engineered so that it can’t cause (Sputnik V), AstraZeneca and
disease, but can produce Oxford University, CanSino
coronavirus proteins to safely Biologics Inc., Johnson and
generate an immune≈response Johnson, Covishield
Protein subunit Use harmless fragments of proteins EpiVacCorona, Novavax Seasonal influenza,
that mimic the COVID-19 virus to HBV, tetanus
safely generate an immune
response
DNA Synthetic DNA fragment (plasmid) Inovio None (new tech)
that encodes a COVID-19 antigen
RNA Typically, an RNA segment of the Pfizer/BioNTech, Moderna, None (new tech)
viral genome that codes for the CureVac
virus spike protein (or other
antigenic regions) is prepared in a
suspension of lipid nanoparticles
the necessary prerequisites for inception of early and advanced scientific studies on vaccine
trials. Numerous models have already been developed and used to provide insights into
the transmission mechanisms and control of COVID-19. The present modeling technique
includes both theoretical and practical postulates of a large number of testing strategies;
unknown and high levels of uncertainties of pandemic call for the principles of predictive
computation models. Our demonstrated models will have a potential impact on policy-
making decisions with respect to widespread vaccination efforts. The output of the model
will be easily adapted to different vaccine trials to test the insight mechanism, by using the
statistical intervention and exploring a wide range of algorithms and vaccination coverage
in different situations.
6.2 What Else Does a Vaccine Contain?

Adjuvants enhance the immune response and reduce the dose of antigen needed, e.g., by
stimulating the body to produce more antibodies or by creating a longer-lasting immune
response.
Adjuvants enhance the immune response in the human body by giving SARS-CoV-2 vac-
cines (I or II dose). In the interest of immune reconstruction, we reduce the dose of antigens
and simultaneously stimulate our body to respond and produce more antibodies from the
metabolic process. In this process, our body creates a longer-lasting immune response. In
addition to that, during the process of a metabolic pathway, the lipid nanoparticles (NLPs)
multiply enormously after SARS-CoV-2 vaccination. (It is the most clinically advanced
non-viral gene delivery system.) In contrast to biological phenomena, the lipid nanopar-
ticles safely and effectively deliver nucleic acids to break the virus multiplicity chain (a
major barrier preventing the development and use of genetic medicines) develop immunity.
This barrier will protect the RNA and help to produce the desired proteins for an antigenic
response.
6.3 Model Formulation—Need for Model Formulation

Considering vaccine safety measures, the primary interest of the researchers is to
explore vaccination-efficient convergent models to know the overall effects of new vac-
cines. The statistical/mathematical model will provide sufficient information to test the
null hypothesis that the relative risk of an adverse event is attributable to the new vac-
cination of COVID-19. Many developed countries such as the USA, the UK, Spain, and
Russia are unable to control the pandemic at the early stage of infection. Despite many
people continuing to wear masks, maintaining social distance, and following COVID
appropriate behaviors as issued by the Government of India from time to time, in the
middle of the March–April 2021 spring season, all Indian states recorded infection rates
ranging from 6,000 to 36,000 (new cases). In most of the states, infection was uncontrol-
lable to the extent that even if millions of people had been vaccinated, million others
would still be infected and CFR would shoot up to >2.5; thus, many people became ill
and severely suffered from the deadly virus infection. According to the previous sta-
tistical models, the coming months are very critical to reduce new infections and death
toll. With the advancement of infectious disease science and emergency crisis, AUC
authorized to use different vaccines at the global level (vaccination matrix presented
in Table 6.1). Ultimately, there will be a larger number of people affected by the virus
as the pandemic is set to continue past the time of writing (March 2022). Even with the
current precautions, some areas of the country have let the pandemic rage so uncon-
trollably that it is too late for the vaccine to have a major impact. As a matter of fact,
definitely vaccination will help to eradicate the disease with deviations in normalcy;
mostly, the pandemic will burn out on its own (Figures 6.2 and 6.3).
FIGURE 6.2
Reasons of rejection of vaccination in population.
Swelling 7 27
Nausea 7 14
Chills 7 27
Joint pain 7 21
Fever 7 25
Muscle pain 17 42
Headache 26 42 Dose 1 Dose 2

Fatigue 29 50
Injection site pain 68 75
0 20 40 60 80 100 120 140 160
FIGURE 6.3
Different Complications experienced by the vaccinated population.
6.4 Methods
Statistical models have been used for solving the realistic problems of various vaccination
trials, and models have been used by researchers for many years to represent the various
aspects of process of drug formulation, distribution, and inception of vaccination at the
target population. However, the model applications will describe the effect of vaccination,
potency, and efficacy by real data sets of clinical trials. These formulated models mainly
focused on different mathematical and statistical new interventions, well adopted to
describe the dynamism of formulated models. All models were demonstrated by real data
of different COVID vaccines used at the global level. Further, we have built new theoretical
postulates for the advancement of COVID vaccination, vaccination coverage, and percent-
age of vaccination correlation with various demographic sketch of the respondents of vacci-
nations. Some of the vaccination data sets were downloaded from the COVID Worldometer,
an open-source and virtual platform. The primary and secondary real data sets were sche-
matically modeled and analytically compiled by R statistical software. Different modeling
methods like predictive, stochastic convergent, time series stochastic, and new state-varied
stochastic models were demonstrated by real-life data sets of vaccination at the global plat-
( )
form. Random variables x1 , x2 , x3 … xn ~ N σ 2 , µi = Ve. The vaccination effect was mod-
eled from the state variables of COVID clusters (the clusters were selected from the low,
medium, and high prevalence states or provinces) with age- and gender-specific predispos-
ing factors, primary infection, and symptomatic and asymptomatic population. The groups
symptomatic and asymptomatic were grouped into vaccinated and unvaccinated. Relevant
vaccinated population will be assessed for the inbuilt herd immunity based on the relapse
stage (assessed the cured patient for the period of 6 months). As per the SOP of WHO,
we considered non-relapsed cases in the period of 6 months as having herd immunity.
The flowchart of model is described as follows (Figure 6.4 and Table 6.2).
The vaccine effect and coverage can be calculated by the following statistical model:
n n
Ve = Tijk + ∑∑(S
i=1 j=1
ij )
+ ASij I = U I + H ijk + ∈ijk (6.1)
FIGURE 6.4
COVID-19 vaccines available at the global level and used construction of primary mathematical model.
TABLE 6.2
Significance Test ANOVA F-Table
F-Critical
Source of variation df SS MSS Calculated Value
Vaccine (v − 1) SSV MSV Fv = MSV/MSEa
Asymptomatic population (a) (a − 1) SSA MSA Fa = MSA/MSEa
Error a (v − 1(a − 1)) SSEA MSEa
Symptomatic (b) (b − 1) SSB MSB Fb = MSB/MSEb
Infected (c) (c − 1) SSC MSC Fc = MSC/MSEb
Uninfected (d) (d − 1) SSD MSD Fd = MSD/MSEb
Error b(c − 1) (d − 1) SSEB MSEb
Interaction
VxA (v − 1) (a − 1) SSVA MSVA Fva = MSVA/MSEi
VxB (v − 1) (b − 1) SSVB MSVB Fvb = MSVB/MSEi
VxC (v − 1) (c − 1) SSVC MSVC Fvc = MSVC/MSEi
VxD (v − 1) (c − 1) SSVD MSVD Fvd = MSVD/MSEi
AxBxCxD (a − 1)(b − 1)(c − 1) (d − 1) SSI MSI Finter = MSI/MSEi
Error (interaction) v(a − 1)(b − 1)(c − 1) (d − 1) SSEi MSEi
Total v(abck-1) SST
Fcalculated value ≥ Ftable error df reject H0.
where
Ve = vaccine effect (immunization);
Tijk = total primary infection at ith vaccine jth cluster kth respondent;
Sij = the number of symptomatic cases received at ith vaccine jth cluster;
ASij = the number of asymptomatic cases received at ith vaccine jth cluster;
I = the number of infections confirmed by RT-PCR; U j = the number of uninfected
atjth cluster;
Hijk = the number of persons who obtained herd immunity from ith vaccine on jth
cluster with selective kth respondents;
€ijk = errors associated with ith vaccine jth cluster kth respondent.
The National Expert Group on Vaccine Administration for COVID-19 (NEGVAC) in

its proceedings recommended that vaccines that have been granted Emergency Use
Authorization (EUA) by one of the regulators in the US, the UK, or Japan or those that have
been listed in the World Health Organization’s (WHO) emergency use lists may be granted
similar EUA in India. The Government of India accepted the exotic and indigenous vac-
cines listed in Table 6.3. Vaccines manufactured by three companies may be eligible for fast
track approval in India (Figure 6.5 and Table 6.4).
According to a published research paper by the CDC’s V-safe smartphone app, a higher
percentage of people reported side effects after receiving the second dose of Pfizer–
BioNTech vaccine than after receiving the first dose. Injection site pain was the most com-
mon, whereas nausea and chills were uncommon (Figure 6.6). The target population was
TABLE 6.3
Different Types of COVID-19 Vaccines Available at Global Level
Producer Name Type Storage temp (°C) Cost INR
Pfizer—BioNTech Tozinameran mRNA −70°C 1,431
Moderna MRNA1273 mRNA 2°C–8°C 2,348–2,715
Sinopharm BBIBP-CorV Inactivated 2°C–8°C <5,650
Sinovac Biotech CoronaVac Inactivated 2°C–8°C 1,027
Novavax NVX-Cov2373 Protein subunit 2°C–8°C <734
Gamaleya Center Sputnik V Viral vector 2°C–8°C 1,220
Johnson and Johnson JNJ-78436735 Viral vector 2°C–8°C <734
Serum Institute of India Covishield Viral vector 2°C–8°C 200 per dose
Bharat Biotech—ICMR Covaxin Inactivated 2°C–8°C 295 per dose
Source: Health Ministry, COVID guidelines report 2020.
Target population
Frontline healthcare workers
Respondents from essential service
Geriatric population ( > 60 years)
Children, last stage–general Population
Selection criteria
Age specific (Older aged)
BMI ( <20 Kg/m3; 20-30 kg/m3 and > 30 kgm3 )
(preference will be given to highest BMI)
Comorbidity– Organ transplantation,
Life-threatening diseases, and Immigrants
Geographical
High prevalence states or area–I preference
FIGURE 6.5
Flow chart for selection of target population for vaccination.
TABLE 6.4
Different Types of Vaccine and their Merits
Pfizer Moderna Johnson and Johnson
Approved for full use in at least five Approved for full use in Switzerland and Approved for emergency use
countries. Has an efficacy of 91.3%. for emergency use in several others. Has in various countries. Has an
Two doses 3 weeks apart is the an efficacy of 94.50%. Two doses4 weeks efficacy of 72% in the USA.
standard dosage recommended apart is the standard dosage Only a single dose is required
FIGURE 6.6
Side effects of COVID-19 vaccination.
selected for COVID-19 vaccination; however, the schedule of first vaccination will be allo-
cated for essential workers, which extend beyond frontline healthcare workers and essen-
tial services, which include workers in the food industry and domestic suppliers, police
and military staff who maintain public safety, and workers who maintain electricity, water,
fuel, information, and financial infrastructure (Figures 6.7 and 6.8). Certain selection cri-
teria of cases are appended in Table 6.2 would be considered on a priority basis. The sec-
ond vaccination scheme targets people who might experience irreversible and devastating
harm from COVID-19 (i.e., admission to hospital, admission to critical care, etc.). However,
another target population include people older than 65, those with high-risk health condi-
tions, and those in close contact with people at very high risk of poor outcomes (e.g., staff
in nursing homes and long-term care facilities). The vaccine experts considered people with
the following underlying conditions such as cardiovascular disease, CKI, chronic respira-
tory disease, chronic liver disease, diabetes, cancer with direct immunosuppression, can-
cer without direct immunosuppressants but with possible immunosuppression caused by
treatment, HIV or AIDS, TB (excluding latent infection), chronic neurological disorders,
and sickle cell disorders. The third possible vaccine allocation scheme focuses on reducing
SARS-Cov-2 transmission; in this phase, high transmission group should be selected or tar-
geted. Target population include adults and children involved in economic or educational
activities who experience high risk of economic or educational harm from not working
FIGURE 6.7
Cascade linkage model for the selection of target population for COVID-19 vaccine.
Indian Vaccine doses per 1000

Lakshadweep 1924
6152 Vaccine doses per 1000
Ladakh 6427
7131
Puducherry 10104
12565
Chandigarh 13748
16183
Mizoram 16868
23743
Meghalaya 24506
25435
Manipur 41926
93956
Himachal Pradesh 107197
136796
Uttarakhand 138550
165804
Jammu and Kashmir 207426
232295
Jharkhand 266015
311410
Miscellaneous 341572
361950
Telangana 368132
370846
Kerala 438113
503323
Odisha 533093
561857
MP 644583
655375
WB 689194
821059
Gujarat 883118
926466
UP 1152042
0 500000 1000000 1500000
FIGURE 6.8
Priority group for COVID-19 vaccines. (From Lao PDR, 2020.)
or going to educational institutions. These adults and children also have a higher prob-
ability of transmission when going back to work or school because of their large number
of contacts. To reduce symptomatic infections and to stop virus transmission, vaccination
should extend to all people younger than 60 years without any underlying conditions.
These people can further be reclassified into four groups (aged 18–44 years, aged >45 years,
aged 5–17 years, and aged 0–4 years) on the basis of their risk of transmitting the virus and
projected economic harm from not working when considering the adult groups.
6.5 Determination of Vaccination Effects by Statistical Tools or Methods

In a broad spectrum, vaccine efficacy is the numerical percentage of the reduction in dis-
ease in a vaccinated group of people compared to an unvaccinated group, using the most
favorable conditions. Vaccine efficacy was first designed by Greenwood and Yule in 1915
for the cholera and typhoid vaccines. Mathematically, efficacy is defined as the numerical
reduction in the chance you will get disease if vaccinated compared to not vaccinated. For
example, consider 100 people get the vaccine and another 100 get a placebo. Let’s say five
people in the vaccine group, i.e., 5%, get sick and 25 people in the placebo group, i.e., 25%,
get sick (Table 6.5).
Efficacy = 1 − (0.05/0.025) = 0.80 = 80.0%.
Efficacy = (q control-q vaccination/q control) * 100.
 b a 
 (b + e ) − ( a + d )  ARU − ARV 
VE =   * 100 = VE =   * 100 (6.2)
 b   ARU
 (b + e ) 
6.6 Herd Immunity
Nesha Sharma et al. (2021) defined herd immunity as the resistance group for attack by a dis-
ease of the immunity of a large proportion of the members and the consequent lessening of
the likelihood of an affected individual coming into contact with a susceptible individual.
In other words, the prevalence of immunity in a population due to which it becomes difficult
for the organism to circulate and reach a new susceptible individual is called herd immunity.
It is well known that not everyone in a population needs to be immunized to eliminate the
disease. We classify herd imunity into two types, viz. (i) innate (inherent) herd immunity:
TABLE 6.5
Vaccination Status 2 × 2 Contingency Table for VE Calculation
Clinical status Vaccinated Unvaccinated Unknown
Symptomatic a b c
Asymptomatic d e f
It is due to genetically determined physiological changes with respect to antibody produc-

tion or other defense mechanisms in a herd. It does not depend on the previous exposure of
herd with infection, and it may arise in a herd through prolonged exposure to an infection
or natural selection. For example, some population of domestic fowl have innate resistance
to pullorum disease due to an inherited difference in lymphocyte numbers immediately
after hatching. Sergeev and Khachatryan (2019), Moore et al. (2021), and Saad Roy et al.
(2020) reported that the inheritance of resistance to influenza virus in mice is probably due
to a single dominant autosomal allele Verelst et al. (2016) and Zhou et al. (2020) showed
that resistance to brucellosis in swine may be genetically determined. (ii) Acquired herd
immunity: It is a type of herd immunity where a sufficient number of its members have
actually been exposed naturally or artificially to infectious agents during their lifespan.
This kind of exposure may be made very early in life; e.g., polio in paralytic form are rare
in countries with poor hygiene and sanitation where exposure to the virus occurs in early
part of life, but in countries where the hygiene is better and exposure is delayed until school
age, the paralytic manifestations are higher. The important limitation of herd immunity
was noticed; generally, HI only applies to diseases that are contagious. It does not apply
to diseases such as tetanus, foodborne botulism, and intoxications. It might be associated
with the emergence of variants of pathogens more dangerous than the existent one due to
evolution pressure on the pathogen or selection pressure on the antigen variant and may
lead to antigenic variation among pathogens at a much faster rate than it would have been
in the absence of herd immunity, leading to serotype replacement.
Mathematically, we define herd immunity as the impact of the fractions immune in the
community on the per capita rate of transmission of an infectious agent. The level of herd
immunity can be measured in reference to the magnitude of reduction in the value of R0.
The relation of herd immunity can be measured by the magnitudinal differences in the
reproduction number, if the reproduction number is more, herd immunity show less asso-
ciation. We assessed the herd immunity by the following methods:
i. Cross-sectional and longitudinal serological survey

ii. Serum and saliva (viral infection)
iii. Activated T cells (bacteria and protozoa)
iv. Quantitative assays.
The disease rate has been determined based on average reproduction number in other
word it is a measure of potential for transmission of diseases (reproductive number R0); the
basic reproductive number is the mean number of individual directly infected an infec-
tious case through the total infectious period, when introduced to a susceptible population
(discussed in Chapter 1).
R0 = p * c * d (6.3)
where
p = probability of transmission per contact;
c = contact per unit time; d = duration of infectiousness.
Infection will disappear if R0 < 1.
It becomes endemic if R0 = 1.
It becomes endemic if R0 > 1.
The minimum proportion (p) of population that needs to be immunized in order to obtain
herd immunity is
 1 
p > 1− (6.4)
 R0 
If R0 = 3 , immunity threshold = 67%.

If R0 = 16 , immunity threshold = 94%.
If R0 is the mean number of secondary cases in a susceptible population, then R is the
mean number of secondary cases in a population where a proportion “p” are immune.
R = R0 − ( p * R0 ) (6.5)
If R0 is 2, the R < 1 if the proportion of immune, p, is >0.05.

If R0 is 4, the R < 1 if the proportion of immune, p, is >0.75.
The higher the R0, the higher the proportion of immune required for herd immunity.
Imperfect vaccination was calculated by the following equation:
 1  L
1 − R  1 + V 
0  
pc >  (6.6)
 R0 v 
ε 1 −
 R0 
where pc is the critical fraction of each cohort immunized, R0 is the reproductive number
for unvaccinated, R0 v is the reproductive number for vaccinated, L is life expectancy, V is
the duration of vaccine protection, and ε is the vaccine efficacy.
The important concept of immunization programs of COVID will support the eradica-
tion of an infectious disease. The vaccination drive would be increased in selected sites or
regions, which can escalate the diminishing the positivity rate. As per the literature, Table 6.6
shows the claim of vaccination to improve herd immunity. The herd immunity is the direct
result of vaccines that work and a vaccination rate that is high enough.
The literature reveals that the vaccination and rate of vaccination are primarily used for
the estimation of herd immunity, while low vaccination and low rate of vaccination may
result in the absence of herd immunity in affected and unaffected population. We can see
herd immunity only in the vaccinated population, and the vaccination and rate of vaccina-
tion are highly correlated to high augmentation.
Hospital-based secondary data were collected from Bangalore city; age- and gender-
wise data of vaccination and duration of vaccination and the demographic profile of the
TABLE 6.6
Augmentation of Vaccination and Herd Immunity
Vaccine Vaccination Rate The Effect on Herd Immunity
Low Low No herd immunity
Low High No herd immunity
High Low No herd immunity
High High Herd immunity
patients were collected systematically. The correlation coefficient method was employed
for testing the augmentation of herd immunity and COVID-19 vaccination. The results
found that the age group over 65 years was not statistically significant (r = −0.32, p = 0.644);
the age group 45–55 years showed high-to-medium augmentation (r = 0.74) and 74% of the
population has got herd immunity (doses I & II); and the age group 18–44 years recorded
the highest high-to-high augmentation and 78% population acquired herd immunity after
full dose of COVID-19 vaccination (Table 6.7).
Table 6.8 shows the estimation of vaccine efficacy with or without vaccination in the tar-
get population estimated by the following test statistics (chi-square 2 × 2 contingency table).
N ( ad − bc )
2
χ2 = (6.7)
( a + b )( c + d )( a + c )(b + d )
a / ( a + b)  a c 
Relative risk RR = ; vaccine risk differences =  − .
c / (c + d) ( a + b ) ( d ) 
c +
Vaccine efficacy = (1− RR), where RR is the relative risk factors calculated from 2 × 2
contingency table; unvaccinated event ratio (UER) = (C/C+D); vaccine trial event ratio
(VER) = (A/A+B); relative risk reduction (RRR) = (UER-VER/UER); percentage needed to
be vaccinated in selected clusters = (1/ARR) * 100; if χ 2 cal > χ 2 table ( r−1)(c−1), reject the H0; else
if the calculated chi-square value is less than the chi-square value, accept the H0.
The age group of the patient is the prime factor to correlate the vaccine efficacy. Table 6.9
depicts the statistical observable (diseases spread, vaccination and prevention measures)
components for the determination of the degree of the relation between the two traits. By
using chi-square, we will reject or accept the null hypothesis with df v = (Row-1) * (Column -1).
The formula of chi-square test statistics is as follows:
n
(O − Eij ) 2
∑
ij
χ =
2
(6.8)
i=1
Eij
TABLE 6.7
Augmentation of Vaccination and Herd Immunity
Age class Vaccine Correlation Value Vaccination Rate The Effect on Herd Immunity
>65 years Low −0.32ns Low No herd immunity
45–55 years High 0.74* Medium Herd immunity
18–44 years High 0.78* High Herd immunity
Both doses taken High 0.86** High Herd immunity
TABLE 6.8
Estimation of Vaccine Efficacy in Different Target Populations
Vaccination status Yes No Total
Vaccinated a b (a + b)
Non-vaccinated c d (c + d)
Total (a + c) (b + d) N
TABLE 6.9
Age-Specific Significance of COVID Vaccine Efficacy
Vaccine Efficacy
Age Group <85% 85%–95% >95% Total
Younger age O11 O12 O13 ∑R 1
Medium age O21 O22 O23 ∑R 2
Older age O31 O32 O33 ∑R 3
Total ∑C 1 ∑C 2 ∑C 3 Grand total
where Oij = the observed value of ith row and jth column; Eij = the expected value of ith
Row total*Column total
row and jth column; and Eij = . Inference : if χ 2 cal > χ 2 table ( r −1)( c−1),
Grand total
reject the null hypothesis.
Some vaccination trials correlated the BMI (body mass index, kg/m3) of the target
population with different dosages of vaccination. After complete vaccination of popula-
tion, the researchers should correlate with or without vaccination in association with BMI
(<20 kg/m3, 20–30 kg/m3, and >30 kg/m3). Table 6.10 depicts the statistical components for
the determination of the degree of the relation between the two traits. By using chi-square,
we will reject or accept the null hypothesis (H0) with df v = (Row-1) * (Column-1) by using
the chi-square values in Table 6.10. Inference : χ 2 cal > χ 2 table ( r −1)( c−1) .
Immunization is a highly estimated parameter with comorbidity of the respondents. In
case of COVID-19 pandemic, 65% of the population had two or more underlying comorbidi-
ties and preclinical conditions. As per the literature, comorbidity and side effects of the drug
increased the death rate worldwide. The chi-square and logistic regression methods were
employed on vaccination data sets. The data sets were classified based on the comorbidity
and history of vaccination of the respondent (if the respondent had one or more comorbidi-
ties, he/she was coded as 1, else coded as 0). The logistic regression model was formulated.
 1 
Yt = expo   (6.9)
 1+ e a + b1 X1 + b2 X2 +……bnXn
TABLE 6.10
Vaccination Correlation with BMI
BMI
Vaccination Status <20 kg/m3 20–30 kg/m3 >30 kg/m3 Total
Vaccinated O11 O12 O13 ∑R 1
Non-vaccinated O21 O22 O23 ∑R 2
Total ∑C 1 ∑C 2 ∑C 3 Grand total

 P 
Loigt p = Log  (6.10)
 1 − p 
where a = intercept of the equation; X1, X2…Xn independent variables; and Y is coded as 0
or 1 with the absence or presence of comorbidity (Table 6.11).
The results in Table 6.12 depict the comorbidity and vaccination effects correlated by
using logistic regression model. The research findings show that a significant difference
(p < 0.0001) was found in the respondents that received full dose COVID vaccination of
both Covishield and Covaxin. The hazard ratio with respect to COPD was 3.22 [1.33–6.22,
P = 0.006]; diabetes 1.92 [0.76–2.55, P = 0.012]; hypertension 2.03 [1.53–3.18, P = 0.00]; and
malignant tumor 4.11 [2.85–7.63, P = 0.001]. The person suffering from a preexisting clini-
cal condition or one or more comorbidities was also assessed using the same model. The
respondents who had only one comorbidity had a hazard ratio of 0.92 [0.12–1.22, p = 0.007]
and 2 or more 2.96 [1.33–4.16, p < 0.001].
Table 6.10 clearly depicts that vaccination is the prime factor for the eradication of dis-
ease at the early stage. Early vaccination will reduce the geometric progression of disease.
The immigrants are the bridge population that carry the infection from the different parts
of the world. The concerned government can address the issue by framing separate policy
guidelines for vaccination drive for immigrants and family members. The logistic regression
model was employed to correlate the hypothetical statement of immigrants and COVID-19
vaccination. The results found that 82.0% of immigrants received vaccination and their fam-
ily members’ vaccination status shows a suboptimal figure (Table 6.13). It clearly indicates
TABLE 6.11
Comorbidity with respect to COVID Vaccination
Comorbidity
Vaccination status Yes No Total
Vaccinated O11 O12 ∑R 1
Non-vaccinated O21 O22 ∑R 2
Total ∑C 1 ∑C 2 Grand total
TABLE 6.12
COVID-19 Vaccination Effect on Different Comorbidities
(Private Hospital of Bangalore City, n = 513 cases)
Types of Comorbidity Hazard Ratio (CI 95%) P-Value
COPD 3.22 [1.33–6.22] 0.006
Diabetes 1.92 [0.76–2.55] 0.012
Hypertension 2.03 [1.53–3.18] 0.000
Malignant tumor 4.11 [2.85–7.63] 0.000
Number of comorbidities
1 0.92 [0.12–1.22] 0.007
2 or more 2.96 [1.33–4.16] <0.001
TABLE 6.13
Immigrants with respect to COVID Vaccination
Status Immigrants Family Members of Immigrants Hazard Ratio (CI 95%) P-Value
Vaccinated 82.0% 43% 3.68 [1.22–5.63] ≤0.002
Non-vaccinated 18.0% 67% 8.74 [5.68–10.63] ≥0.001
that the progression originated from the family members and immigrant population, 3.68
[1.22–5.63, p = 0.002]. However, without vaccination of the immigrants (18%), the progression
of disease is more and statistically insignificant; the hazard ratio was 8.74 [5.68–10.63, ≥ 0.001].
Table 6.14 shows the vaccination coverage in India with different geographical regions
affected by COVID; the region or zone was classified based on the infectivity percentage
and prevalence of the disease pandemic. Three zones were identified, viz. high prevalence,
medium prevalence, and low prevalence. Vaccination drive was incepted in the middle
of November 2021 in accordance with WHO guidelines and health policy framework of
Government of India; 54% vaccination was covered in high prevalence states; and the odds
ratio was 6.02 [1.22–5.63, ≤ 0.00]. It was found to be statistically significant. The medium
prevalence region (24%) had an odds ratio of 0.82 [0.10–1.89, p > 0.01]; the low prevalence
region had an odds ratio of 0.68 [0.12–0.99, p > 0.01]. Vaccination in the medium and low
prevalence states is not significantly correlated because of acute shortage of vaccination
and human power. As per the record of MoHFW, Government of India, as of June 13,
2021, a total of 14% (fully vaccinated 3.5%) vaccination was covered in all Indian states
(Figure 6.9). Maximum amount of vaccination drives were conducted in high prevalence
states in the following order: Uttar Pradesh (8.30%), Maharashtra (8.05%), Gujarat (7.78%),
Rajasthan (7.84%), West Bengal (3.98%), Karnataka (7.79%), Madhya Pradesh (8.86%), Bihar
(8.02%), Odisha (7.62%), Andhra Pradesh (7.70%), Kerala (7.52%), Tamil Nadu (7.86%), etc.
Yates chi-square = 750724130.19; Pearson = 750724198.73 (<.0001), odds 0.02, RR = 0.03; log
odds −8.52 (CI 95% 0.02–0.03); vaccine efficacy = 1- RR = (1 − 0.03) = 0.97.
As shown in Table 6.15, on first priority, the MoHFW initiated vaccine drives for frontline
healthcare professionals. Vaccinated data sets were downloaded from the virtual website
of MoHFW, Government of India. The Yates chi-square was employed to test the signifi-
cant difference between the effectiveness and disease progression of COVID-19. The results
found that the proportion of vaccination (1.25) significantly (p < 0.01) reduced the infectivity
in vaccinated population. In case of unvaccinated population, the proportion of infectivity
is very high and found to be statistically insignificant as compared to general population.
We can prevent the spread of COVID-19 pandemic and any infectious disease. The
following parameters should be focused: (i) Immunize against infectious disease, (ii)
wash and dry your hands regularly and well, (iii) stay home if sick, (iv) cover when
you cough and sneeze, (v) clean surfaces regularly, (vi) ventilate the home, (vii) prepare
food safely, and (viii) practice social distancing and safe sex. With respect to the above
TABLE 6.14
Prevalence of Disease with respect to COVID-19 Vaccination
Status % Odds Ratio (CI 95%) P-Value
High prevalence region 54 6.02 [1.22–5.63] ≤0.00
Medium prevalence region 24 0.82 [0.10–1.89] ≥0.00
Low prevalence region 22 0.68 [0.12–0.99] ≥0.00
Control of disease spread−Model
Identify the target population Superseeder,

Symptomatic and Asymptomatic
Vaccinate the already treated or exposed

population by using Virus inactivated
vaccine
Selection of Clusters based on the

prevalence for mass vaccine (High,
Medium and low)
Vaccine should be done for High
risk population (Frontline healthcare
workers) Phase 1
Vaccinate the population on priority basis
(based on age, BMI Phase 2)
Phase 3 (General population)
Assess the vaccinated population
Collection, compilation and report

writing
FIGURE 6.9
Flowchart of the mathematical model with or without vaccination to determine the efficacy of COVID
vaccination.
TABLE 6.15
Vaccination Coverage of COVID-19 Frontline Healthcare Professionals
Vaccination status Healthcare Workers Others Total Rates Odds
Vaccinated 11,116,884 341,572 11,458,456 0.092 0.03
Unvaccinated 8,883,116 1381,609,010 1,390,492,126 0.9931 155.53
Total 20,000,000 1,381,950,582 1,401,950,582
Proportion 1.25 0.002
intervention, inception of vaccination is the reluctant factor to control the spread of

infection. During the process of vaccination, selection of target population is very impor-
tant; as per the regularity guidelines of WHO and concerned ministry of state, vaccina-
tion should be incepted at one time. The graph and flowchart of vaccination are presented
in Figures 6.10 and 6.11.
The COVID-19 vaccine (Sputnik) drive program was conducted in Russia in the mid-
dle of November 2020 (Table 6.16). Vaccinated secondary data sets were collected from
COVID Worldometer. The logistic univariate model was used to test the hypothetical
statement. The results found that the percent of total vaccination in terms of ethnicity
was as follows: Hispanic/Latino was 2.11 ± 0.43 [CI 95% 1.26–2.95, ≤ 0.001]; non-Hispanic/
Latino was 79.14 ± 0.11 [CI 95% 78.92–79.35, ≤0.001]; and unknown origin was 21.73 ± 5.25
Healthcare workers
Those at high risk of acquiring and

transmitting infection including
medical staff from Ministry of Health,
Ministry of Defence, Ministry of Public
Security, laboratory staff, pharmacists,
village health volunteers, healthcare
workers at private health
facilities and medical students
Older adults
People aged 60 years or above. The risk

of severe illness and death from
COVID-19 substantially increases with
older adults
Individual with underlying

health conditions
Those with underlying health

conditions including lung or heart
disease, diabetes, obesity, conditions
that affect the immune system and
others
Essential workers
This group includes workers considered

essential for maintaining the economy
and providing services such that border
control officers, security forces, teachers,
civil servants, judges, transport logistics,
energy mining utilities, finance
communications, customs and others
Essential travelers
Those currently in Lao PDR at

risk of acquiring infection outside
the home country and
reintroducing infections upon return
to home country. This group
includes migrant workers, business
people, diplomats, etc.
FIGURE 6.10
COVID-19 vaccine status in India.
[CI 95% 11.44–32.02, ≤ 0.001]. A similar model was employed for finding the correlation of
race with vaccination. The results showed that in Asian, the mean percent of vaccination
was 1.20 ± 0.22 [CI 95% 0.76–1.63]; in black or African American, the mean percent was
6.58 ± 1.88 [CI 95% 2.85–10.26]; in others/multiracial, it was 10.45 ± 7.58 [CI 95% −4.4–25.30];
in the unknown, it was 21.17 ± 3.56 [CI 95% 14.19–28.14], and in white population, it was
60.25 ± 17.44 [CI 95%; 26.06–94.43]. The gender-wise breakup is presented in Figure 6.12.
9.00
(i)Ethnicity 134263381 98178656
8.00 11255180965340389
14218355 17072875
Hispanic/Latino 2556183
Hispanic/Latino 7.00 402236 2312966 1771105
Unknown 6.00 319083
(ii)Race
5.00
Asian 28972
4.00
Black or African American
Other/Multiracial 3.00
Unknown 2.00
White 1.00
(iii) Gender
0.00
Male
n
Female ow
nkn
O U
U
FIGURE 6.11
Flowchart of the selection of target population for vaccination.
The gender or sex parameter was correlated with the vaccination effect: The male percent
variation was 38.36 ± 0.08 [CI 95% 38.20–38.51]; the female mean was 61.42 ± 7.54 [CI 95%
46.64–76.19]; the “O” mean was 0.012 ± 0.03 [CI 95% −0.046–0.070]; and the “U” mean was
0.019 ± 0.01 [CI 95% −0.006–0.0386]. As per the cited results of Russian vaccination coverage
with different parameters, it was found to be statistically significant (p ≤ 0.001).
TABLE 6.16
Vaccination Coverage in Russia
Percent of Total Percent of Fully
Vaccination (%) CI 95% Vaccinated (%) CI 95%
Category Mean ± SD [Lower–Upper] Mean ± SD [Lower–Upper] P-Value
(i) Ethnicity
Hispanic/Latino 2.11 ± 0.43 [1.26–2.95] 2.02 ± 0.47 [1.09–2.94] ≤0.001
Non-Hispanic/Latino 79.14 ± 0.11 [78.92–79.35] 79.58 ± 0.26 [79.07–80.08] ≤0.001
Unknown 21.73 ± 5.25 [11.44–32.02] 18.30 ± 4.75 [8.99–27.61] ≤0.001
(ii) Race
Asian 1.20 ± 0.22 [0.76–1.63] 1.17 ± 0.32 [0.5428–1.79] ≤0.001
Black or African 6.58 ± 1.88 [2.85–10.26] 6.75 ± 2.46 [1.9284–11.57] ≤0.001
American
Others/multiracial 10.45 ± 7.58 [−4.4–25.30] 13.78 ± 10.17 [−6.15–33.71] ≤0.001
Unknown 21.17 ± 3.56 [14.19–28.14] 11.94 ± 5.06 [2.02–21.85] ≤0.001
White 60.25 ± 17.44 [26.06–94.43] 65.96 ± 18.53 [29.64–102.27] ≤0.001
(iii) Gender
Male 38.36 ± 0.08 [38.20–38.51] 38.36 ± 0.005 [38.35–38.36] ≤0.001
Female 61.42 ± 7.54 [46.64–76.19] 61.56 ± 6.58 [48.66–74.45] ≤0.001
O 0.012 ± 0.03 [−0.046–0.070] 0.010 ± 0.005 [0.00–0.019] ≤0.001
U 0.019 ± 0.01 [−0.006–0.0386] 0.207 ± 0.078 [0.06–0.34] ≤0.001
Source of data: COVID Worldometer, December 17, 2020, to April 19, 2021.
FIGURE 6.12
Vaccination breakup in Russia.
6.7 COVID Vaccination Predictive Statistical Models

The predictive modeling is an unfragile section and deals with the predictive analytics
of massive quantitative data series of research (Dushoff et al., 2007; David, 1981). By using
predictive modeling techniques, we analyze the process of future events or outcomes with
different patterns of forecasted results. The main goal of predictive modeling is to answer
the questions of real problems of COVID-19 pandemic, and also we assessed the past and
future behaviors of disease progression. The predictive model will forecast what is most
likely to happen in the future. From the historical point of view, the predictive modeling
is often associated with many disciplines of science, viz. medical—to forecast the behav-
ior of a disease, engineering—to predict new technological transformation, agricultural
science—to predict the crop yield of various crops, meteorology—to forecast weather, and
business science—in many applications. In case of bigdata analysis, the modelers used
the Web surfers “historical data” running it through algorithms to determine what kind
of products users might be interested in and what they are likely to click on. Many time
series forecasted and naive Bayesian models were demonstrated by the scientists. Th Naive
Bayesian models will help us to identify the real probability that a given COVID projec-
tion point detection and also used to identify the outliers in a data set that point toward
disease sum of behavioral activity (Basavarajaiah and Naraismhamurthy, 2020). The most
complex area of predictive modeling is the neural network. This type of machine learning
model independently reviews voluminous COVID-labeled data when looking for correla-
tion between clinical, epidemiological, genetic, host, and pathogenic parameters. It can
detect even subtle correlation that only emerges after reviewing massive data points of
COVID-19. The algorithms can then make inference about unlabeled data of SUV files that
are similar in type to the data set they were trained on (Castilho et al., 2020; Bauch, 2005).
Neural network is the fundamental technique to postulate artificial intelligence (AI-based

applications), including image recognition, smart assistants, and natural language genera-
tions (NLGs). In the interest of reader, we constructed easiest models of forecasted time
series models to know the behavior of vaccine drive to control the infection of COVID-19
(Bubar et al., 2021; Anderson et al., 2020). The time series vaccination data were down-
loaded from the virtual platform of MoHFW, Government of India. The predictive model
was built and demonstrated by the real data of vaccine.
6.8 Model Construction
The aim of the model is to estimate the current level and to use it to forecast the future
value. This method provides an exponentially weighted moving average of previously
observed values of data sets. The collected data sets were grouped based on different time
periods with respect to infection, active, treated, and death cases. The Holt–Winters expo-
nential model was formulated for initializing the level, trend, and seasonality of the dis-
ease spread. Before the construction of the model, initialize Ls, bs, and Ys and identify those
for initializing the seasonal indices.
1
Ls =
S
( y1 + y2 …ys ) Level initialization
1  y s+1 − y1 y s+ 2 − y 2 y s+ s − y s 
bs =  + +  Trend initialization
s s s s
y1 y2 ys
s1 = , s2 = , ss = Initialization season
Ls Ls Ls
s1 = y1 − Ls , s2 = y 2 − Ls , Ss = y s − Ls
Lt = α ( yt − St−1 ) + ( 1 − α )(α t − 1) + ( bt−1 ) (6.11)
bt = β ( Lt − tt−1 ) + ( 1 − α ) ( 1 − β ) ( bt−1 ) (6.12)
St = γ ( yt − Lt ) + ( 1 − γ ) St− s (6.13)
F(t+ m) = Lt + bt m + St+ m− s (6.14)
The Holt–Winters multiplicative model
yt
Lt = α + ( 1 − α ) ( Lt−1 + bt−1 ) (6.15)
st− s
bt = β ( Lt − Lt−1 ) + ( 1 − β ) ( bt−1 ) (6.16)
 yt 
St = γ   + ( 1 − γ ) St− s (6.17)
 Lt 
F(t+ m) = Lt + mbt + St + m− s (6.18)
where
Lt = level of data series;
yt = actual observed values in period “t”;
β = smoothing constant for trend estimates;
bt = trend estimates;
γ = smoothing constant for seasonality estimates;
St = seasonal components estimates;
m = the number of periods in the forecast lead period; and
F(t+ m) = forecast for mth period in the future.
This is an obvious extension to the moving average method. With simple moving average
forecasts, the mean of the past k observations used as a forecast has equal weights (1/k) for
all k data points. With exponential smoothing, the idea is that the most recent observations
will usually provide the best guide as to the future, so we want a weighting scheme that
has decreasing weights as the observations get older.
Table 6.17 accounts for the fact that COVID-19 data points were initialized based on the
cited equations (6.11–6.14). The model was smoothened to compare the actual and fitted
observations of data series of COVID and also the behavior of disease progression. Table
6.17 represents the observed cases of COVID among high prevalence states of India. The
highest number of cases was recorded in Maharashtra state (11,447,503) with a weighted
average initialization [X (n + 1) p] of 270,249. It was assumed that after 6 months of outbreak,
the infectivity will reduce and the disease may reach the lowest epoch and lead to nor-
malcy. The residual and seasonality effects were seen in the following states: Chhattisgarh
(653,147 cases), Kerala (881,613 cases), Gujarat (4,599,688 cases), Rajasthan (5,141,908 cases),
Karnataka (2,036,472 cases), Maharashtra (6,706,429 cases), Madhya Pradesh (1,832,064
cases), West Bengal (2,896,101 cases), Bihar (372,940 cases), and Uttar Pradesh (4,601,737
cases). It was estimated that the second phase of infection started with a lag period of
3–4 months; it was incepted approximately in the period between the middle of February
2021 and the second week of March 2021. It was predicted that almost all Indian states will
be significantly affected by the second phase (II wave) of COVID-19 infection at an average
rate of 270,249 cases per day.
In the mathematical field of numerical analysis, interpolation is a method for con-
structing new data points within the ranges of discrete sets of known data points of
COVID. However, the techniques of interpolation pass exactly through the observed
data points, for example a polynomial with a sufficient degree (the number of points less
than one) or a Fourier trigonometric expansion (if the function is assumed periodic). The
forecasting methods are approximations. They do not pass exactly through the observed
TABLE 6.17
Interpolation of Model–Expected Cases of Susceptible Population
State Observed Fitted Residuals
Chhattisgarh 4,561,972 413,625 653,147
Kerala 5,443,585 4,561,972 881,613
Gujarat 9,181,707 4,582,018 4,599,688
Rajasthan 9,828,519 4,686,610 5,141,908
Delhi 2,238,274 4,803,532 −2,565,258
Karnataka 6,781,674 4,745,201 2,036,472
Odisha 4,499,013 4,791,508 −292,495
Haryana 2,859,343 4,784,857 −1,925,514
Maharashtra 11,447,503 4,741,073 6,706,429
Madhya Pradesh 6,725,635 4,893,570 1,832,064
West Bengal 7,831,331 4,935,229 2,896,101
Punjab 2,352,743 5,001,083 −2,648,340
Telangana 2,862,110 4,940,863 −2,078,753
Jharkhand 2,477,789 4,893,594 −2,415,805
Tamil Nadu 4,187,801 4,838,661 −650,860
Bihar 5,196,802 4,823,861 372,940
Assam 1,416,049 4,832,342 −3,416,293
Uttar Pradesh 9,356,397 4,754,659 4,601,737
Semi-interquartile difference (weighted average at X (n+1)p) is 270,249; Durbin–Watson value = 23.66; R2
(%) = 0.93.
points, but nearby, which allows for the function to be smoother. Furthermore, the Holt–
Winters method is discrete. It does not give an approximate value for time in between
observed data points, but gives point for the next time values. Hence, the word would
be extrapolation (extra = out of) rather than intrapolation (intra = inside). But it is not an
extrapolation because it is an approximation rather than exact values. In this analysis,
we developed a novel concept of intrapolation techniques. In the first 6 months of COVID
outbreak, the same rapid outbreak trend and more disease variation will be maintained
irrespective of geographical region. The residual cases driven by intrapolation tech-
niques are presented in Table 6.17.
Figure 6.13 shows the extrapolation of COVID-19 outbreak in last week of April 2021;
the techniques of extrapolation escalate the estimation of a value based on extending a
known sequence of values or facts beyond the area that is certainly known. In a broad
sense, both extrapolation and intrapolation are used to estimate hypothetical values for a
variable based on other observations. There are a variety of intrapolation and extrapola-
tion methods based on the overall trend that is observed in the data. These two methods
have names that are very similar. We will examine the difference between them. For both
methods, we assume a few things. Eventually, we identified an independent variable and
a dependent variable. Through sampling or collection of data, researchers should make a
number of pairing of the selected variables. However, we also assume normalcy and least
square line or best fit of data sets. The model results mainly help to extrapolation of pan-
demic of COVID depicted from the constructed model, after a month of rapid outbreak,
is that the disease will reach normalcy or flatten the curve inclusion with effective policy
intervention and prevention strategies.
FIGURE 6.13
Extrapolation of COVID-19 as of April 2021.
ACF residual plot is used to test the common variations and the joint hypothesis of
observed and theoretical values in the specified order of lag period. The upper plot is
noise independent, and the lower one is a random walk (those differences are the origi-
nal series). It has a very strong autocorrelation. The following ACF formula is used to
test the hypothesis:
t − S− 1
rxx( n) =
1
N ∑ x ( k ) ⋅ x ( k + n)
K =0
(6.19)
By using equation (6.19), we can characterize the data which show the degree of similarity
between the values of the same variables over successive time intervals. This equation (6.19)
explains the variations in the predicted and observed components of discrete data series.
When we extrapolate a series of numbers of data points, and there is a pattern such that
the values in the given series can be forecasted based on the preceding values in the series,
the series of points are said to exhibit autocorrelation residual plots. This is also known as
serial correlation and serial dependency of disease progression. The existence of ACF in
the residual plot representation may be sound. Autocorrelation is diagnosed using a cor-
relogram (ACF plot) and can be tested using the Durbin–Watson test statistics. Figure 6.14
shows the positive first-order linear correlation and indicates that the observations that are
one apart are correlated, and positive means that the correlation between the observations
is positive. When data exhibiting positive first-order correlation are plotted, the points
appear in a straight line or snake-like curve, as on the left. With negative first-order cor-
relation, the points form a zigzag pattern if connected, as shown on the right-hand side of
the graph. Figure 6.15 also depicts a correlogram, and it gives a summary of correlation at
different periods of time. The plot shows the correlation coefficient for the series lagged
(in distance) by one delay at a time. For example, at Xi = 1,2,3, you might be comparing the
data points of COVID-19 cases of January 2021 to February 2021 or February 2021 to March
2021. The horizontal scale is the time lag and the vertical axis is the ACF. The plot is often
FIGURE 6.14
Residual plot of COVID-19 pandemic in India as of April 21, 2021.
Mathematical model
Susceptible
Population Vaccinated
(Sij)
Vaccination of COVID
Respondent selected based on age specific and gender matched
High prevalence Medium Prevalence Low Prevalence

probability (H)
Spread (S) Primary infection (Pi)
Incubation Period (Ip) End of infection (Ie)
Tt
Transmission time line
Clinical time line
Ct Incubation Period (Ip)
Onset of symptoms S0 Symptomatic period (St ) Recovered Rt
FIGURE 6.15
Interpolation of vaccine coverage in India as of April 21, 2021. (Source: COVID-19 India.Org, Union Health
Ministry, GOI.)
combined with a measure of ACF such as Moran’s I: Moran’s values close to +1 indicate
clustering, while values close to −1 indicate dispersion. Figure 6.12 shows a relatively large
Moran’s value (between about 0.2–1.4). In addition, there is a strong pattern of disease
behavior seen in the selected sites of Indian states.
The estimation of population-level quintiles or percentiles is of great concern, particularly
in computational biology, public health, and infectious disease pandemic, when the statisti-
cian is unwilling to assume a parametric form for the distribution or even to assume the
distribution to be symmetric. Sample quintile have many desirable properties. However,
they also have some drawbacks. They are not particularly efficient estimators of location
of distribution such as normal; good estimators of the variance of sample quintiles do
not exist for general distribution; sample quintiles may not be jackknifed; and the sample
median differs in form and in efficiency depending on the sample size being even or odd.
In this rationality of the study, Harrell and Davis (1982) proposed the model Harrell–Davis
quintiles (Table 6.18). Theoretically, we consider y = y ( 1) ≤ y ( 2 ) ≤ …. ≤ y ( n) be a sample of
“n” independent sorted clusters selected for COVID vaccination (i.e., n-order statistics). The
sample was drawn from the same underlying continuous distribution of no specific form.
We seek to use “y” number of respondents selected for vaccination and to estimate the 100
τth quantile (percentile) or potency of vaccination used for immunization drive, Q(τ): Prob
[y ≤ Q(τ)] = τ, where τ (tau) is in (0, 1). For the median (τ = 0.50), when N is odd, the ordinary
estimate is the middle value, y [n/2 + 1]. When N is even, we take the average of the two
middle values. For other quintiles (τ ≠ 0.50), the ordinary estimator is a weighted average of
the two observations closest in rank corresponding to τ. For example, we selected N = 10
clusters for COVID-19 vaccination and we are able to estimate the default ordinary estima-
tors for Q(0.80) in R score quintiles. The function of ordinary quintile is (0.80,10) = 0.80 y
(8) + 0.20y (9).
Tp = ( 1 − g ) X ij + g X j+1 (6.20)
where (n+1) p = j+ g and “j” is the integral part of (n + 1) p when p = 1/2. Tp is the usual
sample median.
HD estimation uses a weighted average of all the data series of COVID vaccination series
set by a complex function that depends only on τ and n. The different quintiles of vaccina-
tion numerals shown in Table 6.18 range from 0.01 to 0.90.
n n
Dijkl = Si ∑( A
i=1
si + Sj *) ∑( H
i=1
ij )
+ Lij Vijk = Tt + Ct (6.21)
Tt = ∑I ( I + P )δ − I
i=1
p ij e
Tt = ∑I (S − S ) R
i=1
p t 0 t
where
S(t) = S(0)expon − R0
( R(t) − R(0)) (6.22)
N
TABLE 6.18
Harrell–Davis Quintiles of Vaccination Coverage in India
Quintiles Value Standard Error (SE)
0.01 1,455,160 748,911
0.02 1,506,810 712,492
0.03 1,568,810 669,080
0.04 1,638,550 620,907
0.05 1,713,280 570,398
0.06 1,790,470 519,967
0.07 1,867,910 471,868
0.08 1,943,890 428,102
0.09 2,017,190 390,366
0.1 2,087,110 360,008
0.11 2,153,350 337,966
0.12 2,216,000 324,687
0.13 2,275,430 320,078
0.14 2,332,160 323,544
0.15 2,386,870 334,140
0.16 2,440,260 350,773
0.17 2,493,030 372,372
0.18 2,545,870 397,974
0.19 2,599,360 426,738
0.2 2,654,040 457,931
0.21 2,710,340 490,891
0.22 2,768,600 524,999
0.23 2,829,090 559,664
0.24 2,891,980 594,307
0.25 2,957,360 628,367
0.26 3,025,250 661,302
0.27 3,095,620 692,603
0.28 3,168,370 721,805
0.29 3,243,360 748,505
0.3 3,320,410 772,373
0.31 3,399,310 793,170
0.32 3,479,860 810,753
0.33 3,561,800 825,089
0.34 3,644,910 836,250
0.35 3,728,980 844,418
0.36 3,813,780 849,877
0.37 3,899,150 853,003
0.38 3,984,910 854,247
0.39 4,070,960 854,122
0.4 4,157,200 853,174
0.41 4,243,600 851,966
0.42 4,330,140 851,047
0.43 4,416,860 850,930
0.44 4,503,810 852,069
0.45 4,591,090 854,835
(Continued)

0.46 4,678,830 859,506
0.47 4,767,170 866,258
0.48 4,856,280 875,162
0.49 4,946,320 886,189
0.5 5,037,470 899,225
0.51 5,129,910 914,083
0.52 5,223,820 930,525
0.53 5,319,370 948,280
0.54 5,416,700 967,060
0.55 5,515,980 986,581
0.56 5,617,320 1,006,570
0.57 5,720,840 1,026,800
0.58 5,826,620 1,047,030
0.59 5,934,760 1,067,110
0.6 6,045,300 1,086,880
0.61 6,158,290 1,106,220
0.62 6,273,730 1,125,040
0.63 6,391,610 1,143,220
0.64 6,511,920 1,160,660
0.65 6,634,580 1,177,200
0.66 6,759,500 1,192,680
0.67 6,886,560 1,206,820
0.68 7,015,610 1,219,340
0.69 7,146,440 1,229,850
0.7 7,278,830 1,237,910
0.71 7,412,510 1,243,030
0.72 7,547,180 1,244,700
0.73 7,682,540 1,242,400
0.74 7,818,240 1,235,680
0.75 7,953,970 1,224,120
0.76 8,089,410 1,207,460
0.77 8,224,300 1,185,590
0.78 8,358,440 1,158,620
0.79 8,491,710 1,126,870
0.8 8,624,140 1,090,990
0.81 8,755,860 1,051,890
0.82 8,887,180 1,010,850
0.83 9,018,600 969,479
0.84 9,150,760 929,777
0.85 9,284,460 894,080
0.86 9,420,610 865,023
0.87 9,560,160 845,400
0.88 9,704,010 837,913
0.89 9,852,880 844,800
0.9 10,007,200 867,445
(Continued)

0.91 10,166,800 906,075
0.92 10,330,900 959,665
0.93 10,498,100 1,026,040
0.94 10,665,800 1,102,090
0.95 10,830,600 1,184,000
0.96 10,988,200 1,267,460
0.97 11,133,800 1,347,930
0.98 11,261,900 1,420,920
0.99 11,367,900 1,482,360
S(0) = the initial number of vaccines scheduled to the susceptible population;

R ( 0 ) = the initial number of cases removed from the vaccination drive due to pre-
clinical conditions based on historical data;
N = the number of respondents who attended the vaccination drive;
R0 = the basic reproduction number;
S ( t ) = the number of susceptible population at time “t”;
R ( t ) = the number of removed individuals as a function of time “t”.
Dijk = Tt + Ct
where
Dijkl = vaccination dose distributed in ith region at jth cluster with kth respondent in
low, medium, or high prevalence area;
Si = disease spread in ith region at jth cluster with kth respondent;
Asi = asymptomatic population at ith region;
Sj = symptomatic population at ith region;
Vijk = vaccination incepted in ith region at jth cluster with kth respondent in low,
medium, or high prevalence area;
H ij = high prevalence area of ith state;
Lij = low prevalence area of ith state;
Pij = proportion of population selected from ith state with jth cluster for vaccine;
I = proportion of population infected from COVID;
δ = rate of change of infection;
I e = proportion of population reached the end of infection;
Tt = timeline for transmission = the time line for clinical process; and
Rt = recovered from COVID at time “t” (Table 6.19).
TABLE 6.19
COVID-19 Vaccination Coverage in India
Total Population I Dose (No.) %I II Dose % Change from
UT/State of India (2011 Census) (n1) Dose (No.) (n 2) I to II Dose
A&N Islands 380,581 87,865 23.09 9,527 0.06
Andhra Pradesh 49,577,103 4,547,958 9.17 1,130,670 2.41
Arunachal Pradesh 1,383,727 163,544 11.82 46,801 0.08
Assam 31,205,576 1,605,276 5.14 415,466 0.84
Bihar 104,099,452 5,534,725 5.32 902,757 3.26
Chandigarh 1,055,450 140,795 13.34 37,860 0.07
Chhattisgarh 25,545,198 4,746,298 18.58 616,149 2.91
Dadra & Nagar Haveli 585,764 38,333 6.54 7,523 0.02
Daman & Diu 52,076 38,575 74.07 6,022 0.02
Delhi 16,787,941 2,425,355 14.45 578,140 1.30
Goa 1,458,545 241,453 16.55 62,556 0.13
Gujarat 60,439,692 9,550,111 15.80 1,988,252 5.33
Haryana 25,351,462 3,057,744 12.06 480,182 1.82
Himachal Pradesh 6,864,602 1,363,254 19.86 185,235 0.83
Jammu & Kashmir 12,267,032 1,731,794 14.12 311,992 1.00
Jharkhand 32,988,134 2,558,664 7.76 419,195 1.51
Karnataka 61,095,297 7,495,249 12.27 1,178,345 4.45
Kerala 33,406,061 5,801,268 17.37 1,045,794 3.35
Ladakh 274,000 71,731 26.18 25,222 0.03
Lakshadweep 64,473 17,492 27.13 3,807 0.01
Madhya Pradesh 72,626,809 6,949,737 9.57 958,928 4.22
Maharashtra 112,374,333 12,404,727 11.04 1,937,989 7.38
Manipur 2,570,390 126,565 4.92 55,981 0.05
Meghalaya 2,966,889 158,278 5.33 51,897 0.07
Mizoram 1,097,206 170,859 15.57 40,378 0.09
Nagaland 1,978,502 137,580 6.95 35,067 0.07
Odisha 41,974,219 4,736,047 11.28 794,127 2.78
Pondicherry 1,247,953 162,204 13.00 20,098 0.10
Punjab 27,743,338 2,676,408 9.65 318,959 1.66
Rajasthan 68,548,437 10,388,447 15.15 1,959,506 5.94
Sikkim 610,577 153,939 25.21 31,956 0.09
Tamil Nadu 72,147,030 4,388,488 6.08 962,896 2.41
Telangana 35,003,674 3,559,283 10.17 512,340 2.15
Tripura 3,673,917 524,664 14.28 196,271 0.23
Uttar Pradesh 199,812,341 9,783,416 4.90 2,000,464 5.48
Uttarakhand 10,086,292 1,530,925 15.18 337,062 0.84
West Bengal 91,276,115 8,243,729 9.03 1,725,523 4.59
Miscellaneous 1,651,006 0 1,254,503 0.28
Total 1,210,620,188 118,963,786 14.15 22,645,440 1.79
Independent Bayesian sample test
t = 1.36; B10 = 1405e−10; error (%) (31.28%); p = 0.085
Data source: As of April 26, 2021, 07:00 AM; https://www.mohfw.gov.in.
6.9 Projection Modeling of COVID Vaccination

The vaccination process and the effect of vaccination involved in the COVID pandemic
crisis remain difficult to understand for public health specialists and clinical microbi-
ologists. Recent developments in high-throughput technologies urge the public health
science to achieve more precise models for complex analysis of COVID data sets. The
computational and projection models allow us to explore the efficacy of vaccination
and to know the side effects, potency of vaccination, and selection of target population
for vaccination drive. In this view, in the present section, we develop projection models
of COVID vaccination and provide the key to addressing the variation of vaccination
coverage in Indian setup. Let x0,x1,x2…xn be the independent variation regressed with
dependent variable of vaccination incepted at time “t” in the selected region of Indian
states (low, medium, and high prevalence states). The secondary data sets of vaccination
were collected from the MoHFW, Government of India, and the necessary data inputs
were downloaded from the virtual platform. The model was constructed and smooth-
ened using R statistical software.
Yt = a + b0 X 0 + b1 X 1 + bn X n + eij (6.23)
t = a + b0 X 0′ + b1 X 1′ + …bn X n′ + eij
Y (6.24)
where Yt = effect of vaccination in the selected region;

X 0 , X 1 , X 2 …X n are the independent variables;
b0 , b1 bn are the coefficients of “X”; and
eij = errors associated with the observed value of ith vaccination in jth location.
n n
1
∑ 1
∑(Y − Y )
2
2 2
se = ei = t t (6.25)
n−2 i=1
n−2 i=1
The F-test for overall significance for vaccination drive is carried out.
Thus, the F-statistic is ratio of two mean square errors. The numerator refers to the vari-
ance that is explained by the regression, and the denominator refers to the variance of
what is not explained by the regression, namely the error components eij .
Explained MS explained SS / explaineddf

F= =
Unexplained MS unexplained SS / unexplaineddf
∑ (Yˆ − Y ) ( m − 1)
n 2
t
i=1
F=
∑ (Y − Y ) n − m
n 2
t t
i=1
MS = the mean sum of squares, SS = the sum of squares, df = degrees of freedom, and m =
the number of parameters (coefficients) in the regression equation.
In fact, the F-statisticishighly connected to the coefficient of determination. Thus, it is
easy to develop another computational formula for F-statistics as follows:
∑ (Yˆ − Y ) / k
n 2
t
i=1
F= (6.26)
∑ (Y − Y ) n − k − 1
n 2
t t
i=1
1 X2
SE ( a ) = σ e + (6.27)
∑( X − X )
2
n i
X2
SE ( b ) = σ e
∑ (X − X )
2
i
∑ (Y − Y )
2
t t
Standarddeviation of error = Sc = (6.28)
n−2
6.10 Model Output
Sum of X1 = 537.93
Sum of X2 = 67.58
Sum of Y = 2011
Mean X1 = 14.5386
Mean X2 = 1.8265
Mean Y = 54.3514
Sum of squares (SSX1) = 4940.2376
Sum of products (SPX1Y) = 81.7176
Sum of products (SPX2Y) = −30.7543
Sum of products (SPX1X2) = −210.3894
Regression equation = ŷ = b1X1 + b2X2 + a
b1 = ((SPX1Y)*(SSX2) − (SPX1X2)*(SPX2Y))/((SSX1)*(SSX2) − (SPX1X2)*(SPX1X2)) = 5867.4/701617.55 =
0.00836
b2 = ((SPX2Y)*(SSX1) − (SPX1X2)*(SPX1Y))/((SSX1)*(SSX2) − (SPX1X2)*(SPX1X2)) = −134741.16/701617.55 =
−0.19204
a = MY−b1 MX1−b2 MX2 = 54.35 − (0.01*14.54) − (−0.19*1.83) = 54.58053
ŷ = Dose (I) 0.00836X1 – (Dose II) 0.19204X2 + 54.58053 age
Sum of X1 = 2011
Sum of X2 = 1343
Sum of Y = 537.93
Mean X1 = 54.3514
Mean X2 = 36.2973
Mean Y = 14.5386
Sum of products (SPX1Y) = 81.7176
Sum of products (SPX2Y) = −30.3851
Sum of products (SPX1X2) = 83.1351
Regression equation = ŷ = b1X1 + b2X2 + a

b1 = ((SPX1Y)*(SSX2)−(SPX1X2)*(SPX2Y))/((SSX1)*(SSX2) − (SPX1X2)*(SPX1X2)) = 46468.04/328864.43 = 0.1413
b2 = ((SPX2Y)*(SSX1) − (SPX1X2)*(SPX1Y))/((SSX1)*(SSX2) − (SPX1X2)*(SPX1X2)) = −25767.06/328864.43 =
−0.07835
a = MY − b1 MX1 − b2MX2 = 14.54 − (0.14*54.35) − (−0.08*36.3) = 9.70284
ŷ = 0.1413X1 − 0.07835X2 + 9.70284
Table 6.20 demonstrates our predictive model approach to COVID vaccination in Indian
setup. The vaccination program and selection of target population were found to be sta-
tistically significant (F = 9.17049; p = 0.000, R 2 = 0.93). The initial stage of vaccination drive
shows a reduction in disease transmission, and vaccination prevents the disease spread
after the second dose by 93%, and approximately 0.14% will be affected by drug-induced
side effects. The respondents may have some side effects, which are normal signs that
your body is building protection. These side effects may affect the ability to perform daily
activities, but they should go away in a couple of days or 1 week. Some people have no side
effects. Common side effects are presented in Figure 6.6.
Using equations (6.23 and 6.24), we demonstrate the real data of vaccination in Table 6.15.
The average vaccination was 14.53% with SD 11.71 in the first dose, and the mean incre-
mental change between the first dose and the second dose was 1.82% with SD 2.04. The
research findings is not found to be statistically significant Indian vaccination drive com-
pared with general population and hazard risk of disease and reproduction rate. At this
stage (as of April 26, 2021), the average expected vaccination coverage was expected to be
27.57% with SD 11.67 (Table 6.21). The important benefits of vaccination are the following:
(i) prevention from getting ill—based on what we know about vaccines for other diseases
and early data from clinical trials, experts believe that getting COVID-19 vaccine may also
help prevent the person from getting seriously ill even if you do get COVID-19; (ii) protec-
tion to others—if a person gets vaccinated, he/she may also protect people around them,
particularly people at increased risk of severe illness from COVID-19; (iii) ability to be pre-
pared for the unknown—COVID can have serious, life-threatening complications, there is
no way to know how COVID will affect the person, and the infected person will spread the
disease to friends, family, and others; (iv) boosted immune system. Wearing masks, main-
taining social distancing, and washing hands help reduce the chance of being exposed to
the virus or spreading it to others, but these measures are not enough. Vaccines will work
with the immune system, so it will be ready to fight the virus if the person is exposed,
finally stopping the spread (Table 6.22).
TABLE 6.20
Significant Changes of I Dose of Vaccination with Respect to II Dose
Sample Variance
c d Total
N 37 37 74
∑X 241.4751 62.1784 303.6535
Mean 6.5264 1.6805 4.103
∑X2 4,940.2376 150.9808 5,091.2185
Std. Dev. 9.6671 1.1364 7.2577
Source SS df MS
Between treatments 434.4233 1 434.4233 F = 9.17049
Within treatment 3,410.7755 72 47.3719 R2 = 0.93
Total 3,845.1988 73
TABLE 6.21
Forecasting Figures of Phase I Vaccination Coverage in India
Total
Weighted Cumulative Next Predicted Vaccination
UT/State of (%) I (%) II Mean Mean Age for Next Phase Vaccination for Next
India Dose (a) Dose Age (60% Weightage) Coverage (b) Phase (a + b)
A&N Islands 23.09 0.06 45 33 11.64 34.73
Andhra Pradesh 9.17 2.41 42 34 11.34 20.51
Arunachal 11.82 0.08 55 28 13.12 24.94
Pradesh
Assam 5.14 0.84 60 33 13.88 19.02
Bihar 5.32 3.26 48 34 12.22 17.54
Chandigarh 13.34 0.07 57 36 13.39 26.73
Chhattisgarh 18.58 2.91 54 40 12.98 31.56
Dadra & Nagar 6.54 0.02 56 42 13.30 19.84
Haveli
Daman & Diu 74.07 0.02 54 34 12.58 86.65
Delhi 14.45 1.3 55 35 13.12 27.57
Goa 16.55 0.13 53 36 12.81 29.36
Gujarat 15.8 5.33 54 34 13.03 28.83
Haryana 12.06 1.82 56 32 13.29 25.35
Himachal 19.86 0.83 54 37 12.94 32.80
Pradesh
Jammu & 14.12 1.00 57 34 13.40 27.52
Kashmir
Jharkhand 7.76 1.51 54 36 13.03 20.79
Karnataka 12.27 4.45 56 35 13.33 25.60
Kerala 17.37 3.35 58 38 13.56 30.93
Ladakh 26.18 0.03 58 39 13.45 39.63
Lakshadweep 27.13 0.01 59 41 13.59 40.72
Madhya Pradesh 9.57 4.22 56 42 13.34 22.91
Maharashtra 11.04 7.38 53 32 12.95 23.99
Manipur 4.92 0.05 54 35 13.03 17.95
Meghalaya 5.33 0.07 54 30 13.02 18.35
Mizoram 15.57 0.09 52 34 12.68 28.25
Nagaland 6.95 0.07 55 34 13.15 20.10
Odisha 11.28 2.78 53 33 12.88 24.16
Pondicherry 13 0.1 52 34 12.69 25.69
Punjab 9.65 1.66 54 35 13.02 22.67
Rajasthan 15.15 5.94 57 36 13.47 28.62
Sikkim 25.21 0.09 58 37 13.46 38.67
Tamil Nadu 6.08 2.41 56 38 13.34 19.42
Telangana 10.17 2.15 62 40 14.15 24.32
Tripura 14.28 0.23 61 42 13.95 28.23
Uttar Pradesh 4.9 5.48 54 43 13.11 18.01
Uttarakhand 15.18 0.84 47 43 11.98 27.16
West Bengal 9.03 4.59 48 44 12.22 21.25
Data source: As of April 26, 2021, 07:00 AM; https://www.mohfw.gov.in.
TABLE 6.22
Differences between Classical and COVID-19 Vaccines
Classical Vaccines COVID-19 Vaccines
Preclinical stage (18–30 months) Preclinical stage (0 months)
Phase I (dozens of volunteers in 30 months) Phase I (dozens of volunteers in 6 months)
Phase II (hundreds of volunteers in 32 months) Phase II (hundreds of volunteers in 6 months)
Phase III (thousands of volunteers in 30 months) Phase III (thousands of volunteers in 0 months)
Approval, manufacture of vaccination (12–24 months) Approval, manufacture of vaccination (billions of doses/
individuals in 6 months)
FIGURE 6.16
Clinical trial of COVID-19 vaccination from phase I to phase IV.
Phase I—safety (evaluate safety and identify common reactions); phase II—effectiveness
(gather information on safety, efficacy, dosage, and reaction); phase III—safety +
effectiveness (compare thousands of volunteers with those who did not get vaccination);
and phase IV—safety + effectiveness (continue to study safety, long-term benefits, and
side effects) (Figure 6.16).
6.11 Real Probability of Bayes for Estimation of Vaccination Effect

The policy decision maker should always be aware of additional information that might
be used to navigate the decision-making process of pandemic crisis opined that, Bayes
probability values is usually good information on vaccination, furnish the policy-making
guidelines and formulate the vaccination algorithms. Hence, the discretion must be used in
selecting information. Quite often, it is possible to obtain the reliable information about the
state of nature so that a state of vaccination can be studied by the dimensionality approach;
for example, suppose we know the distribution of random variables X1,X2,X3…Xn, which
are the numerical figure of percentage expression of vaccination done in different states and
UTs (30 states and UTs were considered for the study) considered for the state of nature θ .
Negative attitude towards vaccine and an uncertainty or unwillingness to receive vaccina-
tion are the major barriers to managing the COVID-19 pandemic in the long term. Figure 6.17
clearly describes the acceptance level of COVID vaccines (Figure 6.18).
Phase I
Phase IV Phase II
Phase III
FIGURE 6.17
Attitude toward COVID-19 vaccination at inception of vaccination drive.
FIGURE 6.18
Quintile changes in vaccination coverage in India.
6.12 Bayes Stochastic Vaccination Model

( )
In particular, QX X n / θ 0 = θ j is the conditional distribution of given random variables
( )
θ 0 = θ j . We can use this information, and the prior distribution of “θ ” is a function of “xs”.
This adopted distribution is called posterior distribution. The Bayes decision procedure
with real data is to obtain the prior and posterior distributions of conditional probability
function with varying values of α and β (Table 6.23).
TABLE 6.23
Model Output of Bayesian Analysis
Posterior Overall
Models Posterior Mean Prediction Success Prediction Epoch
II dose Spike at 0.85 vaccination prevents 0.85 BD (10 high COVID 9.31
disease prevalence states, 0.85)
Spike at 0.15 vaccination prevents 0.15 BD (10 high COVID 1.68
hazard risk of vaccination prevalence states, 0.15)
I dose Spike at 0.50 vaccination prevents 0.50 BD (10 high COVID 4.98
disease prevalence states, 0.50)
θ = Random variables represented thestateof nature

X n = random variablethat related toθ
Pθ (θ J ) = Priordistribution of θ
QX ( X n /θ 0 = θ j ) = (θ 0 = ( 1 − α ) = β Conditional distribution of ‘X ’ given θ 0 = θ j
( )
hθ = (θ i /X = x ) ; hθ = θ j /X = x Conditional distribution of θ
g X ( x ) = Marginal distribution of θ
( )
f xθ x , θ j = Joint distribution of X and θ
( ) (
f xθ x , θ j = ω x X n /θ 0 = θ j Pθ ) (6.29)
gX ( x ) = ∑f
i=1
xθ ( x,θ )
j
∑ω ( X /θ
i=1
x n 0 )
= θ j Pθ (θ i )
ω x ( X n /θ 0 = θ j ) Pθ (θ i )
hθ = (θ i /X = x ) = (6.30)
∑
n
ω x ( X n /θ 0 = θ k ) Pθ (θ k )
i=1
The Bayesian stochastic model is constructed in equations (6.29 and 6.30). The numeri-
cal simulation was demonstrated by real data sets of COVID vaccination (obtained from
virtual platform of MoHFW, Government of India). The compilation was done using JASP
statistical software. In Model 1 (dose1) we assumed that the spike of COVID (p = 0.85) vac-
cination probability prevents disease, spike at 0.50 vaccination probability prevents haz-
ard risk of vaccination (coded as 1 and 2). The model was simulated using Monte Carlo
simulation techniques with shape and scale parameters of alpha and beta. As per the
model input, the formulated model (Model 1) is the best fit for propagating the posterior
and prior information of vaccination to prevent the disease process. The first dose of vac-
cination converges on a smaller proportion of the population, thereby boosting immunity.
In persons who received both doses of vaccination it really converges a positive effect of
immunogenesis (an antigen capable of an indicing an immune response) of the population.
Approximately R 2 = 94.57% acquired immunity after the vaccination, which prevented the
disease transmission to others (Table 6.24).
TABLE 6.24
Proportion of Success of Vaccination in Indian States
Proportion of Success Model 2 (Dose 2) Model 1 (Dose 1)
0.00 5.7 e−9 9.70e−04
0.10 3.2e−9 0.010
0.20 8.3e−7 0.044
0.30 1.25e−6 0.117
0.40 0.001e−4 0.205
0.50 0.008 0.246
0.60 0.040 0.206
0.70 1.30 0.117
0.80 0.276 0.044
0.90 0.047 0.010
1.00 0.97 9.76e-4
R2(%) 94.57% 76.85%
6.13 Discussion
Mathematical and statistical models will help us assess and build effective COVID-19
pandemic vaccination strategies. A simple analytical model gives insights into the coun-
terintuitive effects of the present vaccination drive to control the pandemic crisis of
COVID-19 worldwide. We had only one vaccination strategy or tool to eradicate the dis-
ease from the vaccination drive. Many countries have already started vaccination drives
at the coverage rate of 75%–85% (Kahn et al., 2021; Julio et al., 2021; Hethcote and Waltman,
1973). The present study demonstrates both statistical and mathematical models to
extrapolate the variations of disease progression and how vaccination controls the pan-
demic of disease. Many scientists at the global platform formulated new innovative vac-
cination mathematical models. Nuraini et al. (2020) derived mathematical models for
assessing vaccination scenarios in several provinces in Indonesia. This study provided
measures to mitigate casualties due to COVID-19 outbreak and also assessed the optimal
vaccination scenarios considering some existing healthcare conditions such as suscepti-
ble, infected, quarantined, recovered, and COVID-induced death. The models included
an age-structured dynamic transmission model that naturally could give different treat-
ments among age groups of population. The model simulation shows that the timing and
the duration of the vaccination drive should be well planned and prioritizing particular
age groups will have a significant impact on the total number of casualties. The present
study is comparable to models with age-specific vaccination drive and will help to reduce
the infection rate; importantly, the selection of target population is the prime indicator
for COVID-19 vaccination drive. Vasiliki Bitsouni et al. developed a compartmental
mathematical model with the demographic profile of the population of COVID-19, con-
sidering asymptomatic infectious individuals. They computed the basic reproductive
ratio of the model and studied the local and global stabilities for the disease spread;
finally, they proposed a new vaccination model and derived threshold conditions for
preventing infection spread in the case of an imperfect vaccination drive conducted in
Italy. Only effective vaccination drive can reduce the risk of infection spread, the peak
prevalence of infection, and the time at which the peak prevalence occurs (McLean 1995;
Khachatryan et al., 2020). As per the editorial remarks of Elsevier, vaccination is the pri-
mary tool for eradicating infectious diseases. Scientific findings suggest that pathogens
often have the potential to spread rapidly, because of their short generation time, large
population size, and high rates of mutation. Vaccination specialists commonly believe
that the use of vaccines will typically result in novel selective pressure on pathogen pop-
ulation, often resulting in the emergence of resistant genotypes. One more study reported
by Nuraini et al. (2020) on COVID vaccine resulted in evolutionary changes to control the
geometric progression of disease than others, for example, are escape mutants more
likely to occur, and to be evolutionary successful, in individuals who are vaccinated with
transmission blocking vaccines or replicating inhibiting vaccines. Furthermore, the
study reported that the live vaccines could promote reversion to the virulent strains of
the pathogen, mainly depending on multiple levels of natural selection, mechanism of
vaccine delivery, and epidemiological and surveillance methods for the study of the evo-
lutionary repercussions of vaccination. Gokbulut et al. (2021) demonstrated a mathemati-
cal model of COVID-19 with the effects of vaccine, discussed the ideas about the disease
to start decay or die out after vaccination process at the population level, and constructed
an SVI mathematical model considering foreign travelers and what kind of precautions
should be taken for the prevention of COVID-19 pandemic. The model presumed to vary
the percentage of vaccinated people in large populations. The findings suggested that
vaccination is substantially effective compared to wearing masks, maintaining social
distancing, and other preventive strategies used for the control of the disease. This chap-
ter described the herd immunity concept; the intervention of herd immunity is at the
heart of global vaccination efforts, when enough people in a population develop an
immune response, either through previous infection or through vaccination, so that the
virus can’t spread easily and even those who are not immune have protection. As per the
independent Bayesian evaluation test statistics (t = 1.36; b10=1405e−10; error 31.28%,
p = 0.085), approximately 31.28% of the population will acquire herd immunity and the
rest of the population would need to develop an immune response to the virus. The herd
effect might start to increase after the first wave of COVID-19, suggesting potential pro-
tection could be achieved sooner. Still, infectious disease experts eventually warn against
the notion of trying to reach herd immunity to the coronavirus without a vaccine. Moore
et al. (2021) studied the vaccination and non-pharmaceutical interventions for COVID-19
by mathematical modeling. In this study, a mathematical model was formulated consid-
ering the age of the population and different regions of the UK, which incorporated the
planned rollout of a two-dose vaccination program (dose administered 12 weeks apart,
protection onset 14 days after vaccination). Ekström et al. (2021) assumed a default vac-
cination uptake of 95% in those aged 80 years and older, 85% in those aged 50–79 years,
and 75% in those aged 18–49 years and then varied the considered uptake optimistically
and pessimistically. Further, vaccine efficacy against symptomatic disease was assumed
to be 80% on the basis of real data from Pfizer–BioNTech and Oxford vaccine AstraZeneca
being administered in the UK setup, and protection against infection varied from 0% to
85% (McLean, 1995). The combined interaction effect was studied by the model output
and also to extrapolate the reproduction number and pattern of daily deaths and hospital
admissions due to COVID-19. As per the sensitivity analysis, the default assumptions of
vaccine uptake by different age groups were 95%, 85%, and 75%, respectively. The sensi-
tivity analysis shows an optimistic scenario of increased uptake of 95%, 90%, and 85%,
whereas the pessimistic scenario with decreased uptake was 95%, 80%, and 70% in age
groups 80 years and older, 50–79 years, and 14–49 years, respectively (Li et al., 2020).
The study showed that vaccines that provide both high efficacy against disease and a
substantial amount of protection against infection offer a means of eventually relaxing
controls without a large subsequent wave of hospital admissions and mortality. An effec-
tive vaccine with high uptake is likely to be an essential element in the long-term control
and potential elimination of COVID-19. Jentsch et al. (2021) developed a mathematical
model by prioritizing COVID-19 vaccination for changing social and epidemiological
landscapes. The model was constructed based on how population shows adherence to
non-pharmaceutical interventions and responds to case incidence. In his model, school
and work places are also closed and reopened on the basis of reported cases. The formu-
lated model was completely parameterized with real data on COVID-19 pandemic cases
with induced mortality, SARS-Cov-2 seroprevalence, and population mobility, and the
demographic profile of the respondents was considered and also a vaccine efficacy of
75% was assumed against the disease and transmissibility. The model output shows that,
in the absence of vaccination 72,000 deaths (95% CI 40,000–122,000) will be expressed in
Ontario from January 1, 2021, to March 14, 2022, and when rate of vaccination has
increased, reach at (1.50%) of the population per week. In the absence of vaccination, the
contact-based strategy would reduce COVID-19 mortality by 92.6% on average at a vac-
cination rate of 1.50% of the population per week. However, the present study shows that
the average vaccination was 14.53% with SD 11.71 in the first dose and the mean incre-
mental change between the first dose and the second dose was 1.82% with SD 2.04.
Vaccination drive in India is not found to be statistically significant compared with gen-
eral population and hazard risk of disease and reproduction rate. At this stage (as of
April 26, 2021), the average expected vaccination coverage was 27.57% with SD 11.67. Kahn
et al. (2021) demonstrated a stochastic agent-based Susceptible Exposed Infection and
Recovered (SEIR) model of a nursing home to simulate SARS-Cov-2 transmission. The
model considered three scenarios varying environmental effect (VE) against infection,
infectiousness, and symptoms to understand the expected impact of vaccination in nurs-
ing homes, increasing staff vaccination coverage, and different screening strategies
under each scenario. The results showed that increasing the vaccination coverage in staff
decreases total symptomatic cases in each scenario. When there is low VE against infec-
tion and infectiousness, increasing staff coverage reduces symptomatic cases among resi-
dents. Encouraging staff vaccination not only is important for protecting them, but might
also reduce symptomatic cases in residents even if a vaccine confers at least some protec-
tion against the infection or infectiousness. Callaway (2021) showed that vaccination to
prevent COVID-19 has yielded excellent results with Pfizer announcing that their vaccine
has 95% efficacy. Marco-Franco et al. (2021) derived a mathematical model on COVID-19,
and their study concluded that the successive COVID-19 outbreaks could represent
between 7 and 12 million confirmed cases and over 4,000,000 deaths in Spain in 10 years.
Vaccination drive against SARS-Cov-2 is the only reasonable approach to control the dis-
ease, and it is clearly indicated from the research study, the risk of getting vaccinated
versus not getting vaccinated together with the vaccine data available (Lurie et al., 2020).
In case of Indian context, with the rapid outbreak of the second wave and with the emer-
gence of various mutant virus in different geographical region delta, there was great
uncertainty about the duration of immunity from a COVID-19 vaccine amid an acute
shortage, but there was some consensus that a two-dose vaccine could take a couple of
months. Those who have already taken the first dose of vaccination, the immunogenicity
will come down, and the experts indicate that the timely intervention of vaccination
would be done in a scheduled manner to reduce the infection rate and reproduction
number.
6.14 Conclusions
The present study (model output) concludes that our formulated model will help us to
study the various patterns of diseases and vaccination effects in association with different
characteristics by informing decisions about pandemic planning, identification of target
population, schedule of vaccination with varied population structure, resource allocation,
and implementation of prevention strategies to control rapid transmission of COVID-19.
In Indian context, mass vaccination is the only tool for the eradication of disease in addi-
tion to control measures such as maintaining social distancing, wearing masks, and strict
health policy implication at population level.
i. To explore vaccination priority order of who should receive the vaccine first, we
ranked each population by the ratio of the number of doses (I&II) administered to
the reduction in the outcome measure of interest.
ii. Scale up the vaccination program in selected clusters. In the interest of disease
control, the Government of India should frame the policy for public and make
it compulsory for all age groups. For each vaccination scenario considered, we
exhaustively tested the order of deployment among these groups (with an addi-
tional group of people with comorbidities independent of age).
Although too many existing vaccines are incepted at population level, vaccines are not
uniformly effective and the response may vary significantly due to factors including age,
comorbidity, food habits and clinical history. So, the concerned ministry should assess
the vaccination efficacy and side effects considering various clinical and demographic
attributes. In the case of a virus where the severity of symptoms is age dependent,
such as SARS-CoV-2, age-dependent vaccine efficacy may have a significant impact.
Of particular concern is whether an age-dependent decline in efficacy could alter the
group priority order for receiving a vaccine, and the potential scale of the subsequent
outbreak.
References
Anderson S.C., Edwards A.M., Yerlanov M., et al. Estimating the impact of Covid-19 control mea-
sures using a Bayesian model of physical distancing. medRxiv 2020; 4(2): 45–50.
Basavarajaiah D.M., Naraismhamurthy B. 2020. Advanced Designs of Experiment Approach to Clinical
and Medical Research. Singapore: Springer, pp. 77–131.
Bauch C.T. Limitation dynamics predict vaccinating behavior. Proc Biol Sci 2005; 272: 1669–1675.
Bubar K.M., Reinholt K., Kissler S.M., et al. Model-informed Covid-19 vaccine prioritization strate-
gies by age and serostatus. J Sci 2021; 371: 916–921.
Callaway E. COVID vaccine boosters: the most important questions. Nature 2021; 596: 178–180.
Castilho C., Gondim J.A., Marchesin M., Sabeti M. Assessing the efficiency of different control strate-
gies for the Covid-19 epidemic. EJDE 2020; 64: 1–17.
David H.A. 1981. Order Statistics, 2nd edn. New York: Wiley.
Dushoff J., Plotkin J.B., Viboud C. et al., Vaccinating to protect a vulnerable subpopulation. PLoS Med
2007; 4: 174–176.
Ekström AM, Berggren C, Tomson G. et al. The battle for COVID-19 vaccines highlights the need
for a new global governance mechanism. Nat Med 2021; 27: 739–740. doi:10.1038/s41591-021-
01288-8.
Gokbulut N., Kaymakamzade B., Sanlidag T., Hincal E. Mathematical modelling of Covid-19 with
the effect of vaccine. AIP Conf Proc 2021; 2325: 020065. doi: 10.1063/5.0040301.
Harrell F.E., Davis C.E. A new distribution-free quantile estimator Printed in Great Britain. Biometrika
1982; 63(3):635–640.
Hethcote H.W., Waltman P. Optimal vaccination schedules in a deterministic epidemic model. Math
Biosci 1973; 18(3): 365–381.
Jentsch P.C., Anand M., Bauch C.T. Prioritizing Covid-19 vaccination in changing social and epide-
miological landscapes; A mathematical modelling study. Lancet 2021; 3(5): 1–10.
Kahn R., Holmdahl I., Reddy S., Jernigan J., Mina M.J., Slayton R.B. Mathematical modeling to
inform vaccination strategies and testing approaches for Covid-19 in nursing homes. medRxiv
2021; 3(4): 33–38.
Khachatryan K.A., Narimanyan A.Z., Khachatryan A.K. Mathematical modelling of temporal spatial
spread of epidemics. Math Model Nat Phenom 2020; 15(6): 1–14.
Lao PDR. WHO guidelines (June report). 2020. https://www.who.int/laos
Li Q., Tang B., Bragazzi N.L., Xiao Y., Wu J. Modeling the impact of mass influenza vaccination
and public health interventions on Covid-19 epidemics with limited detection capability. Math
Biosci 2020; 325(7): 108378–108381.
Lurie N., Saville M., Hatchett R., Halton J. Developing Covid-19 vaccines at pandemic speed. N Engl
J Med 2020; 382: 1969–1973.
Marco Franco J.E., Pita-Barros P., González-de-Julián S., Sabat I., Vivas-Consuelo D. Simplified math-
ematical modelling of uncertainty: Cost-effectiveness of Covid-19 vaccines in Spain. J Math
2021; 9(56):90–96.
McLean A.R. Vaccination, evolution and changes in the efficacy of vaccines: a theoretical framework.
Proc Biol Sci 1995; 261 (1362): 389–393.
Moore S., Hill E.M., Tildesley M.J., Dyson L., Keeling M.J. Vaccination and non-pharmaceutical inter-
ventions for Covid-19: A mathematical modelling study. Lancet Infect Dis 2021; 21(6): 793–801.
Nuraini N., Khairudin K., Hadisoemarto P., Susanto H., Hasan A., Sumarti N. Mathematical models
for assessing vaccination scenarios in several provinces in Indonesia. BMJ 2020. MedRxiv pre-
print. doi: 10.1101/2020.12.21.20248241.
Saad Roy C.M., Wagner C.E., Baker R.E., et al. Immune life history, vaccination, and the dynamics of
SARS-CoV-2over the next 5 years. J Sci 2020; 370: 811–818.
Sergeev A., Khachatryan K. On the solvability of a class of nonlinear integral equations in the prob-
lem of a spread of an epidemic. Trans Moscow Math Soc 2019; 80: 95–111.
Verelst F., Willem L., Beutels P. Behavioral change models for infectious disease transmission: A sys-
tematic review (2010–2015). J R Soc Interface 2016; 13: 20160820.
Worldometer Section report published on February 18, 2020. https://www.worldometers.info/
coronavirus/
Zhou R., Li F., Chen F., Liu H., Zheng J., Lei C., Wu X. Viral dynamics in asymptomatic Patients with
Covid-19. Int J Infect Dis 2020; 96: 288–290.
7
Trend of COVID-19 Surge Projection
7.1 Introduction
SARS-Cov-2 is a scourge. As per the recent virtual Worldometer record, mortality now
exceeds 3.7 million, and as officially recorded by the WHO report, SARS-Cov-2 is fast
approaching and spreads across the world. Approximately 500 per million of the world
population will be infected in the first wave (Anderson et al., 2020a,b; Adolph et al., 2020;
Ainslie et al., 2020; Backer et al., 2020). The Centers for Disease Control and Prevention
(CDC, 2020) has projected the second wave. The SARS-Cov-2 variant is rapidly spread-
ing the infection and is well past its peak in Western Europe and North America, but it
is still in the range in Eastern Europe, South America, Turkey, and the Republic of India.
The second wave in India began in the period between the middle of February and March
2021. The positivity rate reached >65% in major cities and states such as Mumbai, Tamil
Nadu, Karnataka, Kerala, Uttar Pradesh, and Andhra Pradesh. However, the infection can
peak in the second and third weeks of May 2021 and the expected death toll can reach
up to 5.0% [CI 95% 1.5%–5.55%; CFR> 3.0%]. Almost half of the COVID deaths in India
to date have occurred during the 6 weeks ending June 6, 2021. Less incidence was seen in
February 2022. This period also accounted for about a quarter of the global and 90% of
the Asian SARS-Cov-2 deaths. Geometric disease progression has been started in the first
week period of pandemic when deaths per millions in India exceeded those in Western
Europe and North America, including the USA. India’s second wave nevertheless appears
to have peaked around May 23, 2021 at a 7-day daily average death rate of 4,191, making it
3.6 times as lethal as the country’s first wave, which peaked at 1,166 deaths on September
15, 2020. Many studies projected the third wave of COVID-19 pandemic, and the disease hit
many countries because of the lack of behavioral vaccination and deviation of health policy
( )
due to genetic mutant variants of SARS-Cov-2. India’s delta plus δ + variant has become
a concern for an anticipated third wave. As per the presumed hypothetical study, India
has barely put behind the horrors of the 2nd wave of COVID-19 pandemic. Maharashtra
has made the red signal to alert for the third wave (as data sets has used June 24, 2021,
17 delta plus cases were found). The delta (δ ) mutant variant of SARS-Cov-2 is respon-
sible for the peak of the second wave of the COVID-19. Recently, the Indian Council of
( )
Medical Research (ICMR) reported that the delta plus δ + variant has been detected even
though it has not been classified as a variant of concern (VOC) (Yadav et al., 2021). The
( )
delta plus δ + variant was first detected in Europe during March 2021. It has been isolated
( )
in some samples in India and around ten other countries. The delta plus δ + is a new
( )
version of its mutant variants. It is, however, not known whether the δ + variant is more
DOI: 10.1201/9781003204794-7 217

infectious or fatal compared with the delta variant (Backer et al., 2020; Boulware et al., 2020;
Bar-Zeev et al., 2020; Bjørnstad et al., 2020a; Barzilai et al., 2007). The delta variant has been
found to be deadlier and capable of causing more severe complications, leading to a higher
rate of hospitalization of patients. Different COVID mutant variants spread geographically
around the world, which are presented in Table 7.1.
The GRBC (2021) study found B.1.617.2 variant, now known as delta variant, to be widely
prevalent in the Gujarat state in India in the second wave, and the variant had two amino
acids (Arg158 and Phe157/dd) missing, while E156G got mutated on the spike protein
of the virus. These changes in the variant helped it escape the antibodies as it did not
match the copy of the original virus they had in memory. Researchers advocate regular
genome sequencing of viruses to check its transmission, virulence and altered antige-
nicity. However, experts conclude the immune escape has not been widely reported yet.
The cases of severe infections are still low. According to a latest report by Public Health
England, a UK Government public health body, 63 genomes of delta with K417A mutation
have been identified on GIASAID. In its latest updated report on SARS-Cov-2, India has
reported six cases of AY.1 or delta plus as of June 7, 2021. However, scientists fear monoclo-
nal antibody cocktail therapy may not work against the delta plus mutant. At this point,
the variant frequency for K417N is not much in India, say experts. In an earlier report,
PHE said that the delta AY.1 (delta with K417N) was found through routine scanning for
variation in delta. The delta mutant genetic variant is reported in 85 countries. However,
the research evidence suggests that two doses of immunization reduced hospitalization
by 92%–96%. Protection from symptomatic disease was reduced by 17% for delta com-
pared to alpha with a single dose of vaccine. Modest reduction in effectiveness against
symptomatic disease was noted (Cobey, 2020; Chu et al., 2020; Cairoli et al., 2021). The
spread of delta variant has helped in getting people vaccinated with two doses a major
health policy goal, and these support that. However, the first dose appears to provide
substantial protection from severe illness requiring hospitalization. Currently, we see
regional variation of surge of SARS-Cov-2 in India. The data reveal that the second wave
TABLE 7.1
SARS-Cov-2 Variants by World Health Organization (WHO)
WHO label Lineage Variant Class First Detected Samples
Alpha (α) B.1.1.7 VOC The UK, September 2020
Beta (β) B.1.351 VOC South Africa, May 2020
Gamma (γ) P.1 VOC Brazil, November 2020
Delta (δ ) B.1.617.2 VOC India, October 2020
Epsilon (ε) B.1.427, B.1.429 VOI The USA, March 2020
Zeta(ζ) P.2 VOI Brazil, April 2020
Eta (η) B.1.525 VOI Several countries, December 2020
Theta(θ) P.3 VOI Philippines, January 2021
Iota (ι) B.1.526 VOI The USA, November 2020
Kappa (κ) B.1.617.1 VOI India, October 2020
Delta (δ + ) B.1.617.2.1 (AY.10) Characterized by Mumbai, India—highly transmissive
the acquisition of
K417N mutation;
non-VOC
Source of data: WHO weekly report, 2021; VOC—variant of common; VOI—variant of interest.
COVID-19 Surge Projection 219
is more than twice as deadly as the first wave. The average six-weekly global mortality
during the first wave period from March 6 to October 21, 2020, was 29 per million, and
it was 68 during the second wave period between October 21, 2020, and June 6, 2021. The
higher mortality in the second wave coincides with the different patterns of the Spanish
flu a century ago. In the urge of disease prediction, mathematical and statistical simu-
lation is very important to explore new interventions of the disease phase in different
time periods. The literature survey clearly depicted that earlier published mathematical
models in various journals have projected inaccurate projection of the disease impact
due to insufficient consideration of various clinical and biological attributes. Despite
several models existing around, many remain imponderable, such as vaccine availability
in places where these are most needed, the effect of new mutant and possibility to fore-
cast third and fourth waves. The Reuters research group conducted an opinion survey
of 40 healthcare specialists, doctors, scientists, virologists, epidemiologists, and profes-
sors from around the world, from which it gathered that the third wave would hit the
country between October 2021 and January 2022. The wave will be controlled better as
many people will be vaccinated by then, and the number of cases will be much less than
what India witnessed in the second wave. Many public media broadcasted the news and
information pertaining to the third wave—the surge of third wave will highly affect
children more than adults. Many studies are cited worldwide on COVID seroprevalence,
in India, the (ICMR) Indian Council of Medical Research has proved by the seropreva-
lence study done on selected clusters of Indian states considered with a sample of 10,000
adults and children population. As per the study results, the SARS-Cov-19 seropreva-
lence in the age group below 18 years was 55.57% and that in the age group above 18
years was 63.5%. The above research findings clearly depicted that children will not be
disproportionately affected in the third wave surge as it was projected because they also
have the same level of antibody. Overall, a large number of people have developed resis-
tance against SARS-Cov-19. Besides all findings of the research, India has drastically
increased its vaccination drive in high, medium, and low prevalence states and union
territories. Arbitrarily, the effect of SARS-Cov-19 will be less in Indian states due to the
strict practice of prevention strategies and behavioral vaccination (Cohen and Shoenfeld,
1995; Ehrenfeld et al., 2020; Fine et al., 2011). For the sake of health policy intervention,
accurate estimation of different surges of SARS-Cov-19 is very essential to implement
the health policy at population level. In this above paradigm, statistical modeling is very
important for projecting the surge of SARS-Cov-2 third wave by real probability with
highest credibility of the statistical values (Kucharski et al., 2020; Leung et al., 2020b).
An earlier analytical method has predicted the surge of third wave by using frequentist
approach, and all constructed models are patrimonial. They had some shortfalls in pro-
viding accurate estimation (Flaxman et al., 2020; IHME, 2021; Jamilloux et al., 2020). In
this rationality of analytical research gap, we developed a new model by superimposing
both Bayesian and frequentist approaches without substantial loss of information of the
attributes. Our newly demonstrated model will be able to predict the likelihoods and
real probability values and to also estimate the waves of the disease for the future course
of action. This prediction dynamics model will help us to navigate the third wave; it can
also be useful to public health planners of the policy to implement health policy; and it
will support the allocation of healthcare resources and will help us to be prepared and
monitor the various policy interventions. In this present research, we describe a new
approach that forecasts the real probability of projectile cases of SARS-Cov-2 in the near
future given the past occurrences using a large number of salient assumptions that were
drawn using real data sets.
The data sets of different attributes were collected from the government authorities, and
the available information was collected from the virtual platform. The collected data series
were grouped into the various following attributes (Table 7.2).
By the use of above-said attributes ( A1 , A2 , A3 … Ai ), we formulated the Bayesian classi-
fier model to extract the real probability.
 Cj  A 
( )
Conditional probability P   = P Ai , C j P( A); P  i  = P ( Ai , Ci ) P C j
 Ai   C
( ) (7.1)
As per Bayes theorem, we consider each attribute and class label as random variables of
COVID attributes ( A1 , A2 , A3 … Ai ). Our goal is to predict the real probability of different
traits.
( )
P c j /Ai =
( )
P ( A1 , A2 , A3 … Ai / C ) P c j
(7.2)
P ( A1 , A2 , A3 … Ai )
TABLE 7.2
Different Attributes of SARS-Cov-2 Considered for Model Construction
S. No. Attributes S. No. Attributes
A1 Total population of the country A10 Latent period of the first and second waves
likely to be infected projected for the third wave by using
weighted average infection
A2 Proportion of susceptible A11 Average death rate of the first and second
population to be infected in 1 year waves by using secondary data to project
of infection inception the third wave deaths
A3 Number of population to be A12 Total number of population to suffered
infected in the first wave from opportunistic infections (OIs) such as
black fungus and white fungus—projected
for the third wave
A4 Number of treated population in A13 Proportion of population susceptible to OIs
the first wave in the first and second waves
A6 Number of population relapsed A14 Total number of mutant variants likely to
COVID in the first and second emerge and affect in the third wave
waves
A7 Total number of population in the A16 Total number of population migrated from
age group <18 years to be infected the abroad to spread the disease
in the third wave
A8 Number of population vaccinated A17 Ritual conference and election campaign
to prevent disease spread likely to lead to the surge of the second
wave
A9 Number of population A18 Number of patients infected in the age
unvaccinated to transmit the group <18 years from their family
infection members
A19 Number of patients died in the age group
<18 years
(
Choose the value of ci that maximizes P A1 , A2 , A3 … Ai / C j . )
( ) ( ) ( ) (
P A1 , A2 , A3 … Ai /C j = P A1 /C j P A2 /C j P A1 /C j … P Ain /C jk ) ( ) (7.3)
nk
(
P A1 , A2 , A3 … Ai /C j = ) ∑P ( A /C
i=1
in jk ) (7.4)
If one of the conditional probabilities is zero, then the entire expression becomes zero. The
probability of estimation of real probability with different attributes is as follows:
N ic
Original P A1 /C j =( ) Nc
N ic + 1
(
Laplace P A1 /C j = ) Nc + c
N ic + mp
M − estimates P A1 /C j =( ) Nc + m
where c = the number of jth classes, P = prior probability, and m = parameters.

Due to certain limitations of naive Bayesian classifier, such as lack of judicial limits, non-
existence of likelihoods, and being unable to estimate the credibility by using desirable
precision on selected parameters, again we formulated and adopted a new intervention
model of weighted regression model for testing the real probability based on the observed
probability values by assigning the score or index value “i” with data series of SARS-Cov-2.
7.3 Bayes Weighted Regression Model

We consider random variables ( x1 , x2 , x3 … xn ) with likelihood parameters (θ 1 , θ 2 …θ k ). All
random variables are normally distributed with mean µ and variance σ 2; N ~ µ , σ 2 . All ( )
observations are independent and identically distributed (i.i.d.) (normalcy). Each assigned
rank converges with mean value theorem (MVT), and then the model becomes
jk  
f ( xnθ k ) ∑  Wi xn * I  (7.5)

∑ 
A
i=1  Wi 
where
Wi = the weightsassigned to rv;
xn = random variables at nth observation;
θ k = likelihood estimation parameter at kth parameter;
I A = index score of different attribute variables of p-real value.
We employed the above model to estimate the likelihood function of each selected variable
by frequentist approach by the selection of dependent variable Yi and independent vari-
ables Xi. Let us consider that the dependent variable is the average infection rate of each
month and the independent variable is I A value. The linear regression fixed model was
employed for the estimation of likelihoods of each selected attribute of COVID.
y i = f ( xi , β )θ k + ei (7.6)
where y i is the dependent variable, f is the function, xi is the independent variable, β is

the unknown parameter or regression coefficient, θ k MLE (maxium likelihood estimation)
“s” of selected kth parameter, and ei is the error components from equation (7.6). We will
construct the multiple logistic regression.
(
y ij = f xij , β 0 , β1 , β 2 …β n θ k + eij ) (7.7)
where β 0 , β1 , β 2 …β n are the unknown parameters or regression coefficients of selected

variables or attributes.
Equation (7.7) becomes
y ij = a + β 0 X 0 + β1 x1 + β 2 x2 + …β n xn + eij (7.8)
∑ ( x − x )( y − y )
Sxy
b1 = Where Sxy = i i
Sxx i=1
Sxx = ∑( x − x ) b
i=1
i
2
0 = y − b1 x
yij = a + β0 X
0 + β1 x1 + β2 x2 + βn xn + eij (7.9)
The total variation was determined by the coefficient of variation
∑ ( y − y )
n 2
i ij
R (% ) =
2 i=1
(7.10)
∑ (y − y )
n
i ij
i=1
n
1
∑( y − y )
2
Mean squareerror ( MSE ) = i ij (7.11)
n i=1
ConfidenceInterval CI ( 95% ) = X ± 1.96SE (7.12)

We can estimate the likelihood function of various attributes.
L ( λn / θ k ) = n
i=1 πf ( xi )
n
L( λ n / θ k ) = i = 1 πλ e −θ k
n
−λ ∑θ
= λ ne i=1
(7.13)
We can construct logistic regression to extrapolate the relation between various attributes
at time “t” of COVID infection.
1
yt = β 0X 0 + β1x1 + β 2 x2 +…β n xn
(7.14)
1+ e
 p 
 1 − p  = exp ( β 0 X 0 + β1 x1 + β 2 x2 +  β n xn )
 p 
ln  = β 0 X 0 + β1 x1 + β 2 x2 + …β n xn
 1 − p 
There are several analogies between linear regression and logistic regression. LR uses the
estimates of the maximum likelihood function.
( ) XT (y − µ)
−1
β 1 = β 0 + X T WX
where β = the vector of logistic regression; W = the square matrix of order “N” with ele-
ment ni π i ( 1 − π i ) on the diagonal and zero everywhere else; and µ is the vector of length
“N” with element µi − ni π i .
∑
n
( y i − pi )
2
Error pseudo ( R ) = 1 − 2 i=1
∑
n
i=1
( y i − y )2
In the logistic regression model, the value of classifier lies between 0 and 1, i.e., 0 ≤ h ( x ) ≤ 1,
so we can estimate the hypothesis. We also find the logistic function h ( x ).
h ( x ) = g θ T kx ( ) (7.15)
1
=> g ( z ) = (7.16)
1 + e −θ kx
 x01 
  1
x =  x 11  h ( x ) = 1 + e −θ kx (7.17)
 . 
 .

 xni 
So, for outcomes y i = 1 where i = 1, 2, 3 n
1
P ( y i = 1/ xinθ ) = hθ ( x ) = T (7.18)
1 + e −θ kx
θ kx = β 0 X 0 + β1 x1 + β 2 x2 + …β n xn
 for y i = 1; hθ ( x )

So, 
 for y i = 0; 1 − hθ ( x )
P ( y i ) = hθ ( x ) 1 − hθ ( x ) i 
1− y
P ( y i ) is the likelihood of COVID attributes for various data points.
P ( X i /Yi ) = ∑p ( x y )
i=1
i i (7.19)
P ( X i /Yi ) = L ( xi ) = ∑p ( x ) (1 − p ( x ))
i=1
i i
In case of logistic regression, we will get
1
P (Yi = 1/X iθ ) = hθ ( x ) = T (7.20)
1 + e −θ kx
n n
P ( X i /Yi ) = L ( xi ) = ∑p ( x /y ) = ∑h ( x)
i=1
i i
i=1
θ
yi
1 − hθ ( x )1− yi 
  (7.21)
θ T x = θ 0 + θ 1 x1 + θ 2 x2 …θ n xn
θ
T
x = θ 0 x0′ + θ 1 x1′ + θ 2 x2′ …θ n xn′
 p 
L (θ ) = ln 
 1 − p 
L (θ ) = log p ( x / y )
L (θ ) = log p ( x/y ) = ∑h ( x)
i=1
θ
y i′ 1 − h ( x )1− yi′ 

θ

(7.22)
MLE ′s = P ( x/y ) = ∑  y log h ( x ) + (1 − y ) log(1 − h ( x )

i=1
i θ i i θ i (7.23)
From the above new intervention of analytical procedure, we will predict the real prob-
ability and likelihood estimation of real probability and credibility by Bayesian classifier
by likelihoods which is estimated by the frequentist approach. It is very easy to explore
the dynamics of new SARS-Cov-2 infections during the current COVID-19 and on surge
of various waves predicted at global platform. The modeling is critical for public health
planning and efficient healthcare allocation and for monitoring the effects of policy inter-
ventions. This model can support the projection of different waves using both approaches
(Liang et al., 2020; Lauer et al., 2020; McBryde et al., 2020; Miller et al., 2020). This research
will describe a new approach that forecasts the number of surges or waves in the near
future given past occurrences using various numbers of assumptions that are correlated
with clinical, epidemiological, genetic, and environmental approaches. Different attributes
were collected from various national health authorities (A1 to A19 shown in Table 7.2). The
model was formulated based on real structured and unstructured data sets. The positivity
data of Indian states were considered; if the positivity is <5%, it is coded as “0” and if it
is >5%–10%, it is coded as “1”. Simultaneously, weighted ranks were assigned to the high
prevalence states and union territories based on the total positivity of the first and second
waves. We determined the prior and posterior probabilities on each individual attribute by
using the Bayesian classifier method (R statistical software was used for data compilation);
again, Bayesian real probability is superimposed with the frequentist approach using the
following formula (Table 7.3):
IA =
∑X w ∗ p
n i
(7.24)
∑w
ij
i
where
I A = index value of different attributes of SARS-Cov-2;
X n = random variables of x1,x2,x3…xn (xn = disease percent positivity rate at nth state or
UT);
wi = weights assigned to individual state based on positivity, I and II wave prevalence;
pij = prior and posterior probabilities of ith attribute at jth region or state.
TABLE 7.3
Formation of Data Sets for Superimposition of the Model to Frequentist Approach
Real
Attributed
P-Value IA =
∑X w n i
* pij
Secondary
Data (Monthly Average Infection
Weights
Assigned
Obtained From
Bayesian ∑w i
or Weekly) Rate (%); ( xn ) Attributes (Ai) to r.v. Classifier

January 2020 X11 (A1,A2…Ai1) Wi1 P1…1j IA1
February 2020 X12 (A1,A2…Ai2) Wi1 P12…2j IA2
March 2020 X13 (A1,A2…Ai3) Wi1 P13…3j IA3
April 2020 X14 (A1,A2…Ai4) Wi1 P14…4j IA4
May 2020 X15 (A1,A2…Ai5) Wi1 P15…5j IA5
June 2020 X16 (A1,A2…Ai6) Wi1 P16…6j IA6
July 2020 X17 (A1,A2…Ai7) Wi1 P17…7j IA7
August 2020 X18 (A1,A2…Ai8) Wi1 P18…8j IA8
September 2020 X19 (A1,A2…Ai9) Wi1 P19…9j IA9
October 2020 X20 (A1,A2…Ai10) Wi1 P12…10j IA10
November 2020 X21 (A1,A2…Ai11) Wi1 P13…11j IA11
December 2020 X22 (A1,A2…Ai12) Wi1 P12…12j IA1
February 2021 X24 (A1,A2…Ai14) Wi1 P14…14j IA13
March 2021 X25 (A1,A2…Ai15) Wi1 P15…15j IA14
April 2021 X26 (A1,A2…Ai16) Wi1 P16…16j IA15
May 2021 X27 (A1,A2…Ai17) Wi1 P17…17j IA16
∑x n ∑ (A , A A )
1 2 ij ∑W i ∑p ij ∑I A
7.4 Model Results
The Bayesian classifier was employed to extract the prior and posterior probability values;
usually, the probability values were predicted based on attribute (class) membership, such
as the probability that a given tuple belongs to a particular attribute (Table 7.4). The present
study comparing classification algorithms has found a simple naive Bayesian classifier that
was employed to draw the decision-making process with high accuracy and speed applied
massive attributed data sets. During the analysis of naive Bayes classifier, we assumed that
the effect of an attribute value on a given class is independent of the values of the other
attributes. This assumption was class conditional independence. Further, we diagnosti-
cally check the classifier performance by using sensitivity analysis.
TP + TN FP + FN
Accuracy = , Errorrate ( misclassification rate ) =
P+N P+N
TP TN TP +
Sensitivity ( TPR, recall ) = , Specificity ( TNR ) = ; Precision = ,
P N TP + FP
FScore =
2 * precision * recall
; Fβ where β is nonnegativereal number = 2
(
1 + β 2 * recall )
precision + recall β * precision + recall
TABLE 7.4
Prior and Posterior Probability Values of Different SARS-Cov-2 Attributes
Prior Posterior
S. No. Attributes Distribution Distribution
A1 Total population of the country likely to be infected 0.964 0.035
A2 Proportion of susceptible population to be infected in 0.84 0.16
1 year of infection inception
A3 Number of population to be infected in the first wave 0.76 0.24
A4 Number of treated population in the first wave 0.62 0.38
A6 Number of population relapsed COVID in the first 0.11 0.89
and second waves
A7 Total number of population in the age group <18 0.24 0.76
years to be infected in the third wave
A8 Number of population vaccinated to prevent disease 0.36 0.64
spread
A9 Number of population unvaccinated to transmit the 0.41 0.59
infection
A10 Latent period of the first and second waves projected 0.36 0.64
for the third wave by using weighted average
infection
A11 Average death rate of the first and second waves by 0.014 0.99
using secondary data to project the third wave
deaths
A12 Total number of population to be suffered from 0.66 0.34
opportunistic infections (OIs) such as black fungus
and white fungus—projected for the third wave
A13 Proportion of population susceptible to OIs in the 0.17 0.83
first and second waves
A14 Total number of mutant variants likely to emerge and 0.68 0.32
affect in the third wave
A16 Total number of population migrated from the 0.91 0.09
abroad to spread the disease
A17 Ritual conference and election campaign likely to 0.77 0.23
lead to the surge of the 2nd wave
A18 Number of patients infected in the age group <18 0.16 0.84
years from their family members
A19 Number of patients died in the age group <18 years 0.03 0.97
Mean sensitivity (%) = 0.56; mean specificity = 0.92; AUC mean = 0.88; recall mean = 0.94 (74%); precision = 0.873;
F1-score = 0.99 (1.0); accuracy = 0.93; pseudo-R2 (%) = 0.913.
From the naive Bayes extraction, prior and posterior probability values were determined
with varying conditional probability values. The massive attributed data sets of SARS-
Cov-19 were used to extrapolate the real probability values. Table 7.5 depicts that the
attributes range from A11 to A19. As per the analysis, we noticed that on prior (96.4%; pos-
terior = 0.964) total population of the country was already likely to be infected for herd
immunity; 84% proportion of susceptible population to be infected in 1 year of inception of
infection; 76% population was infected in the first wave; 62% population was treated in the
first wave; 11% population were infected by COVID in the first and second waves; 24% of
<18 years of age group population were likely to be infected in the third wave projections;
only 36% Indian population received single dose vaccination; 41% unvaccinated popula-
tion likely to be transmitting the infection in the third wave. The mean latent period from
TABLE 7.5
Test Results of Accuracy
Algorithm Precision Recall (%) Accuracy (%) AUC
Classification tree 85.63% 94.06 93.74 0.88
Naive Bayes 83.47% 93.11 88.12 0.91
k-NN 80.13 87.34 78.16 0.83
the first wave to the second wave was 45.55 days with SD 1.93 days (determined based on
weighted mean of all states). An average death rate of 1.4% was recorded in the first wave,
and in the case of second wave COVID death rate was (CI 95% 2.5%–4.56%) at the posterior
probability of 99.0%; 34% population is expected to be exposed to opportunistic infections
(OIs) such as black fungus and white fungus (Opportunistic infection)—projection for the
third wave; 17% of total infected population is susceptible to OIs in the first and second
waves; 32% expected rate of mutant variants likely to be less affected in the third wave;
91% population migrated from abroad to spread the disease in the first wave; 77% ritual
conference and election campaign has increased the surge of the second wave in India;
16% patients infected in the age group <18 years from their family members; and 0.03%
children died in the age group <18 years in the first and second waves of SARS-Cov-19.
Based on the model output (Table 7.4), it can be seen that the level of accuracy using the
naive Bayes algorithms was 88.12% [recall 93.11%; AUC 0.91] with the number of true pre-
dictions being 963 data sets out of the total amount of data sets tested (1196). The results of
the performance accuracy values for the three algorithms are presented in Table 7.5. In case
of classification tree, the precision was 85.63%, the recall was 94.06%; and the accuracy was
93.74% with AUC 0.88, and a similar approach was correlated in the k-NN model [precision
80.13%, recall 87.34%, accuracy 78.16%, AUC 0.83]. It was found that the naive Bayes is the
best robust model for comparing massive attributes of SARS-Cov-19. The Beysian classifier
of COVID attributes has diagnostically checked by the formulated model, the accuracy
was measured based different measurements. It is defined as the number of data records
correctly classified by an algorithm after testing the classification results and is expressed
in percentage (accuracy is defined as the level of closeness between the predicted value
and the actual value).
The secondary weekly district-wise SARS-Cov-19 positivity rates were obtained from
MoHFW, Government of India (< 5% to > 10%, both positivity rates were included for model
construction). Table 7.6 shows the analytical procedure for the determination of index score
based on the real data sets of positivity rate (expressed in percentage). The following proce-
dure was used to calculate IA, and each concerned positivity rate of data sets was assigned
ranks or weights based on the proportion of population infected in the I wave. Clinical
attributes and containment history were used for assigning ranks or weights ( wn ). In the
next step, the assigned ranks or weights were multiplied with positivity rate, Xn * Wn/Wn.
Finally, the IA score was determined by multiplying weighted average and pij —prior and


posterior probabilities of ith attributes at jth region or state  I A =
∑ X n wi 

* pij  . Further,

 ∑ wi 

we code COVID positivity rate <5% as 0 and that >10% as 1. Various attributes from A1 to
A19 including IA were considered as independent variables. The data sets of dependent
variables and independent variables were modeled by logistic regression smoothing tech-
niques of Monte Carlo simulation bootstrap method. The coefficients and likelihoods of
TABLE 7.6
Weekly district-wise mean positivity rates in end of June 2021 (>= 5% to < 10%)
State/UT Positivity (%) Weights or Ranks Mean Values of Weights Bayesian P-Value (Pij)
∑X wn i
IA = ∗ pij
∑w i
(X n) (Wn) X n * Wn X n*Wn /Wn Posterior Prior
Himachal Pradesh 5.11 2 5.11 0.438 0.14 0.86 0.061
Tamil Nadu 5.24 3 10.48 0.897 0.22 0.78 0.197
COVID-19 Surge Projection
Karnataka 5.97 4 17.91 1.533 0.28 0.72 0.429

Goa 6.16 5 24.64 2.110 0.33 0.67 0.696
Haryana 6.46 6 32.3 2.765 0.41 0.59 1.134
West Bengal 6.57 6 39.42 3.375 0.42 0.58 1.418
Arunachal Pradesh 6.71 7 46.97 4.021 0.5 0.5 2.011
Jammu and Kashmir 6.77 8 54.16 4.637 0.55 0.45 2.550
Puducherry 6.97 9 62.73 5.371 0.52 0.48 2.793
Jharkhand 7.00 10.5 73.5 6.293 0.58 0.42 3.650
Tripura 7.00 10.5 73.5 6.293 0.52 0.48 3.272
Rajasthan 7.42 12 89.04 7.623 0.6 0.4 4.574
Odisha 7.45 13 96.85 8.292 0.63 0.37 5.224
Nagaland 7.51 14 105.14 9.002 0.66 0.34 5.941
Mizoram 7.58 15 113.7 9.735 0.64 0.36 6.230
Assam 7.6 16 121.6 10.411 0.65 0.35 6.767
Manipur 7.66 17 130.22 11.149 0.76 0.24 8.473
Maharashtra 7.69 18 138.42 11.851 0.72 0.28 8.533
Meghalaya 7.86 19 149.34 12.786 0.73 0.27 9.334
Sikkim 8.33 20 166.6 14.264 0.73 0.27 10.413
Andhra Pradesh 8.36 21 175.56 15.031 0.77 0.23 11.574
Kerala 9.2 22 202.4 17.329 0.82 0.18 14.210
Mean 7.12 11.68 88.79 7.60 0.55 0.45 5.01
SD 0.98 6.27 55.77 4.77 0.19 0.19 4.03
Note: Bayesian P-values (Pij) were extracted based on various attributes and real data sets by using Bayesian classifier; IA is the index value of attributes
229
determined from real data.

attributes were extracted from the model. We tested the hypothetical statement at 1% level
of significance.
Table 7.7 shows that in the prediction of surge of third wave, by using frequentist and
Bayesian approaches, dependent variables and independent variables were considered.
TABLE 7.7
Prediction of Surge of the this wave by Using Frequentist and Bayesian Approaches—India
Variable Coefficient Se P-Value Odds Ratio
Total population of the country likely to be 17.29 42,105.76 ≤0.01 >100
infected
Proportion of susceptible population to be 1.67 4,601.94 ≤0.01 5.30
infected in one year of infection inception
Maximum number of population to be 1.63 13,334.17 ≤0.01 5.09
infected in the first and second waves
Number of treated population in the first 2.62 28,164.67 ≤0.01 13.77
and second waves
Number of population relapsed COVID in 0.02 5,726.71 ≥0.01 <1.0
the first and second waves
Total number of population in the age group −97.69 12.3 ≥0.01 <1.0
<18 years likely to be infected in the third
wave
Number of population vaccinated to prevent 16.28 0.236 ≤0.01 25.22
disease spread
Number of population unvaccinated to 1.74 0.803 ≤0.01 8.55
transmit the infection
Latent period of the first and second waves 0.89 0.124 ≥0.01 <1.0
projected for the third wave by using
weighted average positivity infection
Total Number of population unvaccinated to 13.55 0.792 ≥0.01 4.88
transmit the infection
Total number of population to be suffered 22.0 2.67 ≤0.01 9.03
from opportunistic infections (OIs) such as
black fungus and white fungus—projected
for the third wave
Proportion of population susceptible to OIs 31.37 5.5 ≤0.01 >100
in the first and 2nd waves
Total number of mutant variants likely to 279.59 24.36 ≤0.01 2.66
emerge and affect in the third wave
Total number of population migrated from 240.02 78.360 ≤0.01 18.55
the abroad to spread the disease
Ritual conference and election campaign 10.96 0.309 ≤0.01 28.47
likely to lead to the surge of the 2nd wave
Number of patients infected in the age group 3.89 38,958.46 ≤0.01 48.85
<18 years from their family members
Number of patients died in the age group 175.28 3,704.17 ≥0.01 <1
<18 years
Projectivity of the 3rd wave based on −29.43 1.38 ≥0.01 <1
secondary data of SARS-Cov-2—India (first
and second waves)
Percent positivity (<5% coded as 0; >5%–10% −635.69 5.67 - <1
coded as 1)
Chi-square −25.78; df 19.
The Bayesian IA score was superimposed with that of frequentist approach. Logistic
regression was employed to estimate the surge of SARS-Cov-19. As per the model results
or research findings, the number of people infected by COVID in the first and second
waves (odds) because for exposed in the crowded places. The latent period of the first and
second waves projected for the third wave by using weighted average positivity infection
odds ratio shows <1, these projective variables were not found to be statistically significant
[CI 99% 0.21–0.33] with the surge of third wave estimation; the proportion of population
unvaccinated to transmit the infection strongly correlated to spread the infection [odds
8.55, p < 0.01] after the 3–8 months surge of the second wave, but it shows that the human
population will be least affected because of effective vaccination coverage, herd immunity
(odds > 100) and strict policy guidelines framed by the government. In case of the second
wave of SARS-Cov-19, 78.0% population migrated from abroad to spread the disease by
various genetic mutant variants and also 45% migrant population has not received vac-
cination and not followed the prevention strategies and 80% deviated from the COVID
policy guidelines. In addition to that a combination of a large asymptomatic population
and the presence of more infectious variants of the virus during the second wave made
it much steeper than the first wave that reached the peak in the months of April and May
2021, and it will continue to transmit the virus even to those who did not get behavioral
vaccination (preventive measures like wearing masks, sanitation and avoid unnecessary
exposure to public places). For instance, the UK genetic mutant strains were detected and
affected a significant proportion of population [odds 15.63; CI 95% 5.52–20.63], especially
elderly population with one or more underlying comorbid conditions (coefficient 76.22),
and the positivity rate would be 65%–76.22% in the month of May 2021. There will be
50% higher transmission according to the US Centers for Disease Control and Prevention
(CDC). The genetic mutant virus strain B.1.671 has significantly affected the major cities
of India. The projectivity of the third wave based on the secondary data of SARS-Cov-2
India (first and second waves) from superimposed method of Bayesian and frequentist
approach (discussed above). The impact of the wave was significantly less in India because
of the effective vaccination drive, herd immunity, genetic complexity, and strict policy
guidelines [coefficient −29.43, with SE 1.30, P > 0.01, odds <1.0]. In case if the disease or the
third wave will be incepted at population level, the percent positivity rate would not cross
5.6%–16.75% [CI 99% 3.15%–16.75%].
7.4.1 Projective Model of the Third Wave by Using IA Score

The simple regression model was employed to forecast the projectile point of the third
wave in Indian context. The percent positivity rate of all states was considered (June 2021
week 3 mean positivity rate) as the dependent variable, and IA score of SARS-Cov-19 was
considered as the independent variable. The model was demonstrated by R statistical
software. As per the model results, the dependent and independent variables moved in a
straight line and the regression line is ŷ = 3.87982X -22.64536, which means infection posi-
tivity rate would be 3.87% with a maximum steepest IA score of 22.64. The model inputs are
represented graphically in Figure 7.1.
7.4.2 Calculation Summary
Sum of X = 156.62, Sum of Y = 109.46, Mean X = 7.1191
Mean Y = 4.9755; Sum of squares (SSX) = 20.1838; Sum of products (SP) = 78.3095
Regression equation = ŷ = bX + a
FIGURE 7.1
Predicted positivity rate of the thirdwave (less impact in India).
b = SP/SSX = 78.31/20.18 = 3.87982; a = MY − bMX = 4.98 − (3.88*7.12) = 22.64536

ŷ = 3.87982X − 22.64536.
7.5 Discussion
The present study demonstrated the real data sets of SARS-Cov-19 to predict the possibil-
ity of the third wave in India context. The output of the model clearly forecasts the dispro-
portionately uncorrelated positivity rate, the general population was the least affected
because the population (IQR 35–55%) had already acquired herd immunity, and vaccina-
tion coverage had increased in the elderly population. Many studies in the literature sug-
gest that in individuals who get one or two doses of vaccination, the infection rate was
found to be uncorrelated (Nishiura et al., 2020; Ngonghala et al., 2020; Read et al., 2020).
WHO and ICMR conducted a research study on the seroprevalence of both adult and chil-
dren population in select districts (cluster purposive sampling) of five states with a sample
size of 10,000. The results of the study were significantly different in children and adult
population; the prevalence rate is more in adults (63.5%) as compared to children (55.7%).
Children will not be disproportionately affected in the third wave as it was projected
because they also have the same level of antibody. Overall, a large number of people have
developed resistance against SARS-Cov-19 because of the genetic complexity and HLA
type. The expert panel of COVID clearly emphasized that the impact of third wave depends
on whether the virus and its variants are getting rid of any scope to infect people. There
will be a variant. But there is no new way to fight any new variant. Further, health policy
interventions should reduce the possibility of next wave. Many preventive measures have
been initiated at population level (despite the unlocking process, social distancing and
other appropriate behaviors are followed). Researchers have opined that the timing of the
possible wave can’t be predicted. The projected wave will be controlled better as many
people will be vaccinated. The present model-based study describes how the third wave is
not correlated with the existing positivity rate considering many clinical, social, and
related attributes presented in the results part. A lesser infectivity triggers the third wave
of SARS-Cov-19, and even more variants will emerge. A recent study done by Imperial
College London and ICMR concluded that the third wave will be less devastating than the
second wave. The conclusion is based on the plausible assumption that many who have
been infected earlier would retain their immunity, fully or partially. The situation could
change if new variants arrive which override the immunity provided by earlier infections.
Even then, it is unlikely that new variants will be more virulent. While they may infect
more people, it is unlikely that they will cause more severe disease. That holds true for
protection from vaccine too. New variants may display higher levels of vaccine evasion,
but most vaccines will still provide a fair amount of protection against severe disease and
death. Our health and management system will also be better prepared than they were
during the second wave, which is when they were caught off guard. For all of the above
scientific reasons, the possibility of third wave is very less likely to be severe than the sec-
ond. If the wave occurs, it would not cross the positivity rate >10% and there will be less
numerator value of hospitality, our demonstrated model suggested. However, many health
experts eagerly pointed out that the infection will still tend to be milder in children. The
ACE-2 receptors on human cells, which the virus attaches to for entering the body’s organs
and blood vessels, are not as extensively developed in children as in adults. Children also
have lesser prevalence of associated health conditions such as hypertension, diabetes,
heart disease, and lung disorders that increase the risk of SARS-Cov-19 disease. A small
proportion will suffer from multi-system inflammatory disease of children (MIS-C), but
the vast majority of children will have mild course. Increasing healthcare facilities for
children, including intensive care units, will still be useful as they will serve the needs of
many other health conditions. One more study reported in India, study suggests that
increasing vaccination drive is of high priority. The SARS-Cov-19 vaccines will confer
stronger and longer immunity than natural infection that has a variable RNA plasma viral
load. If we achieve 60% coverage, the rates of infection and deaths will steadily come down
as we have seen in Serrana Province of Brazil. Even if we lift lockdown after the second
wave recedes, we must ensure disciplined observance of public health advisories on mask-
ing, ventilation, avoidance of crowding, and non-essential travels. Super spreading events
must be forbidden for rest of the year. An inception of home isolation for infected persons
and travelers, provide emergency transport, secondary health care facilities with oxygen
and well-equipped tertiary care hospitals with intensive care units meticulously planned,
prepares and monitored for response preparedness and efficient functioning. People
should be sensitized to the disease interventions and must be strengthened through moral
supports. Indian Institute of Technology Kanpur and Government of India research team
(Ranjan et al., 2021; Shanmugam and Singh, 2021; Rodríguez et al., 2020; Wu et al., 2020b)
developed an SIR mathematical model for the estimation of the theoretical number of peo-
ple infected with contagious illness in closed population over time. Three scenarios of
possible third wave (restrictions are lifted, infectious variants of SARS-Cov-2, and no lock-
downs or restrictions) using the data from the second wave in India were constructed for
the prediction of third wave surge. The study derived that the peak of the third wave
would be delayed until late October 2021; with strict social distancing, the peak would be
lower than the surge of the second wave. The demonstrated model takes into account the
vaccination drive and including more recent data sets on the same is being worked out
(Xu et al., 2020; Yang et al., 2020). The demonstrated SIR model had certain limitations. It
was assumed that the entire population is equally susceptible to the virus, it does not take
into account the effect of vaccination, and it assumed that the population is closed. There
is no migratory flow in or out, so the changes in the population occur through births and
mortality only. Further, vaccination is known to break the transmission chain and the for-
mulated model does not include vaccination parameters. But the model we demonstrate
has included vaccination drive and clinical and epidemiological parameters. We estimated
each parameter and the real probability, and the Bayesian classifier was superimposed to
the frequentist analysis (because Bayesian model had limitations). Finally, the formulated
model was cross-checked by the diagnosis test of sensitivity analysis. Considering sensi-
tivity, our model significantly yielded better results than any other models formulated by
scientists, and also the model output is very excellent for predicting the surge of different
waves of SARS-Cov-19 considering massive data sets. The studies reported by Miller et al.
(2020) and Zheng et al. (2019) developed Sutra model. The predicted model has three sce-
narios such as optimistic, intermediate, and pessimistic. The most optimistic scenario pre-
dicted that the quality of life would return to normal by August 2021 and that a fewer
number of new mutant virus would be exhibited over a period of time. The intermediate
scenario, in addition to the above parameters, predicted the vaccination would be 20 per-
cent less effective than the most optimistic scenario. In the case of the pessimistic scenario,
it differs from the intermediate one: Over the past 2 years, the severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2) caused the coronavirus disease 2019 (COVID-19)
and rapidly spread worldwide. In the process of evolution, new mutations of SARS-CoV-2
began to appear to be more adaptable to the diverse changes of various cellular environ-
ments and hosts. Generally, the emerging SARS-CoV-2 variants are characterized by high
infectivity, augmented virulence, and fast transmissibility, posing a serious threat to the
prevention and control of the global epidemic. According to the above model, the second
wave switch over by mid-August 2021 and the third wave could reach its peak between
October and November 2021. However, again the model demonstrated by the authors had
more limitations. The model was fitted based on the assumed factors and does not con-
sider epidemiological, clinical, and biological parameters. Also, the robustness of the
model was not tested by relevant tools.
7.6 Conclusions
In realistic analytical approach, predictive models are very useful for the estimation of
surge of SARS-Cov-19. However, various structured and unstructured models were devel-
oped by many mathematicians worldwide. All these formulated models were combined
with mathematical simulations and data validations as well as employed some statistical
techniques for the estimation of likelihoods of pandemic crisis. There is no doubt that their
findings have covered a wide range of variability of epidemiological, clinical, and virologi-
cal characteristics associated with SARS-Cov-19, and we improved our understanding of
the complex transmission mechanism. However, there are several limitations in the cur-
rent model because scientists made certain assumptions before the construction of model
settings. Besides analytical gap, biologically, some of the relevant traits or parameters
were excluded from the theoretical and practical postulates. Most of these driven pro-
jected models were demonstrated based on the SEIR framework and exclusively focused
on the direct, human-to-human transmission pathway. They do not consider knowing
the mechanism of virus and host factors. In practice, the transmission rates and forecast-
ing of various COVID waves may change with epidemiological, socioeconomic, clinical,
behavioral, and host parameters. The present study resolves these problems. We consid-
ered all parameters and obtained real probability from Bayesian classifier, and the model
was superimposed to frequentist approach. Then we estimated the probable chance of
COVID third wave in Indian setup. As per the model output, the third wave will be less
devastating in India and the percent positivity rate will not reach >10%. The present model
output will help to plan the policy and to implement prevention strategies to eradicate
SARS-Cov-19 worldwide and will also leverage the support of other analytical techniques
and computational biology.
References
Adolph C., Amano K., Bang-Jensen B., Fullman N., Wilkerson J. Pandemic politics: Timing state-level
social distancing responses to Covid-19. J Health Polit Policy Law 2020; 46: 8802162.
Ainslie K.E., et al. Evidence of initial success for China exiting Covid-19Social distancing policy after
achieving containment. Wellcome Open Res 2020; 5: 81.
Anderson K.G., Rambaut A., Lipkin W.I., Holmes E.C., Garry R.F. The proximal origin of SARS-
CoV-2. Nat Med 2020a; 26: 450–452.
Anderson R.M., Heesterbeek H., Klinkenberg D., Hollingsworth T.D. How will country-based
mitigation measures influence the course of the Covid-19 epidemic. Lancet 2020b; 395:
931–934.
Backer J.A., Klinkenberg D., et al. Incubation period of 2019 novel Corona virus (2019-nCoV) infec-
tions among travellers from Wuhan, China, 20–28 January 2020. Euro Surveill 2020; 25(5):
2000062. doi: 10.2807/1560-7917.
Bar-Zeev N., Moss W.J. Encouraging results from phase 1/2 Covid-19 Vaccine trials. Lancet 2020; 396:
448–449.
Barzilai O., Ram M., Shoenfeld Y. Viral infection can induce the production of autoantibodies. Curr
Opin Rheumatol 2007; 19: 636–643.
Bjørnstad O.N., Shea K., Krzywinski M., Altman N. Modeling infectious epidemics. Nat Methods
2020a; 17: 455–456.
Bjørnstad O.N., Shea K., Krzywinski M., Altman N. The SEIRS model for infectious disease dynam-
ics. Nat Methods 2020b; 17, 557–558.
Boulware D.R., et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for
Covid-19. N Engl J Med 2020; 383: 517–525.
Cairoli E., Espinosa G. Autoimmune diseases and vaccines against Covid-19. Decision making in
Uncertain Scenarios. Med Clin (Barc) 2021; 28(5): 296–297.
Chu D.K., et al. Physical distancing, face masks and eye protection to prevent person-to-person trans-
mission of SARS-CoV-2 and Covid-19: A systematic review and meta-analysis. Lancet 2020; 395:
1973–1987.
Cobey S. Modeling infectious disease dynamics. J Sci 2020; 368(6492): 713–714.
Cohen A., Shoenfeld Y. The viral autoimmunity relationship. Viral Immunol 1995; 8: 1–9.
Ehrenfeld M., Tincani A., et al. Covid-19 and autoimmunity. Autoimmun Rev 2020; 19(8): 102597. doi:
10.1016/j.autrev.2020.102597.
Fine P., Eames K., Heymann DL. Herd immunity: A rough guide. Clin. Infect Dis. 2011;52: 911–916.
Flaxman S., et al. Estimating the effects of Non-Pharmaceutical interventions on Covid-19 in Europe.
Nature 2020; 584: 257–261.
Jamilloux Y., Henry T., Belot A. Should we stimulate or suppress immune responses in Covid-
19? Cytokine and anti-cytokine interventions. Autoimmune Rev 2020 doi: 10.1016/j.
autrev.2020.102567.
Kucharski A.J., Russell T.W., Diamond C., et al. Centre for mathematical modelling of infectious
diseases Covid-19 working group. Early dynamics of transmission and control of Covid-
19: A mathematical modelling study. Lancet Infect Dis 2020; 20(5): 553–558. doi: 10.1016/
S1473-3099(20)30144-4.
Lauer S.A., et al. The incubation period of Covid-19 from publicly reported confirmed cases:
Estimation and application. Ann Intern Med 2020; 172: 577–582.
Leung K., Wu J.T., Liu D., et al. First-wave Covid-19 transmissibility and severity in China outside
Hubei after control measures, and second-wave scenario planning: A modeling impact assess-
ment. Lancet 2020a; 395: 1382–1393.
Leung N.H.L., et al. Respiratory virus shedding in exhaled breath and efficacy of face masks. Nat
Med 2020b; 26: 676–680.
Liang M., et al. Efficacy of face mask in preventing respiratory virus transmission: A systematic
review and meta-analysis. Travel Med Infect Dis 2020; 36: 101751.
McBryde E. The value of early transmission dynamic studies in emerging infectious diseases. Lancet
Infect Dis 2020; 20(5): 512–513.
Miller I.F., Becker A.D., Grenfell B.T., Metcalf C.J.E. Disease and healthcare burden of Covid-19 in the
United States. Nat. Med 2020; 26, 1212–1217.
Ngonghala C.N. et al. Mathematical assessment of the impact of non-pharmaceutical interventions
on curtailing the 2019 novel coronavirus. Math Biosci 2020; 325: 108364.
Nishiura H., Jung S.M., Linton N.M., Kinoshita R., Yang Y., Hayashi K., et al. The extent of transmis-
sion of novel Corona virus in Wuhan, China, 2020. J Clin Med 2020; 9(2): 330.
Ranjan R., et al., 2021. IIT team forecasts three scenarios of possible 3rdCovid wave, using data from
2nd. Prediction model assumes India will fully unlock by 15 July, doesn’t take vaccination into
consideration. https://theprint.in/health/3-likely-scenarios-for-3rd-wave-peak-in-sept-oct-
2-5-lakh-cases-day-iit-k-team-predict/682257/.
Read J.M., Bridgen J.R.E., Cummings D.A.T., et al. Novel Corona virus 2019-nCoV: Early estima-
tion of epidemiological parameters and epidemic predictions. medRxiv 2020. doi: 10.1098/
rstb.2020.0265.
Rodríguez Y., Novelli L., Rojas M., et al. Auto inflammatory and autoimmune conditions at the cross-
road of Covid-19. J Autoimmune 2020; 11(4): 102506. doi: 10.1016/j.jaut.2020.102506.
Shanmugam R., Singh K.P. Structural zero data of Covid-19 discovers exodus probabilities.
J Multidiscip Healthc 2021; 15(14): 1443–1449.
World Health Organization. Novel coronavirus disease (2019-nCoV) Situation Report 1, 2020.
Wu J.T., Leung K., Leung G.M. Nowcasting and forecasting the potential domestic and international
spread of the 2019-nCoV outbreak originating in Wuhan, China: A modeling Study. Lancet
2020a; 395: 689–697.
spread of the 2019-nCoV outbreak originating in Wuhan, China: A Modelling study. Lancet
2020b; 43(5): 1951–1956.
Xu B., et al. Open access epidemiological data from the Covid-19 outbreak. Lancet Infect Dis 2020; 20:
534.
Yadav P. D., et al. Isolation and characterization of the new SARS-CoV-2 variant in travellers from
the United Kingdom to India: VUI-202012/01 of the B.1.1.7 lineage. J Travel Med 2021: 1–3. doi:
10.1093/jtm/taab009.
Yang Z., Zeng Z., Wang K., et al. Modified SEIR and AIP prediction of the epidemics trend of
Covid-19 in China under public health interventions. J Thorac Dis 2020; 12: 165–174.
Zheng P., Aravkin A.Y., Barber R., Sorensen R.J., Murray C.J. 2019. Trimmed constrained mixed
effects models: Formulation and algorithms. Preprint at https://arxiv.org/abs/1909.10700.
8
Risk Analysis of COVID-19—
Vetted by Real Data Sets
8.1 Introduction
Risk is a pervasive condition of human existence, in other words a condition in which there
is a probability of an adverse deviation from the desired outcome, i.e., expected or hoped
for. Thus, risk is a combination of circumstantial challenges and in the combinations of
different problems lead to possibility of loss of quality of life (Tamara and Tahapary, 2020;
Wang et al., 2021; Yang et al., 2020). Mathematically, risk may be defined as the product of
the probability of the event and impact factor. Risk analysis is widely used in the context
of health, safety, and environment. It involves evaluation of existing conditions of vulner-
ability, the impending hazard, existing exposure, and current capacities for prevention.
The risk analysis will specify the salient health attributes that are needed to assess the risk
and the correlation among those attributes, producing a sort of template for risk assessors
to use in their assessments. SARS-Cov-19 health risk assessment tools have been devel-
oped to evaluate the risk to the population exposed and unexposed to nCov19. COVID-19
pandemic is a public health emergency and has brought to light many challenges in our
lives and livelihoods. It has brought in the picture the need for a transdisciplinary view
of the current crisis from various angles of global governance, technology, risk commu-
nication, etc. SARS-Cov-19 has posed not only health, but also economic, geographical,
demographical, and political crisis. It is thereby a humanitarian challenge, while WHO
and government authorities have advised many prevention strategies and measures have
been taken for the control of pandemic, viz. partial lockdown, complete lockdown, com-
pulsory wearing of masks, social distancing, and personal hygiene. One of the foremost
strategies remains risk communication and awareness generation to break the chain of
spread. Awareness and understanding of the risk at the population level goes a long way
in enhancing prevention. In this context, various assessment tools are available in virtual
mode. Such tools are intended to compile the probable risk to the respondents based on
information provided on current pandemic crisis. Iavicoli et al. (2021) studied risk assess-
ment at work and prevention strategies on COVID-19 in Italy. Their research finding was
that reopening is needed that involves a stepwise approach, including risk-based criteria
to identify eligible sectors and allowing adequate intervals between phases to assess the
impact of each one on the control of the pandemic (Mendoza- Jiménez et al., 2021). The
proposed approach will contribute to rethinking how work is organized; also to include
innovation, with integration in the OSH national system, the model will contribute to the
prevention and early identification of the outbreaks in the workplace in the future stages
of the pandemic. The risk assessment tools of WHO (2021) provide a user-friendly way
DOI: 10.1201/9781003204794-8 237

FIGURE 8.1
Flowchart of basic risk model in health science.
for health authorities and organizers to understand the level of risk. An upcoming mass
gathering may increase the further spreading of COVID-19, both within a country and
globally, scientists, epidemiologists and planner of the policies had learn about the precau-
tionary measures and preparedness of next pandemic that can be applied to the planned
event to mitigate the problems at early stage of infection or risks. It is very important to
analyze the following risks, viz. generic risk, sports and mass gathering risks, the risk of
religious mass gathering, and finally the economic risk. The risk analysis provides author-
itative guidance on the fundamental principles to be adopted when conducting risk analy-
sis to obtain high-quality health policy decisions and trustworthy treatment. Risk analysis
approaches and methods for assessment are very important to obtain a high degree of rela-
tion between human values and ethics and also simultaneously condense societal errors
of pandemic crisis. The flowchart of the process of risk analysis is presented in Figure 8.1.
The fundamental basic principles are necessary to ensure the risk analysis applications
and methodology aspects. However, risk analysis is not broadly recognized as a sepa-
rate/distinct science. The first stage of risk analysis is monitoring, reviewing, recording,
and reporting, followed by communications and consultations embedded with vicious
circle of overall risk assessment, which includes risk evaluation, risk mitigation, and risk
communication to the COVID-affected and COVID-unaffected population. Risk is always
a challenge to balance the need for authoritative guidance and overall solutions on the
one hand, and the need for continuous debate, research, and improvement on the other
(Patanavanich and Glantz, 2020; Reddy et al., 2021). In any pandemic crisis, research on
risk analysis is a pragmatic approach to building confidence of health policymakers as
well as frontline healthcare workers and general public. It provides analytical arguments
Risk Analysis of COVID-19 239
on how to conduct risk analysis and make decisions for disease eradication, and also these
research findings can reflects the planner of the policy to incept insights solutions into
these issues obtained from both theoretical and practical postulates for affected popula-
tion and save millions of people during the crisis (Shiina et al., 2021; Raudenbush and
Bryk, 2002; Rosenstock, 1974). Risk analysis is the platform to construct rapport between
epidemiological researchers, policy makers, mathematicians, clinicians, regulators, jour-
nalists, and research scholars to ensure prudent risk analysis and high-level debate at an
international platform. This chapter constructs various risk models to know the perennial
changes caused by SARS-Cov-19 pandemic crisis in the health sector.
We consider X1, X2…Xn as the random variables of COVID-19 risk indicators. They are
normally distributed with mean and common variance, and all observations are identical
and independent in nature (i.i.d.). In case of COVID 19 qualitative attributes or variables
for demonstration of formulated model , we considered the variables of interest and all
data sets were transformed by suitable data transformation scale (logarithmic or angular
sine inverse transformation) (Data transformation techniques). The transformed scale was
modeled by a suitable mathematical equation.
1
Yt =
e a + b0X 0 + b1X1…bnX n (
, Xn ~ N µ , σ 2 ) (8.1)
1
Yt = a + b0X 0 + b1X1…bnX n
, X n ~ Binomialn ( p , q ) (8.2)
e
p = probability success of COVID risk

q = (1−probability success of COVID risk)
At population level, we estimated risk by the following model:
Risk = Probability*Impact
 p×q 
Impact =   *100 (8.3)
 SE ( coeffcients ) 
 0.68 × 0.32 
Impact =   *100
 1.25 ( X 1 variable ) 
Impact = 17.40
Risk = 0.68 * 17.40
Risk ( % ) of X 1variable = 0.68 * 17.40 = 11.82%; the low, medium, and high augmentations
were calculated based on the risk percentage. If the percentage expression is ≤30%, it is
considered as low risk; if it is 30%–50%, it is medium risk; and if it is 51%–>60%, it is high

risk. Furthermore, factor analysis (FA) was carried out for the simulation of intercorrelated
variables (it is the family of multivariate statistical techniques for examining correlation
amongst variables). The main application of “FA” is to develop direct and indirect test
structure data in the relationship between variables and also to identify the latent effect of
factors classification. Another very important practical approach of FA is that the test sta-
tistics of FA will be reduced number of massive data or parameters of interest. Presently,
confirmatory factor analysis was employed to test the correlative structure of a data set
against a hypothetical basis and explore the goodness of fit.
Model is formulated by considering with four factors and 16 variables which tap or rep-
resents four underlying factors of COVID risk. Each measurement was loaded on different
sub-sachets of risk indicators. The factors modeled are as follows:
X i ( i = 1, 2 … p )
X i = µi + ai 1 FA + ai 2 FB + ai 3 Fc + ai 4 FD ….aim Fm + ε (m ≤ p) (8.4)
 X1   µ1   a11 a12 a13 a1m 

     
 X2  =  µ2  +  a21m a22 m a23 m aa 2 m  (8.5)
 Xn   µn   ap1 ap 2 ap 3 apm 
     
( X − µ ) = AF + ε (8.6)
E ( F ) = 0; E ( ε ) = 0 Cov ( F ) = I m
(
E(ε ) = Cov(ε ) = diag σ 12 , σ 22 …σ m2 )
Cov ( F , ε ) = 0
( X − µ ) = AF + ε
Cov ( X − µ )′ = A Cov ( F ) AT + Cov ( ε ) (8.7)
(
Cov ( X ) = AAT + diag σ 12 , σ 22 σ m2 ) (8.8)
h2 i = ∑a
i=1
ij
2
; the variance of X i is the communalities. It is the sum of squares of the elements
of the ith row of the factors.
Var ( X i ) = ai21 Var ( F1 ) + ai21 Var ( Fm ) + Var ( ε i ) (8.9)

n
1= ∑a
i=1
2
ij + σ 12 (8.10)
TABLE 8.1
Objective Risk Stratification (ORS) Tools for Individuals
Risk Factor Indicators No Odds Adjustment
Age (years) <20 ≤1%–5% <1 1
30–40 18% 3.55 2
41–50 22% 4.22 3
51–60 25% 5.03 4
>61 30% 8.97 5
Gender Male 65% 3.65 1
Female 30% 2.28 2
Others 05% <1 3
Diabetes and obesity (Type 1 or Type 2) uncomplicated 18% 4.63 1
(Type 1 or Type 2) complicated 45% 6.33 2
BMI≥35 kg/m2 37% 5.27 1
Cardiovascular disease Angina, previous MI, stroke, or cardiac 56% 10.25 1
interventions 14% 2.18 2
Heart failure
Pulmonary disease Asthma 67% 12.87 1
Non-asthma chronic pulmonary disease 33% 9.88 1
Either of the above requiring oral 22% 8.42 1
corticosteroids in the previous year
Malignant neoplasm Active malignancy 19% 3.01 3
Malignancy in remission 5% <1 1
Rheumatologic conditions Active treated conditions 11% 2.22 2
Immunosuppressant therapy Any indication 8% <1 2
Chronic kidney disease CKD3 or CKD4 7% <1 2
End-stage renal disease/transplant 13% 6.08 2
Chronic liver disease 2% <1 2
Any active disease 4
Immunosuppressant therapy Any indication <5% <1 1
Risk Score
Low risk <3
Moderate risk 3–5
High risk ≥6
The equimax and varimax rotations were done to know the significant risk factors for
SARS-Cov-19. The following risk stratification tools were used for assessment (Table 8.1).
8.3 Numerical Model Output

This chapter explores and demonstrates SARS-Cov-19 third wave based on advanced
modeling techniques. The study addresses the plausibility of third wave hit in India. This
technique derives a qualitative and quantitative approach for the estimation of surge of
the third wave and risk factors for pandemic diseases, while also illustrating the likeli-
hoods of prediction factors. As per the model output, we noted that the projections were
subjected to behavioral vaccination, policy implication, and preparedness to mitigate the
scale-up of vaccination drive at population level. Table 8.2 depicts that the risk analysis for
242
TABLE 8.2
Risk Analysis for the Prediction of the Surge of the Third Wave of COVID-19 (Less Impact)
Predictor Coefficient SE Coefficient t Value P Value Interpretation Augmentation
Sanitizer usage −2.95 0.42 <1 0.70 Insignificant <1% Low
Vaccinated −0.09 0.02 <1 0.91 Insignificant <1% Low
Risk of third wave in children −1.21 0.012 <1 0.15 Insignificant 5%–10% Low
Adult 1.25 0.01 0.91 03387 Significant 25%–40% Medium
Lack of mask 3.55 0.008 0.06 2.08 Significant 30%–95% High to high
Lack of family member hygiene 5.74 0.004 0.43 3.676 Significant 29%–67.6% Moderate
Irrespective of age 5.6 0.332 1.76 2.860 Significant 40%–86% High to high
Organizing a ritual conference/ 3.33 0.262 2.58 3.760 Significant 37%–76% High to high
festival/marriage
Lack of social distance 7.45 0.002 0.28 5.788 Significant 25%–78.88% Moderate to high
Travel history 8.88 0.007 0.26 6.803 Significant 57%–80.30% High to high
OIs 2.22 0.003 0.68 3.131 Significant 7%–13% Low to medium
Comorbidity >1 at least 3 3.33 0.001 4.88 5.887 Significant 50%–88.70% High to high
Ignorance of COVID policy 4.58 0.137 0.58 4.733 Significant 41%–73.33% High to high
Unvaccinated 6.51 0.08 0.27 3.841 Significant 62%–84.1% High to high
S = 0.176348; R-Sq. = 94.3%; R-Sq. (adj.) = 85.0%.
the prediction of the surge of third wave of COVID-19 shows low prevalence. An estima-
tion was found to be suboptimal movement between various risk factors for SARS-Cov-19,
strict implementation of policy, regular usage of sanitizer, maintaining social distancing,
and compulsory wearing of masks, and vaccination of exposed and unexposed popu-
lation will reduce the event of surge of the third wave. The study found that sanitizer
usage [coefficient −2.95, SE 0.42; t value 2.09; p < 0.01], vaccinated population [coefficient
−0.09, SE 0.00; t value 3.46; p < 0.01], and risk of third wave in children [coefficient −1.21,
SE 0.02; t value 2.59; p < 0.01] are insignificantly correlated with the third wave and aug-
mentation was very low (<1% augmentation). A similar analysis shows that lack of mask
[25%–40%, medium augmentation], lack of family member hygiene [30%–95%, high to
high], irrespective of age [40%–86%, high to high], organizing a ritual conference/festival/
marriage [37%–76%, high to high], lack of social distance [25%–78.88%, moderate to high],
opportunistic infection [7%–13%, low-to-medium augmentation], comorbidity >1 (estimate
severity of the disease) at least 3 [50%–88.70%, high to high], ignorance of COVID policy
[41%–73.33%, high to high], and unvaccinated [62%–84.1%, high to high] were found to be
correlated with the surge of the third wave. However, in the above model construction, the
mechanism of possibility of waning immunity was considered for the weightage factors
that would be put in to previously exposed individual at risk. Second, the emergence of a
new viral variant that is capable of escaping immunity to previously spread the surge of
wave strains and common variants. Third, policy implications were suggested for the con-
trol of surge (lockdown, wearing of a mask, and other preventive measures were consid-
ered). Various risk factors were correlated during the study intervention. Health risk was
more prevalent (40%, p = 0.001; odds 6.33), followed by economic (25%, p = 0.001; odds 4.22),
behavior (20%, p = 0.0157; odds 3.08), exposure (10%, p = 0.087; odds 2.58), and policy risk
factors (5%; p = 0.0947; odds 1.89) (Figures 8.2 and 8.3). All risk domains were significantly
correlated with the pandemic crisis. Rank or weightage of individual facets of health indi-
cator, behavioral, economic, and policy domains was diagnosed normally, and all domains
were found to be in normalcy with a mean of 55.45 and SD of 8.56. Parameter response
was positive to increase the changes of COVID pandemic and risk-associated parameters.
Scores were assigned on a 0–5 scale: health risk 5, economic 4, behavior 3, exposure 2, and
social policy 1 (Table 8.3) (Figure 8.4).
As per the study findings, adults of any age group with the following underlying clinical
conditions can be more likely to get severe illness from SARS-Cov-19. Severe illness means
that a person with nCov may need hospitalization, intensive care, a ventilator to help them
breath (Spo2 80%–84%), or they may even die. Age factor is one of the indicators: People
in the age group of 60–70 years with one or more underlying comorbid conditions get
severely ill from SARS-Cov-19. More than 80%–90% of COVID-19 deaths occur in people
older than 60 years and above median 66 years (IQR 60–73 years), and more than 95% of
FA FB FC FD
a1 a 2 a 3 a 4
FA: Health risk (HR) FB: Covid Exposure (Ex) FC: Social Policy (SP) and FD: Economic risk (Er)
FIGURE 8.2
Risk of COVID-19 on perspective basis.
FIGURE 8.3
COVID-19 Risk factors variation at the population level.
TABLE 8.3
Distribution of Risk Type and Data Frequency Weightage
Risk Type Weightage Score
Health risk (HR) 40% 5
Behavior (Be) 20% 3
Exposure (Ex) 10% 2
Social policy (SP) 5% 1
Economic risk (Er) 25% 4
Normal Probability Plot

(response is Positivity)
99
95
90
80
70
60
Percent
50
40
30
20
10
1
-3 -2 -1 0 1 2 3
Standardized Residual
FIGURE 8.4
Normal probability plot response positivity rate.
deaths occur in people older than 45 due to drug side effects, anxiety, and fear of COVID.
Furthermore, chronic lung diseases, including COPD, asthma (moderate to severe), inter-
stitial lung disease, cystic fibrosis, and pulmonary hypertension, may increase the case
fatality rate in the elderly population, which is significantly associated with opportunistic
infections such as black fungus (mucormycosis) and white fungus [p = 0.0018; odds 10.85;
CI 95% 0.55–0.98]. People with dementia [P < 0.01, odds 3.44; CI 95%:0.74-0.83], down syn-
drome, coronary artery disease (cardiomyopathies or hypertension) [P < 0.01, odds 2.86, CI
95% 0.68–0.82], HIV infection [P < 0.01, odds 4.16, CI 95% 0.33–0.79 ], immunocompromised
state, chronic liver disease [P < 0.01, odds 2.86, CI 95% 0.25–0.67], and/or overweight and
obesity [P < 0.01, odds 5.68, CI 95% 0.57–0.82 ] (overweight: BMI > 25 kg/m2, but <30 kg/m2;
obesity: BMI >=30 kg/m2, but <40 kg/m2; severe obesity: BMI >=40 kg/m2) are more likely
to get severely ill from SARS-Cov-19. The risk of COVID illness increases sharply with
elevated BMI. Furthermore, health risk factors were correlated based on the primary data
sets: pregnancy [P < 0.01, odds 1.81, CI 95% 0.25–0.47], sickle cell disease or thalassemia
[P < 0.01, odds 2.55, CI 95% 0.32–0.55], smoking (current or former) [P < 0.01, odds 6.12, CI
95% 0.63–0.88], stroke or cerebrovascular disease [P < 0.01, odds 8.56, CI 95% 0.78–0.99],
substance use disorders [P < 0.01, odds 2.77, CI 95% 0.12–0.38], etc., increase the mortality
rate of COVID-19 and sharpen the post-therapy complications after infection. While chil-
dren have been less affected by SARS-Cov-19 compared to elderly adults, children can be
infected with virus that causes infections and develops severe illness. After therapy, some
of the children were severely affected by COVID-associated multi-system inflammatory
syndrome (MIS-C). Children with MIS-C have fever (IQR 105–110°C), and inflammation
in their body is confirmed by laboratory tests. However, different MIS-C have different
symptoms such as Kawasaki disease and toxic syndrome, which were significantly cor-
related in younger children who infected by COVID-19. The case with MIS-C may also
have thrombosis (blood clots), poor heart function, and kidney injury, which are the com-
monest symptoms found in children. The present study also correlated that children with
medical complexity along with neurological and metabolic conditions or with CHD can be
at an increased risk (P = 0.78) of severe illness from SARS-Cov-19. Precautionary measures
would be needed for children who are affected by MIS-C, for example a follow-up of 2 or 3
weeks after discharge from the healthcare center. Because MIS-C can cause the wall of the
heart to be inflamed (myocarditis), patients with myocarditis will be restricted from activi-
ties such as physical exercise even for a short period of time. Children treated with ste-
roids or a biological medicine should also be followed up with a pediatric rheumatologist.
Further, behavioral risk factors such as smoking, excessive alcohol consumption, physical
inactivity, obesity, and intake of unhealthy food are added risk factors for severe outcomes
of SARS-Cov-19 infections and complications. Preventive measures to avoid infections are
therefore particularly important for an individual engaging in activities associated with
behavioral risk factors. Table 8.4 shows the model output of various risk factors: health
communality (52.5%); behavior (66.62%); exposure (69.40%); social policy (45.30%); and eco-
nomic (30.20%) with a pooled variance of 2.63, and the overall percent variance was 0.527.
Varimax rotation was done, and the rotated factor loadings and communalities are shown
in Table 8.5. The significant communalities of COVID risk factors were health (52.5%) and
behavior (66.20%).
Multilevel factor analysis was done to know the significant factors to reduce the risk of
COVID. The BRF was significantly associated with less adherence to hygiene and preven-
tive measures such as hand sanitizing, hand washing, wearing masks, covering coughs
and sneezes, avoiding crowded place, maintaining social distance, which are significantly
attributed factors to reducing the risk or burden of COVID-19 (mean eigenvalue was >2;
TABLE 8.4
Factor Analysis of Unrotated Factor Loadings and Communalities
Variable F1 F2 Communality
Health 0.105 0.717 0.525
Behavior −0.695 0.422 0.662
Exposure 0.829 0.085 0.694
Social policy 0.193 0.644 0.453
Economic −0.548 −0.044 0.302
Variance 1.51 1.11 2.63
%Variance 0.304 0.223 0.527
TABLE 8.5
Rotated Factor Loadings and Communalities
Varimax Rotation
Variable Factor1 Factor 2 Communality
Health 0.002 −0.725 0.525
Behavior 0.750 −0.315 0.662
Economic
Second Factor
0 Exposure
Behaviour
Social policy
Health
-1
-2
-2 -1 0 1 2
First Factor
FIGURE 8.5
Scattered distribution and correlation of factors in varimax rotation.
Figure 8.5). The present analytical study provides important insights into addressing the
various preventive behaviors of some of the most vulnerable population. Due to their risk
alone, the infected population are at high risk of morbidity and mortality of underlying
comorbid conditions. As additional risk factors, we explored the behavioral risk factors
such as smoking, chronic alcohol consumption, intake of unhealthy foods, physical inac-
tivity, and obesity, and it was shown that these were associated with high risk of SARS-
Cov-19. In this context, significant differences were seen regarding lack of family support,
far away health service center, lack of finance to access health services during infection,
and social mobility measures, which increased the progression of disease condition, and
they would be deeply penetrated at grassroots level. Multilevel factor analysis was done
with age and sex. The results show that health and economic indexes are the most vulner-
able factors attributed to the illness of a person. The index score was very high, i.e., >100%,
and augmented with mortality and morbidity (Figures 8.6 and 8.7).
Regarding our research hypothesis, the resultant findings showed a significant asso-
ciation between behavioral risk factors and prevention related to social distancing, good
hygiene, regular sanitization of hands, covering of coughs and sneezes, more often to
120 Variable
Health
Behaviour
Exposure
100 Social policy
Economic
80
Data
60
40
20
0
3 6 9 12 15 18 21 24 27 30
Index
FIGURE 8.6
Index variation of various risk factors.
18
15
Exposure
12
25
9
20
Behaviour
15
40
48
Health 56
FIGURE 8.7
Magnitudinal differences of risk factors in relation to exposure.
visited public places than before contacted, adhering to government health policy, compul-
sory wearing of masks, and less exposure to public places or crowded areas. Our empiri-
cal study found that people with preexisting clinical conditions are more likely to follow
the preventive measures, particularly those involved in public meeting, ritual conference,
shopping, and meeting with others frequently. In this regard, there is an increased risk of
spread of disease at the rate of probability p = 0.84 (odds 11.54). The augmented model also
demonstrated that we correlated other factors such as intoxicated or unprotected sexual
intercourse with asymptomatic patients, less hours of sleep, and the use of substances such
as nicotine gum and other products and show that they may drastically increase the infec-
tion rate progressive factors that increase the risk of COVID.
8.4 Discussion
This study attempted to explore the various analytical interventions of nCov19 risk deter-
minants. The disease severity has approached various risk indicators, ranging from
low-to-medium, medium-to-high, and high-to-high augmentations. A new model was
developed for accurate simulating and exploring the risk factors for the surge of differ-
ent waves of COVID. The severity of disease will vary in different regions. There exists a
highly significant correlation between COVID-affected population which is derived from
asymptomatic infection to severe respiratory distress and failure event. We evaluated the
potential of an early stratification at population level considering health, economic, expo-
sure, and policy risk factors (Meader et al., 2016; Muto et al., 2020; Noble et al., 2015). This
study found that health and economic indicators were significantly correlated with the
surge of different waves of SARS-Cov-19. Indian economy is in a state of paralysis as the
novel coronavirus impact has forced countries to take extreme measures for safety of their
citizens. As per the model output, economy is the second highest risk factor for the spread
of the disease at population level. Because of lack of literacy, public healthcare centers, and
access to resources, infected patients were not able to get timely access to the healthcare
services. The pandemic has exploited the weakness at grassroots level, especially in rural
side. The situation worsened in the second wave of SARS-Cov-19 that hit in the months
from April to June 2021. Health risk was more prevalent, followed by economic, behavior,
exposure, and policy (Lustria et al., 2013; Mendoza-Jiménez et al., 2021; Meader et al., 2016).
All risk domains were significantly correlated with the pandemic crisis. However, in case
of policy implications in India, preventive strategies such as lockdown show a multicol-
linearity effect between Indian economy, health, and behavioral factors. In the meantime,
the Government of India has taken many initiatives and measures to defend the country
against deadly virus. However, to devise an effective strategy for fighting COVID and
maximizing the results, it is crucial identify the internal and external factors correctly. The
present research findings assessed the current scenario in tackling the pandemic and the
formulation of new guidelines in case of surge of COVID waves. In connection with health
risk, we had many challenges and critics in fighting COVID because of the lack of test-
ing kits and relief materials such as medical equipment, PPE, masks, and life-supporting
equipment such as ventilators. Challenges in manufacturing testing kits and relief mate-
rials and medical equipment indigenously make us dependent on imports. In addition,
lack of awareness in specific groups of the society, psychological barriers relating to isola-
tion—people deliberately rejected isolation and escaped from the policy, lack of ability
to identify the population that are highly susceptible to diseases, poor immunity, high
incubation period of virus, difficulty tracking asymptomatic patients and hidden carriers
in high prevalence states are some of the other challenges faced. Another risk factor is the
shortage of emergency healthcare infrastructure and professionals: Data obtained from
NIHFW, GOI, show a doctor-to-patients ratio of 1:1445, hospital beds-to-people ratio of
0.7:1000, and ventilators-to-population ratio of 40000:1.3 bn. Furthermore, failure in con-
tact tracing may lead to worsening of the surge of second wave, potentially increasing
the case fatality rate and infectivity and also increasing the probability of being hit by
the second wave of COVID-19. However, this study also found that the majority of the
population perceived the SARS-Cov-19 pandemic as being serious or very serious, and
the eigenvalue of factor analysis is >2–2.5 and all risk factor domains were strongly associ-
ated with various risk factors to mitigate the output of the study. These results are more
congruent with those of other studies done by Barceló et al. (2020), Heydari et al. (2021),
Hamer et al. (2020). They reported that adults in the age group 40–45 years had a moder-
ate to high level of risk of COVID-19. However, the results show similar findings to those
reported in individuals. High-to-high augmentation was seen in health risk, exposure, and
behavioral components, which perceived susceptibility at early stage and highly perceived
severity during the time of admission and, at the same time, transmissibility (Figure 8.8).
Economic indicators were strongly correlated with case fatality or mortality rate of indi-
viduals. Indian population has secured a highest eigenvalue, and communalities on age
group (50–60 years), lack of use of masks, irrespective of age, organizing/attending ritual
conferences, lack of social distance, travel history, opportunistic infections after COVID
treatment, comorbidity, ignorance of COVID-19 policy, and unvaccinated population have
a higher probability of contracting COVID-19 in the absence of preventive measures com-
pared to other studies reported at global level (Shiina et al., 2021). These differences in the
perception of pandemic crisis were due to the lack of public awareness, lack of literacy, low
level of socioeconomic status, and poverty, including the delayed application of precau-
tionary measures by the government authorities. Approximately 70% of population will
be facing financial difficulties. It may also play a pivotal role in exposed population. They
were experiencing a low level of self-esteem to deal with the pandemic, as quarantine
causes an economic burden on majority of the population who work for the daily require-
ments of food and shelter. In addition to above all, some people were unable to purchase
30
E c o n o m ic 25
56
20
48
H e a lth
2 40
4
6
8
S o c ia l p o lic y
FIGURE 8.8
Magnitudinal differences of risk factors in relation to economy.
goods for taking precautionary measures, including a detergent, a soap, gloves, and masks
for the whole family, which may pose an additional monetary burden on the exposed and
unexposed population, generally we noticed worse financial status in poor population
and low government subsidy for purchasing food items.
8.5 Conclusions
Risk assessment is a powerful tool that provides a rational framework for designing and
managing infectious and non-infectious diseases (e.g., SARS-Cov-19). The process of risk
assessment requires suitable statistical methods or tools to explore the factual base and
define the likelihood of adverse effects of pandemic on the quality of life of people. This
study used a practical approach to the identification and characterization of various risk
factors by new intervention models of risk-oriented augmented model. This model is able
to categorize the qualitative data sets and transform them to quantitative form to preclude
the percentage of risk of various attributes. The demonstrated model is more robust, and
researchers can easily adopt it in their research to mitigate any kind of risk based on the
objective of interest. This study is well defined for the assessment of risk of COVID and
can provide a rational basis for safe practices, management, and behavior aspects for the
implementation of healthy and safe preventive measures to control the COVID pandemic.
References
Barceló J., Sheen G.C.H. Voluntary adoption of social welfare-enhancing behavior: Mask-wearing
in Spain during the COVID-19 outbreak. PLoS One 2020; 15: 0242764. doi: 10.1371/journal.
pone.0242764.
Heydari S.T., Zarei L., Sadati A.K., Moradi N., Akbari M., Mehralian G., et al. The effect of risk com-
munication on preventive and protective behaviours during the Covid-19 outbreak: Mediating
role of risk perception. BMC Public Health 2021; 21: 54. doi: 10.1186/s12889-020-10125-5.
Hamer M., Kivimäki M., Gale C.R., Batty G.D. Lifestyle risk factors, inflammatory mechanisms,
and Covid-19 hospitalization: A community-based cohort study of 387,109 adults in UK. Brain
Behav Immun 2020; 87: 184–187. doi: 10.1016/j.bbi.2020.05.059.
Iavicoli S., Boccuni F., Buresti G., Gagliardi D., Persechino B., Valenti A., et al. Risk assessment at
work and Prevention Strategies on Covid-19 in Italy. PLoS One 2021; 16(3): 248874. doi: 10.1371/
journal.pone.0248874.
Lustria M.L.A., Noar S.M., Cortese J., Van Stee S.K., Glueckauf R.L., Lee J. A meta-analysis of web-
delivered tailored health behavior change interventions. J Health Commun 2013; 18: 1039–1069.
doi: 10.1080/10810730.2013.768727.
Mendoza-Jiménez M.-J., Hannemann T.-V. and Atzendorf J. Behavioral risk factors and adherence to
preventive measures: Evidence from the early stages of the Covid-19 pandemic. Front. Public
Health 2021; 9: 674597. doi: 10.3389/fpubh.2021.674597.
Meader N., King K., Moe-Byrne T., Wright K., Graham H., Petticrew M., et al. A Systematic Review
on the Clustering and Co-occurrence of Multiple Risk Behaviours. BMC Public Health 2016; 16:
657–66. doi: 10.1186/s12889-016-3373-6.
Muto K., Yamamoto I., Nagasu M., Tanaka M., Wada K. Japanese Citizens’ behavioral changes and
preparedness against Covid-19: An online survey during the early phase of the pandemic. PLoS
One 2020; 15: 0234292. doi: 10.1371/journal.pone.0234292.
Noble N., Paul C., Turon H., Oldmeadow C. Which modifiable health risk behaviours are related? A
systematic review of the clustering of smoking, nutrition, alcohol and physical activity (SNAP)
health risk factors. Prevent Med 2015; 81: 16–41 doi: 10.1016/j.ypmed.2015.07.003.
Patanavanich R., Glantz S.A. Smoking is associated with Covid-19 Progression: A Meta-analysis.
Nicotine Tobacco Res 2020; 22: 1653–1656. doi: 10.1093/ntr/ntaa082.
Reddy R.K., Charles W.N., Sklavounos A., Dutt A., Seed P.T., Khajuria A. The effect of smoking on
Covid-19 severity: A systematic review and meta-analysis. J Med Virol 2021; 93: 1045–1056. doi:
10.1002/jmv.26389.
Rosenstock I.M. The health belief model and preventive health behavior. Health Educ Monogr 1974; 2:
354–86. doi: 10.1177/109019817400200405.
Raudenbush S.W., Bryk A.S. 2002. Hierarchical Linear Models: Applications and Data Analysis Methods.
Thousand Oaks: Sage.
Shiina A., Niitsu T., Kobori O., Idemoto K., Hashimoto T., Sasaki T., et al. Perception of and anxiety
about Covid-19 infection and risk behaviors for spreading infection: An international compari-
son. Ann Gen Psychiatry 2021; 20: 13. doi: 10.1186/s12991-021-00334-6.
Tamara A., Tahapary D.L. Obesity as a predictor for a poor prognosis of Covid-19: A systematic
review. Diabetes Metab Syndr Clin Res Rev 2020; 14: 655–659. doi: 10.1016/j.dsx.2020.05.020.
Wang Q.Q., Kaelber D.C., Xu R., Volkow N.D. Covid-19 risk and outcomes in patients with substance
use disorders: Analyses from electronic health records in the United States. Mol Psychiatr 2021;
26: 30–39. doi: 10.1038/s41380-020-00880-7.
Yang J., Hu J., Zhu C. Obesity aggravates Covid-19: A systematic review and meta-analysis. J Med
Virol 2020; 93: 257–261. doi: 10.1002/jmv.26237.
9
Data-Driven Decision Support Model for COVID-19
9.1 Introduction
The SARS-Cov-19 crisis is an immense problem in the twenty-first century; not one country
is free from this deadly virus. It can spread at grassroots level and can seriously affect the
elderly population. As per the opinion of scientists, COVID is one of the killer diseases in the
history of pandemic diseases. Since January 2020, it affected globally the well-being of peo-
ple and many production sectors (industry, global economy, employment, food industry, etc.)
(Wang et al., 2020; Leung et al., 2020). So many preventive measures have been taken by coun-
tries to curb the spread of this disease in different geographical regions and to maximize the
economy in different sectors by allocating extra budget to individual sectors to revamp the
scarcity and necessary goods and products. However, in the realistic approach, the overall
quality of life of the affected population is submerged in the year of 2020, especially those
working in health sector, whose quality of life has shown to be worsened. The quality of life
domain of human being decreased below the global average. Many technological interven-
tions will be needed for the tuning of production sectors on health and for restoring the
quality of health domain-Human development index (HDI) to overcome the pandemic crisis.
This intervention could be simulated by massive data sets of various sectors. The presence of
massive data sets in different fields and real-world applications encourage the development
of data modeling and simulation techniques using artificial intelligence (AI), machine learn-
ing, and various stochastic convergence simulation techniques (Refisch et al., 2021). These
newer techniques aim to rediscover and extrapolate non-trivial information from massive
data sets of various databases of COVID-19 (Lau et al., 2021). These processes of analytical
study are the result of fundamental postulates of multidisciplinary research and advance-
ment of science at global level. It is mainly associated with COVID analytical research, viz.
drug development process, vaccination, and clinical trial at microlevel. This fundamental
surveillance model will support the advancement of applied mathematics, statistics, and
clinical science to develop separate algorithms based on the model simulation results. Most
importantly, the data-driven models will lead to a new era of data science and create numer-
ous data scientists by referring to academic and professional services on skill-based tech-
niques. However, clinicians and drug manufacturing companies who are thinking to solve
problems gain insights and knowledge to rediscover the causes and effects of SARS-Cov-19
from real databases. Currently, data-driven modeling approach is a more advanced field.
It is becoming more common in health sector, industrial management, and translation sci-
ences (Haug et al., 2020; Kermack et al., 1927). A data-driven model (DDM) was constructed
based on the real data sets of COVID-19, and we transformed the quantitative information
in mathematical form to analyze the parameters of interest; in particular, we demonstrated
system state variables (input, internal, and output variables) without explicit knowledge of
DOI: 10.1201/9781003204794-9 253

the clinical and epidemiological behavior of the disease. These methods represent the large
advancement of explicit and implicit knowledge. However, our conventional empirical mod-
eling techniques will support various applications of new algorithms, which mainly include
estimation of treatment effects on patients, patient care management, electronic database
management, and management of non-textual massive data sets of radiological blueprints
and their interpretation on radiological features. Practically, the DDM provides guidelines
for using data on team planning for patient care, logistics support, and management, solv-
ing ongoing problems such as admission, scarcity of beds, and oxygen supply. Basically, the
data-driven model can support clinicians and policymakers to solve the realistic problems
of COVID-19 without any overlapping information and also maintaining the overall well-
being of infected persons admitted in hospitals. In the case of health sector, many scientists
have already used this technique in decision support systems of robotic surgery, interactive
computer-based systems, and subsystems intended to help decisions makers. This technique
uses broad communication technologies such as data documentation, knowledge innova-
tions, or models to complete the decision-making tasks in the context of COVID pandemic.
A decision process support system presents COVID information including clinical and epi-
demiological findings. Typically, the DDM can provide decisive support for many applica-
tions of COVID management. It provides applications in the form of (i) access to all health
information, including epidemiological data and surge of COVID-19 waves, (ii) compara-
tive graphical representation, (iii) forecasted diagrammatic representation of new data or
assumptions, and (iv) consequences of different practical decisions on health system in a
specific context.
9.1.1 Communication-Driven Model
During any pandemic or infectious disease spread, communication is very important to
plan the policy, draft preventive measures, and provide guidelines to eradicate the disease
at population level. The CDM targets internal medical team, frontline healthcare work-
ers, and health professionals. It is one kind of cascade linkage model to disseminate and
transfer disease communication to public domain and WHO. Based on the above diffu-
sive model, our government authority incepts policy and control measures. Its purpose
is to help schedule different meetings of healthcare professionals in collaboration with
international organizations. The most common technology used to deploy the DSS is the
collection of epidemiological data and translation of real data into analytical form (disease
status, CFR, positivity rate in particular region, management of patients, etc.)
9.1.2 SARS-Cov-19 Data-Driven Model

Data are an integral part of planning and execution. They are the raw material for infec-
tious diseases and other research studies. Most of our data-driven models target com-
petent government authorities and policymakers for the implication of newer policies at
population level. It is deployed via a mainframe system of stratification, which is collected
from different strata such as province, district, tahsil, hobli, and panchayat. The lower
level is the village or hamlet in the selected region of low, moderate, and high prevalence
(infectivity is >60%). The DDM is a client–server model (authority/server link (data acces-
sory for policy)); for example, a computer is connected to a network of query systems of
individual regions to induct necessary prevention strategies based on the positivity rate.
The collected data should not be overlapping because it will make serious errors at the
time of data compilation and interpretation.
Data-Driven Decision Support Model 255
9.1.3 Document-Driven Model
A document is a sort of collection of information from patient bedside and epidemiologi-
cal and associated pathogenic factors. It is targeted at broad user groups (clinicians draw
clinical decisions; policymakers use implications of new health policies, and healthcare
professionals provide support for the arrangement of logistics (gloves, masks, sanitizer,
distribution of food, medicine, ambulance services, hospitalization, etc.)). This model is to
search or furnish full information and explore the necessary documents using specific set
of key words or search terms (Figure 9.1).
9.1.4 Knowledge-Driven Model
The knowledge-driven model is a network hub for the dissemination of SARS-Cov-19
information through advertisements and publicity of disease symptoms and causes of
deaths. Mainly, it is concentrated on a broad range of COVID care systems through printed
materials or via electronic app and newspapers. A knowledge-driven model clearly envis-
ages the overall perception, cause and effect relation of the pandemic disease, etc. It is
essentially used to provide management advice or to choose products/services. The typi-
cal deployment technology used to set up such systems could be the client–server system.
9.1.5 Model-Driven Decision Support System

It is a more complex system. The real data are transformed in mathematical derivation or
equations to choose all data sets at population level. The MDDS system helps in making
accurate decisions about disease stage, vaccination, survivability, mortality, and nursing
care of the affected population. These are used by competent authorities and policymakers
for the implementation of health policies and developmental programs for exposed and
unexposed population. Based on the simulation results or findings, experts who interact
with the policymakers for various purposes depend on how the model is constructed and
its reproducibility, accuracy, and decision analyses for pandemic crisis. These DSS can be
deployed with the help of mathematicians, statisticians, and researchers by stand-alone
publications of policy papers submitted to the competent authority (Figure 9.2).
Modelling
•Preventive
•COVID-19 Communication measures
driven DSS •Document driven
•Advertisement-
DSS
•Knowledge driven Feedback
Targeted COVID and data DSS
frontline helath team Health Policy
FIGURE 9.1
Flowchart of SARS-Cov-19 data-driven model.
9.2 Model formulation

Actual observed output (Y)
X1X2.. Xn Modelled (Real
Input data Learning is aimed at COVID system)
Minimizing this difference
Predicted Output ‘Y’
AI, Machine
learning neural
network or data
driven model
FIGURE 9.2
Decision support model flowchart.
Let x1, x2, x3…xn be random variables which are distributed with parameters λ > 0. The
probability density function (PDF) is as follows, where X1 = the number of positive cases of
SARS-Cov-19 as of July 27, 2021; X2 = the number of recovered cases; and X3 = the number of
death cases recorded at the end of the second wave (Figure 9.3).
 θ expo−θ x x≥0
f ( x1 , x2 , x3 , xn , θ ) =  (9.1)
 0 <x<
b
1 1  1 1
E ( x) =
θ
Var ( x ) = 2 ; σ 2 =
θ ∫  x − θ  θ expo
0
−θ x
=σ =θ =
θ
(9.2)
Surface Plot of Death vs Recovered, Positive
6 00 00 0
400 00 0
D e a th
200 00 0
3 00 00 000
0 20 0 0 0 0 0 0
10 00 000 0 R e c o v e r e d
0
10 00 000 0 0
2 00 00 000
30 00 000 0
P o s itiv e
FIGURE 9.3
Schematic of plan diagram of the model.
Total number of dies

θ=
Total number of recovered
9.2.1 Rayleigh Distribution
− x2
x
σ > 0 X ∈( 0, ∞ ) ; Probability density function PDF = 2 expo 2σ
2
(9.3)
σ
− x2
π
1 − expo 2σ 2 ; Mean = σ
2
9.2.2 Levy Distribution
c
µ = 1.75 C = 2.00 x = 120; PDF = * expo – c/2 ( x − µ ) ( x − µ )3/2 (9.4)
2π
9.2.3 Pareto Distribution
θ k2
Scale k > 0 θ > 0; k ( k , ∞ ) ; f ( x) = For x ≥ k (9.5)
xθ + 1
θ
 k
1 −   for x ≥ k ; ∞ for θ ≤ 1
 x
9.2.4 Laplace Distribution
1  x −θ  1  x −θ 
f ( x) = expo  – ; CDF = expo  (9.6)
2s  s  2  S 
Mean θ ; variance 2S2

Location θ ∈ R Scale > 0 ( x − ∞ , ∞ )
9.2.5 Gamma Distribution
1
k > 0 Scale θ > 0; f ( x) = x k −1x −1/θ (9.7)
Γ ( k )θ k
Mean kθ ; variance = kθ 2
9.2.6 Logarithmic Distribution
1 Pk
P ∈( 0, 1) k ∈( 1, 2, 3 n) ; Probability mass function = *
ln ( 1 − p ) k
β ( P, K + 1, 0 )
CDF = 1 + ; P = 0.74 k = 120 (9.8)
ln ( 1 − P )
9.2.7 Burnt Finger Poisson Distribution

This is an advanced probability distribution and can be used to determine the total num-
ber of COVID incidents that may occur in a period under the following conditions. At
the inception of the period, the COVID incidents may occur according to a Poisson pro-
cess with mean λ1; if a COVID incident does occur, then subsequent incidents may occur
according to a Poisson process with mean λ2 ; λ2 ≤ − λ1. This type of situation occurs when,
for example, an individual has an expected rate of infection λ2 , but if an infection occurs,
then the individual will become more careful (his/her “fingers got burned”) so that for the
rest of the modeled time a new, lower expected accident rate applies.
1
λ2 x − 1 λ1θ − λ2
∫
x−1
f ( x) = expo− ( λ2 − λ1 )t(1− t ) dt (9.9)
( x − 1)! 0
λ1 > λ2 ; λ2 > 0; x ( 0, 1…. + ∞ )
 λ 
 λ1 
(
λ 2 +  1 − 2  1 − e − λ1 = µ ) (9.10)
9.2.8 Skellam (λ1, λ 2) Distribution

A Skellam distribution is a discrete value between ( −∞ , +∞ ). This has a unique property
among discrete distributions. Usually, the model will explore the differences between two
independent Poisson distributed variables as follows: Skellam (λ1, λ2) = Poisson (λ1) − Poisson
(λ2). It can be used to model a series data of COVID spread between two geographical loca-
tions, e.g., India and global data sets.
x
f ( x ) = expo − λ1 + λ 2  λ1  2
(
 λ  I x 2 λ1 λ2
2
) (9.11)
λ1 > λ2 ; λ2 > 0; x ( −∞1; 0, 1…+ ∞ )
Mean = λ1 − λ2 ; variance= λ1 + λ2
Here, I x = Bessel function.
9.2.9 Reciprocal Distribution
The distribution is a right-skewed distribution and takes values between min and max.
If min and max are almost equal, the distribution is like a triangle (min, mode, and max).
The greater the ratio max/min, the more the distribution takes on a skewed form. For
example, COVID data series at inception level and maximum point or peak level are con-
sidered for model construction.
1
f ( x) = (9.12)
xq
where q = Log(max) − Log(min)
Log ( x ) − Log ( min )

F ( x) = ; 0 < min < max
q
Max − Min
Mean =
q
( Max − Min )  Max ( q − 2 ) + ( q + 2 )

Variance =
2q2
9.2.10 Maxwell–Boltzmann (MB) Distribution

The MB distribution describes the rate of change of SARS-Cov-19 virus density that
spreads the infection in any type of mode (air, water, objects, etc.), where the virus does
not constantly spread and interact with the environment at each point of time, but freely
move from one place to another. The “α” parameter only changes the scale. The distribu-
tion always has the same shape. The distribution is the magnitude of a three-dimensional
vector whose components are independent and normally distributed with mean 0 and
standard deviation.
Maxwell of virus density ( a) = Normal ( 0, a ) + Normal ( 0, a )

2 2
(9.13)
Maxwell of virus density (a) = χ 2 * a
9.2.11 Inverse Gaussian Distribution

The inverse Gaussian distribution is a right-hand skewed distribution bounded at zero
points; the inverse Gaussian distribution is seldom used in the estimation of spread of
infectious diseases through Brownian principles. In case of skeweness, the Inverse
Gaussian distribution tend to lognormal distribution. The log-normal distribution has too
heavy right-hand tail, which can estimate the disease rate of process.
λ  λ ( x − µ )2 
PDF = Expo  −  (9.14)
2 πx 3  2µ 2 x 
µ > 0, λ > 0, x > 0
µ3
Mean = µ; variance =
λ
9.2.11.1 Model Results
The exponential distribution was employed to predict the future values when we use
sufficient COVID data series with a relatively low infectivity and death rates are expo-
nentially distributed in the second wave of SARS-Cov-19. However, uncertainty is high
due to emplaning (go or put on board an aircraft) and lack of logistic supports to fight
against the pandemic disease. As we learnt more about the virus and our reaction to it,
we can visualize the death rate by exponential smoothing modeling techniques based
on the convergence of probability values p ( X ≥ x ) and the parameters remained constant
with larger population. Death cases have the projected parameter “θ ” with varying popu-
lation size; initially, the parameters were fixed as 1.75 with 120 million population. The
projected variance was 0.573, and the SD was 0.327. A similar process was continued to
flatten the normalcy of cases and death rate (Table 9.1). The results found that normalcy
begins from parameter value 3.00 with the infected population of 170. The projected fig-
ure was 0.095, followed by varying probability 3.50 and 3.75. The standard deviation was
ignorable, and normalcy drew up asymptomatically. This model typically provides a wide
range of estimation of normalcy based on available data sets of COVID-19, and also we
projected a number of deaths as certain in the surge of COVID-19. Models will be used to
change the behavior of data series. The projection point is very easy and more familiar for
scientists who make broad recommendations to formulate policy decisions at the time of
early infectivity. Similarly, this projected model has changed attitude and behavior of data
series and also supports decision-making interventions. We followed the same procedure
to demonstrate the Weibull distribution model: the model projected failure rate with scale
parameter “α ” and shape parameter “β ”. As per the model output, the failure rate started
in α = 3.00 and β = 4.50 and X = 170. From the model output, results show the death rate
was reached at the rate of 2.13%–2.59%. However, the death rate cannot cross the limiting
value of 2.59% in the second wave at population level (Table 9.2).
During SARS-Cov-19 infection, the hospitalization and mortality rate curve was ampli-
fied by the 3D surface plot (Figure 9.4). A total of 3 million people were infected in the first
and second wave of the outbreak. The recovery rate was significantly correlated at the rate
of 85%–90%, and the average CFR was 2.10%–2.59%. It indicates that more people eventu-
ally deviated from following social distancing; they either ignore or heed safety warnings,
partially or completely. Individual choices depend on a variety of factors such as age, soci-
etal values, and economic necessity to work among others. New cases drew an infectivity
TABLE 9.1
Variation of Death Rate Flattens Based on p ( X ≥ x )
p( X ≥ x )
Characteristics θ -Parameter x-Millions E(x) Var ( x ) σ2

Death cases 1.75 120 0.576 0.573 0.327
2.00 130 0.503 0.502 0.256
2.25 140 0.445 0.443 0.198
2.50 150 0.407 0.402 0.161
2.75 160 0.334 0.336 0.114
3.00 170 0.308 0.308 0.095
3.25 180 0.289 0.286 0.082
3.50 190 0.267 0.261 0.071
3.75 200 0.252 0.255 0.063
TABLE 9.2
Death Rate Flattens Based on p ( X ≥ x ) from the Weibull Model
p( X ≥ x )
Characteristics Shape Parameter x-Millions Scale E(x) Var ( x ) σ2

Death cases 1.75 120 2.0 1.782 1.05 1.10
2.00 130 2.5 2.21 1.15 1.34
2.25 140 3.0 2.65 1.24 1.56
2.50 150 3.50 3.10 1.32 1.76
2.75 160 4.00 3.55 1.39 1.95
3.00 170 4.50 4.00 1.46 2.13
3.25 180 5.00 4.48 1.51 2.29
3.50 190 5.50 4.94 1.56 2.45
3.75 200 6.00 5.41 1.61 2.59
rate of up to 45%–65%, and an increased trend was seen in different countries, including
India, disease spread had the intended effect of reducing deaths in some of the countries
and also, perversely, made the original prediction seem realistically a true projection of
data points from our model; therefore, smoothening of the model will project the accurate
points of infection, death, and recovered cases in massive data sets. However, in a realistic
approach, many countries attempted to control the fast rising number of SARS-Cov-19
positive cases and deaths. During the process of diseases outbreak, many challenges are
faced by health care workers, one of the most important factor derived to control of dis-
eases is prevention measures. The deviation from prevention measures did not flatten the
curve in Indian states, including some countries. It has taken on pandemic proportions.
In the absence of significant control measures, the curve does not ascent steeply with the
number of cases growing exponentially distributed in the second wave of pandemic. In
fact, this level of proliferation was experienced in the USA, India, the UK, and Brazil and
closely follows an exponential trend.
According to the second wave perception, an insight surveillance of data sets of second
wave in India clearly depicts that the upper control limit of death was estimated at 40,238
with mean 19,604 and the lower limit was 1,031. The death cases were estimated by X-bar
and R chart, and infection was 464,863 per day with an average of 340,129 (Figure 9.5). The
lower limit was 215,396. Asymptomatic, presymptomatic, and asymptomatic infectious
persons can infect the healthy population susceptible to SARS-Cov-19. More importantly,
various database reports and analyses indicate that the number of asymptomatic cases
was many times higher than the reported symptomatic cases worldwide.
• Regression with life data: positive versus death

• Response variable: positive
• Frequency: recovered
• Censoring information count
• Uncensored value: 175067121
• Estimation method: maximum likelihood
• Distribution: Weibull
• Relationship with accelerating variable(s): linear.
Weibull distribution model is widely used to describe the different types of observed
failure components and logical phenomena of infectious diseases. Mainly, it is used in
reliability and survivability analysis. In addition to the traditional two-parameter and
three-parameter Weibull distribution models, a related distribution is constructed based
on the available data sets of COVID-19. Currently, two parameters are used to construct the
model settings. The purpose of this model is to describe the failure rate of infection, which
mainly emphasizes the infectious mechanisms that have the potential for further applica-
tions. After introducing the traditional Weibull distribution, some historical developments
and basic analytical properties are used to describe the present status of pandemic crisis.
As per the model output, the infection rate positively moved and the coefficient was 14.61
(p = 0.000) with a lower limit of 14.61–15.86 at a growth failure rate of 1.74. We have consid-
ered the scale parameters for further prediction approach (Table 9.3 and Figure 9.6).
Lord Rayleigh, an English scientist, invented a continuous probability distribution for
solving the real-world problems of engineering—medical image magnetic resonance
paths of dense scattered signals reaching a receiver. In the case of physical science estima-
tion of wind speed, wave light and sound light radiation are the prime traits to forecast the
wind speed. In case of humanbeing, the measurement of lifetime of an object with respect
to age-specific parameters were considered for the formulation of model, etc. Figure 9.5
TABLE 9.3
Regression Model Output
Standard 95.0% Normal CI
Predictor Coeff. Error Z P Lower Upper

Intercept 14.6158 0.0000771 1,895 64.83 0.000 14.6156 15.8659
Death 0.0000052 0.0000000 231 17.03 0.000 0.00052 1.523
Shape 1.74702 0.0001080 1.74681 1.74723
Log-likelihood = -2930996335.786.
Xbar-R Chart of Death

D e a th
40000 U C L= 4 0 2 3 8
30000
Sample M ean
__
20000 X= 19604
10000
0 LC L= -1 0 3 1
1 2 3
S a m p le
D e a th
1
600000
450000 U C L= 4 6 4 8 6 3
Sample Range
_
R = 340129
300000
LC L= 2 1 5 3 9 6
150000
0
1 1
1 2 3
S a m p le
FIGURE 9.4
Distribution of SARS-Cov-19 positive, recovered, and death cases.
P r o b a b ility P lo t o f P o s itiv e , R e c o v e r e d , D e a th
E x p o n e n tia l - 9 5 % C I
9 9 .9
99 V a r ia b le
90 P o s itiv e
80 Reco v ered
70
60 D e a th
50
40
30 M ean N A D P
20 949463 203 14 3.75 3 < 0.00 3
862400 203 15 2.81 6 < 0.00 3
Percent
10
19604 203 17 9.35 9 < 0.00 3
5
3
2
1
0 .1
1 10 0 00 0 00 00 00 00
10 10 00 00 00 00 00
10 10 0 0 0
10 1 00 00
10
Data
FIGURE 9.5
Quality control (QC)—X bar and R chart of SARS-Cov-19 death rate.
FIGURE 9.6
Exponential distribution of SARS-Cov-19 death rate.
shows the lifetime of infection rate of COVID in a high pandemic zone. The shape param-
eter “σ ” was <1 = 0.063, and the results were correlated. The infection rate would be declin-
ing from day 200 onward (Figure 9.7).
Vilfredo Pareto (1848–1923) proposed the Pareto distribution. It was depicted that Nx
number of people were infected by COVID at the early stage of pandemic. As “x” can be
modeled as a power law function, a power law is a theoretical empirical relationship gov-
erned by a power function. In case of geometry correlation of polygon length and squares
FIGURE 9.7
Rayleigh probability distribution.
of each side is articulated, the population density in ecology (inequality parameter close
to 1) because observation show the heterogentity. We used regular data sets of COVID-19
considering base infection and random variate X = 120 and Nx values. The model clearly
converges when the inequality parameter is >1, i.e., equal to 5. That means five people
would be infected at the rate of 120 per minute globally (Figure 9.8).
The Laplace distribution is a continuous distribution bearing two parameters; we have
estimated the differences between two independent variates with identical exponential
distributions. The Laplace distribution is also called the double exponential distribution.
For location parameter “μ” and scale parameter “σ”, it is defined by the probability den-
sity function. Figure 9.9 shows the distribution of Laplace of COVID data series; the scale
parameter is > 1, i.e., 2.75, and s = 4. A total of 2.75 times infection growth was geometrically
progressed in high prevalence states.
Gamma distribution is another widely used distribution. Its importance is largely due
to its relation to the exponential trend of COVID data series and normalcy. Here, we have
projected a variation of gamma distribution Γ ( x ), which is an extension of factorial func-
tion to real and complex numbers; specifically, we have predicted based on the time variant
of the real number of COVID-19, n ∈( 1, 2, 3, 4 n). The model is widely applied in different
fields of science to forecast continuous variables that are always positive and have skewed
distribution. It occurs naturally in the process where the waiting times between events are
relevant. As per the model results, the average rate of infection transmitted to others is 5.0
per person (Figures 9.10 and 9.11).
A log-normal distribution is normally distributed logarithmic values with low mean
values and larger variance, and all positive values often fit this type of distribution in
FIGURE 9.8
Pareto probability distribution.
FIGURE 9.9
Laplace distribution.
infectious diseases. The values must always be positive integer as log(x) exists only for pos-
itive values of “x”. As per the model output COVID data series, 74.0% infection occurred in
the second wave of infection; approximately 120 million population would be infected in
the surge of COVID-19 wave (Figure 9.9). In the case of Burnt Finger Poisson distribution,
we consider the mean infection value of both global and national levels. Our model clearly
FIGURE 9.10
Gamma distribution.
FIGURE 9.11
Logarithmic distributions.
depicts that the 50% infection attitude in the 10-month time period can be compared to the
national level infection rate of 30% (Figure 9.12). The same variation was found in Skellam
(λ1, λ2) distribution (Figure 9.13).
FIGURE 9.12
Burnt Finger Poisson distribution.
Clinical Confirmataory
WHO,
attributes ,
Data Competent Information Facts data sets
epidemiological obtained
authority patient record
Level of improvements on DSS
FIGURE 9.13
Decision support model flow chart.
9.3 Bayesian Decision Support Data-Driven Model (BDSDM)

The Bayesian support network decision model is a probabilistic graphical method consist-
ing of directed acyclic and acyclic network graphs: DAG (direct acyclic network graphs)
and cDAG-child (direct acyclic network graphs). This denotes dependencies and inde-
pendencies between variables, and conditional probability matrix of table obtained from
original SARS-Cov-19 data series. Each variable depends on nodes in the BN and has a set
of states, and the probability of each state of nodes is dependent on the states of the parent
nodes and linked with many child nodes. We considered secondary data sets of COVID—
the number of cases infected, relapsed, recovered, symptoms duration, comorbidity, and
different clinical traits—for the construction of BN model. Prior and posterior probabili-
ties were obtained from the original data itself (normalcy assumptions were considered).
Qualitative data sets such as yes or no symptoms, gender, exposed and unexposed, and
masks–without wearing masks were derived from the clinical and epidemiological set-
tings. Secondary data were collected from WHO and COVID-19 Worldometer virtual
TABLE 9.4
Bayesian Decision Support Model
Characteristics P(H) P(D|H) P(D|H′) P(H|D) Odds Likelihood (L 0) Interpretation
Overall clinical attributes 0.52 0.36 0.21 0.65 1.08 1.71 Significance
Fever 0.84 0.23 0.45 0.72 1.85 12.36 Significance
Cough 0.65 0.42 0.28 0.73 2.84 1.49 Significance
Body pain 0.74 0.55 0.65 0.70 2.64 1.22 Significance
Loss of smell and taste 0.43 0.65 0.28 0.61 1.49 5.32 Significance
Mean duration of 4 days 0.33 0.74 0.32 0.53 1.19 2.38 Significance
at the onset of symptoms
On-time hospitalization 0.16 0.22 0.45 0.08 0.12 <1 Insignificance
Oxygen level >95% 0.11 0.32 0.16 0.198 0.63 0.73 Insignificance
Comorbidity 0.87 0.45 0.26 0.92 4.55 1.14 Significance
Recovered 0.82 0.55 0.48 0.83 0.20 2.75 Significance
Relapsed 0.17 0.24 0.32 0.13 0.38 0.45 Insignificance
Deaths 0.28 0.10 0.22 0.15 1.44 0.35 Insignificance
Economic feasibility for 0.60 0.56 0.16 0.84 2.36 3.21 Significance
hospitalization
Preventive measures 0.78 0.45 0.24 0.86 3.54 0.87 Insignificance
TABLE 9.5
Spike Protein Variants of COVID-19
Spike Protein Variant Tong Dock A Binding Affinity,
ACE2 Tong Dock A Docking Score Cluster Size ΔG (kcal mol−1)
Reference 1,262.964 34 −13.4
B.1.1.7 1,293.348 36 −12.8
B.1.351 1,447.344 32 −16.4
B.1.617 1,541.675 39 −16.2
platform. Clinical data sets were collected from COVID care centers. The following BN
model was constructed based on the standard approach, and also pooled network DAG
and cDAG probabilities were correlated. The likelihood (L0) was estimated. Interpretation
was done based on likelihood ratio, and odds values were estimated (Tables 9.4 and 9.5).
P ( H |D ) =  P ( D|H ) P ( H )  /  P ( D|H ) P( H ) + P ( D|H ′ ) ( 1 − P( H )) 
• H = the hypothesis; in this case, H is the hypothesis that the population is exposed to
SARS-Cov-19 and H′ is the hypothesis that the population is not exposed to the virus.
• D = the datum; in this case, D is the SARS-Cov-19-positive test result.
• P(H) is the prior probability to be infected by SARS-Cov-19, which was given in
the problem.
• P(D|H) is the probability of a positive test result to be obtained from the popula-
tion exposed to the risk of COVID. This is also called the hit rate and was given in
the problem.
• P(D|H′) is the probability of a positive test result to be obtained from the population
not exposed to COVID. This is also called the false rate and was given in the problem.
9.4 Discussion
Scientists understand the dynamism of disease of SARS-Cov-19 through the mathematical
and statistical lens of modeling techniques. The field of intervention is elusive, but it yields
significant results for policy decision support. Within 1.5 years, the SARS-Cov-19 outbreak
has made a significant loss in the production sector, depleted the quality of life of people,
and also reduced the human development index at global level (Lau et al., 2021; Liu et al.,
2019; Refisch et al., 2021). Approximately 20 million reported positive across 273 countries
(as of the end of January 2022), with 3.5-5.5 million deaths estimated worldwide. Unlike
any other disease in history, COVID has generated an unprecedented volume of data as
compared to Spanish flu and other pandemic diseases (Liu et al., 2021; Nisioti et al., 2021;
Pekpe et al., 2021). The massive data sets of COVID-19 can rigorously support decision sup-
port drive for health policy, vaccination campaign, clinical and nursing care of affected
population, and also drug manufacturing process. The scientists and WHO have continu-
ously updated the data sets of COVID, which are broadly available to the general public.
Nowadays, analytical interventions of AI and machine learning supporting mathematical
model are very important to boost the entire policy system worldwide. It can play an
important role in providing quantitative insights into the COVID-19 in macro- and micro-
levels. The decision support analytical model is an ongoing and debatable issue in health
policy sector because of management of patients in poor resource setup, varying treatment
modalities with respect to different geographical locations in association with genetic
variant virus, reduced rate of CFR at population level. Mainly, we should concentrate on
the improvement of quality of life of the affected population through socioeconomic, pol-
icy, and overall well-being support to the affected population. In the present study, we
have explored and formulated different types of advanced modeling techniques of COVID-
19 real-world problems; the insight analytical model will smoothen the entire system and
provide support to develop data decision support for machine learning and AI (Roosa et al.,
2020; Tuite et al., 2020; Verschuur et al., 2021; Viner et al., 2020). We highlighted the early suc-
cess and merits of models to describe the various clinical settings of data sets to predict the
tenable projection points and significance of various structural and unstructured series of
data through real probability values of naive Bayesian probability models. We formulated
the modeling for COVID-19 based on prior knowledge and numerous assumptions.
Additionally, we systematically approached the numbers of positive cases, recovered, and
COVID-induced death cases of massive data sets used to construct the model settings. An
adjustment to the data sets was made to fit the current knowledge on the SARS-Cov-19
behavior. The BN and probability distribution were demonstrated with varied settings
and were optimized using Monte Carlo simulation techniques. Our model shows that
clinical attributes such as fever, cough, body pain, and loss of smell are significantly cor-
related and their likelihoods were >100%. The mean duration of hospitalization is 4 days
with the onset of first symptoms (Haug et al., 2020; Kucharski et al., 2020; Khailaie et al.,
2021). In the affected population having one or more underlying comorbid conditions, the
recovery rate was strongly correlated to lower level of symptoms. The CFR was less com-
pared to Spanish flu and plague pandemics. The structure of data-driven model is built on
a combination of theoretical and practical postulates, and we empirically collected data
sets. In this context of both liability of knowledge and novelty of the epidemiological view,
the potential approach to taking maximum epochs of data compilation with attenuated
existing data was also highlighted even if they may be partial or incomplete. Thus, with
maximum information webbed by DAG and cDAG, the pooled values show more augmen-
tation of disease spread in the first and the second wave of SARS-Cov-19 disease. As per
this analysis, we have formulated decision-framed inherent knowledge obtained from the
COVID data series (Guan et al., 2021; Hsu and Hsieh, 2005; Hernandez-Matamoros et al.,
2021; Hellewell et al., 2020). The model input shows the possible ways to identify the impor-
tant correlations between the knowledge of disease spread and compartments that are
then used to determine the disease transmission pattern and how the disease biologically
affects at population level. Pooling of all clinical variables empirically collected from the
inception of COVID has converged good results, and that may support public health deci-
sion making at an early stage of geometric progression of the disease. Nevertheless, as a
result of model output, we recall the modeling approach; scientists’ proposal makes it pos-
sible to better portray the changing dynamics of the epidemic according to collective con-
trol measures decided by the local authorities (De Bruin et al., 2020; Ellul et al., 2015;
Gaglione et al., 2008). The inner practical methodological aspects are that of newer tools to
explore the outbreak measures and epidemiological relation between diseases and also to
identify path physiological network of disease pandemic and causatives at larger extent.
Furthermore, our important approach is also to describe the databases in combination
with partial available knowledge at the time of model construction. Finally, the present
advanced modeling technique does not only endeavor to address the salient characteris-
tics of diseases, but also addresses various challenges and issues confined to economics,
management of cases in risk situation, control measures, and vaccination drive at popula-
tion level. It has also anticipated the possibility of relapse of SARS-Cov-19 or some of its
various lineages, a projection that was not common in real data sets. A projection point of
disease progression that was a complex phenomenon and derived longer term of hypoth-
esis because, diseases are upstream, modeling strategies are more complex as compared to
other pandemic diseases, many patients had claimed and opportunistic infection after
COVID treatment taken (Wu et al., 2020; Wang et al., 2020). Now, the intervention of oppor-
tunistic infection claims a longer hypothesis, but it was a substantial result of several stud-
ies in the span of 2020–2021. While the decision support adoptive model was powered to
provide accurate predictions by using massive data sets, the predictive model has the abil-
ity to predict different disease convergent points and policy intervention herein may be
longer depending on the duration of dynamical stable phases of the epidemic and ende-
mism of diseases at the early stage of infection. This model is more robust and may gener-
ate posterior and prior probabilities by the data itself and may be dynamically stable for
massive data compilation, since, in the meantime, the application of data-driven model can
weigh different factors and should pertain to handling the issue of recent data being more
accurate and valid than the earliest ones (Braca et al., 2021; Bock et al., 2008; Candido et al.,
2020; Contreras et al., 2021). Furthermore, substantial challenges of SARS-Cov-19 eradica-
tion will need real and accurate biological and clinical facts to describe the disease mecha-
nism and it mainly depends on the quality of the data used and the statistical approach
used for the interpretation of massive data. As such, the fact that our model’s analytical
strategies considered only the data collected would be the outcome of the present model
under the threat of potential errors in this data repository. A final limitation is associated
with the fact that our modeling has assumed structured and unstructured data sets. In
case of unstructured data, pooling and classification of data is a challenging task and takes
more time for reproducing the output of the model (Anastassopoulou et al., 2020; Blackwood
and Childs, 2018). A future work is required, in which new variables, e.g., causes of oppor-
tunistic infections, age-specific complications, and drug reaction contamination pattern of
COVID-19, would be considered using the present model strategy.
9.5 Conclusions
Summing the model outputs, the present study concludes that SARS-Cov-19 is a global
threat and scourge. The data-driven decision system model is very important in the pres-
ent scenario because we formulate health policy, logistic support, and patient care and
evaluate the clinical attributes of infected patients. In the above fascinating sense, our con-
structed model represents the specific form of control system that helps decision makers to
identify and solve the real problems of COVID-19, which makes complete decision process
tasks easier and draw non-trivial information from massive data. In this present research
work, we extracted big data series of COVID analysis and explored inherent knowledge of
model construction and how to use the model in the context of infectious disease for the
estimation of infection, death, and recovered rate at population level. In the advancement
of COVID decision support system, our constructed model will serve as an analytical and
clinical guide and provide methodological interventions for scientists, research beginners,
and postdoctoral researchers. Our formulated model would be used to solve the complex
analytical problems in SARS-Cov-19 pandemic.
References
Anastassopoulou C., Russo L., Tsakris A., Siettos C. Data-based analysis modelling and forecasting
of the Covid19 outbreak. PloS one 2020; 15(3): 21–39.
Blackwood J.C., Childs L.M. An introduction to compartmental modeling for the budding infectious
disease modeler. Lett Biomathe 2018; 5(1): 195–221
Braca P., Gaglione D., Marano S., et al. Decision support for the quickest detection of critical Covid-19
phases. Sci Rep 2021; 11: 8558.
Bock D., Andersson E., Frisén M. Statistical surveillance of epidemics: Peak detection of influenza in
Sweden. Biometrical J 2008; 50: 71–85.
Candido D.S., Claro I.M., de Jesus J.G., Souza W.M., Moreira F.R.R., Dellicour S., Mellan T.A., du
Plessis L., Pereira R.H.M., Sales F.C.S. et al. Evolution and epidemic spread of SARS-Cov-2 in
Brazil. J Sci 2020; 369(6508): 1255–1260
Contreras S., Dehning J., Loidolt M., Zierenberg J., Spitzner F.P., Urrea-Quintero J.H., Mohr S.B.,
Wilczek M., Wibral M., Priesemann V. The challenges of containing SARS-CoV-2 via test-trace-
and-isolate. Nature Commun 2021; 12(1): 378.
De Bruin Y.B., et al. Initial impacts of global risk mitigation measures taken during the combatting of
the Covid-19 pandemic. Saf Sci 2020; 128: 112–117.
Ellul N., Capocchi L., Santucci J.F. Big data decision making based on predictive data analysis using
DEVS simulations. Proceedings of the 3rd ACM SIGSIM Conference on Principles of Advanced
Discrete Simulation June 2015: 257–258.
Gaglione, D., et al. Adaptive Bayesian learning and forecasting of epidemic evolution data analysis
of the Covid-19 outbreak. IEEE Access 2008; 8: 175244–175264.
Guan D., et al. Global supply-chain effects of Covid-19 control measures. Nat Hum Behav 2020; 4:
577–587.
Hsu S.B., Hsieh Y.H. Modeling intervention measures and severity-dependent public response dur-
ing severe acute respiratory syndrome outbreak. SIAM J Appl Math 2005; 66(2): 627–647.
Hernandez-Matamoros A., Fujita H., Hayashi T., Perez-Meana H. Forecasting of COVID19 per
regions using ARIMA models and polynomial functions. Appl Soft Comput J 2021; 96: 1–14.
Hellewell J., et al. Feasibility of controlling Covid-19 outbreaks by isolation of cases and contacts.
Lancet Glob Health 2020; 8(4): 488–496.
Haug N., Geyrhofer L., Londei A., Dervic E., Desvars-Larrive A., Loreto V., Pinior B., Thurner S.,
Klimek P. Ranking the effectiveness of worldwide Covid-19 government interventions. Nat
Hum Behav 2020; 4(12): 1303–1312.
Kucharski A.J., Russell T.W., Diamond C., Liu Y., Edmunds J., Funk S., Eggo R.M. Early dynamics of
transmission and control of Covid-19: A mathematical modelling study. Lancet Infect Dis 2020;
20(5): 553–558.
Khailaie S., Mitra T., Bandyopadhyay A., Schips M., Mascheroni P., Vanella P., Lange B., Binder S.C.,
Meyer-Hermann M. Development of the reproduction number from coronavirus SARS-CoV-2
case data in Germany and implications for political measures. BMC Med 2021; 19(1): 32–34. doi:
10.1186/s12916-020-01884-4.
Kermack W.O., McKendrick A.G., Walker G.T. A contribution to the mathematical theory of epidem-
ics. Proc R Soc Lond 1927; 115, 700–721.
Lau H., et al. Evaluating the massive underreporting and under testing of Covid-19 cases in multiple
global epicenters. Pulmonology 2021; 27, 110–115.
Liu J., et al. Data mining and information retrieval in the 21st century: A bibliographic review Comput
Sci Rev 2019; 34(11): 105–108.
Liu X.X., Fong S.J., Dey N., González Crespo R., Herrera-Viedma E. A new SEAIRD pandemic predic-
tion model with clinical and epidemiological data analysis on COVID-19 outbreak. Appl Intell
2021; 51: 4162–4198.
Leung C.K., Chen Y., Shang S., Deng D. Big data science on Covid-19 data. Proceedings of the IEEE 14th
International Conference on Big Data Science and Engineering (BigDataSE) 2020; 14–21.
Maier B.F., Brockmann D. Effective containment explains subexponential growth in recent confirmed
Covid-19 cases in China. Science 2020; 368: 742–746.
Nisioti A., Loukas G., Laszka A., Panaousis E. Data-driven decision support for optimizing cyber
forensic investigations. IEEE Trans Inf Forensics Secur 2021; 16: 2397–2412.
Pekpe K.M., Zitouni D., Gasso G., et al. From SIR to SEAIRD: A novel data-driven modeling approach
based on the grey-box system theory to predict the dynamics of Covid-19. Appl Intell 2021. doi:
10.1007/s10489-021-02379-2.
Refisch L., Lorenz F., Riedlinger T., Taubenböck H., Fischer M., Grabenhenrich L., Wolkewitz M.,
Binder H., Kreutz C. Data-driven prediction of Covid-19 cases in Germany for decision mak-
ing. medRxiv 2021; 3: 3–16.
Roosa K., Lee Y., Luo R., Kirpich A., Rothenberg R., Hyman J., Yan P., Chowell G. Real-time fore-
casts of the covid-19 epidemic in China from February 5th to February 24th, 2020. Infect Disease
Modell 2020; 5: 256–263.
Tuite A.R., Ng V., Rees E., Fisman D. Estimation of COVID-19 outbreak size in Italy. Lancet Infect Dis
2020; 20(5): 537.
Verschuur J., et al. Observed impacts of the COVID-19 pandemic on global trade. Nature Hum Beha
2021; 5(3): 1–3.
Viner R.M., et al., School closure and management practices during coronavirus outbreaks including
Covid-19: A rapid systematic review. Lancet Child Adolesc Health 2020; 4(5): 397–404.
Wu P., Hao X., Lau E.H.Y., Wong J.Y., Leung K.S.M., Wu J.T., Cowling B.J., Leung G.M. Real-time
tentative assessment of the epidemiological characteristics of novel coronavirus infections in
Wuhan, China, as at 22 January 2020. Euro Surveill 2020; 25(3): 2000044.
Wang C.J., Ng C.Y., Brook R.H. Response to Covid-19 in Taiwan: Big data analytics new technology
and proactive testing. JAMA 2020; 323(14): 1341–1342.
10
Age-Specific SARS-Cov-19 Incidence Modeling
10.1 Introduction
SARS-CoV-2 is one of the devastating diseases, and an approximately 3.5-5.5 million
population have lost their lives worldwide. Approximately 42.80 lakhs of population lost
their life worldwide (Sobotka et al., 2020; Sahin et al., 2020). Further, the estimation of
age-specific incidence is an essential analytical tool for policymakers for the implementa-
tion of health policy and for conducting induction studies on demographic transition and
population structure of the infected and general population. However, the global compari-
son on incidence rate is the independent effect of the age-standardized rate. This chapter
constructs a new model of age-specific incidence and mortality in association with various
clinical attributes. Newly, we emphasize the age-specific findings and correlation with
possible artifacts in the COVID-19 data sets (Yang 2020; Zhao et al., 2020a). This technique
will provide insights into the disease mechanisms at the sample level and can help to
magnify the effect on the worldwide population. Many studies clearly depicted that the
age-standardized prevalence rate is a conclusive summary of overall parameters of demo-
graphic and clinical interventions. The estimated rate would be observed components of
data sets. Our formulated model will become the full-blown epitome for reproducibility of
age-specific incidence and composition of the infected population (Monod et al., 2021; Khan
and Atangana, 2020; Kulu and Dorey, 2020). In other words, the observed age-specific rates
were applied (directly) to a theoretical standard population. Although the age specific cor-
related parameters will allow us to explore and standardize the world standard criteria for
estimation of disease at different geographical location, and also represented with neither
the inclusive nor the future age-specific global population considered. In this regard we
will switch to move the model formulation or development. More up-to-date standards
would be only worthwhile if they could provide health benefits that outweighed the pit-
falls of the constructed model. The model outputs will provide sufficient and efficient
information to researchers and clinicians for the accurate estimation of hazard risk rate,
expected cases of the standardized world population to be infected from the nCov19, etc.
Furthermore, it has been shown that very different absolute values on age-standardized
rates are obtained by using different standard limits. Our estimates of age-adjusted rela-
tive risk (aRR) are quite similar to the world standard, and the constructed model has no
complexity in the analysis of massive data sets of COVID-19 (Inaba, 1990; Iannelli and
Manfredi, 2007; Hethcote, 2000). Therefore, the main effect of study methodology has
changed the standard to a flare up-to-date increased trend that was shown in of the global
population infected from COVID-19 pandemic. It would produce consequential results
that the value of the age-standardized rate would be closer to that of the real values simu-
lated from the stochastic convergence mathematical simulation model. Accordingly, from
DOI: 10.1201/9781003204794-10 275

both theoretical and practical points of view, we develop advanced age-standardized sta-
tistical real models of the COVID-19 infectious disease. The main applications of the pres-
ent models are as follows:
i. To provide real postulates of the mechanism of virus spread across the globe and
help researchers in the consistent estimation of the number of cases, incidence,
and hazard risk of the larger population. It is one of the simplest techniques for the
estimation of crude death rate and age-specific incidence of COVID at the sample
as well as population level.
ii. To provide insights into the analytical steps for the estimation of death and inci-
dence parameters considering clinical attributes.
This model serves as a tool for clinicians and policymakers in the implementation of policy
worldwide.
E
CruderateCR = *K (10.1)
P
Where
E = the number of events
P = the midyear total infected population from COVID surge
K = the constant value, often 1,000 or 10,000.
The newer model showing the association of age-specific incidence with crude rate is as
follows:
 5
10 

∑ d  /  ∑ y   * CR = (10
i i
5
)
* 1270 / 1451646 × CR (10.2)
And the age-standardized rate is calculated using Table 10.1.
TABLE 10.1
Age-Specific Model Parameters
No. of Standardized World Expected Population
No. of Persons at Age-Specific Total Population Infected by Infectious
Age Group Cases Risk Incidence Weighted per 100,000 Disease
n
E = 105 di yi  * [ wi pi / di ]
(i) di yi 105 di yi
∑w p
i =1
i i
Age-Specific COVID-19 Incidence 277
10.3 Model Output
Equation (10.1) is linked with random state variables of X1, X2….Xn, persons infected at the
time, etc. The model will become
dx
= k − uX − β xy (10.3)
dt
dy
= Y ( k − uX − β xy ) (10.4)
dt
dy
= Y (β x − u − v) (10.5)
dt
β k
R0 = * (10.6)
µ+v u
R0 = the basic reproduction number.

I (the infected population of specific age group) × R0 = New Infection
∑I x * Ro = New infection (10.7)
The spatial distribution of COVID-19 transmission is calculated by using
Spatialdistribution Infectivity =
∑I x * Ro
x
∑I x * Ro

∑I x * Ro
× 100 (10.8)
ma1 ma2 man
The age- and gender-wise distribution breakup was estimated using the above time series
model equation (10.20). As per the model results, the total number of population considered
was 5,452, of which males were 3,666/5,452 = 67.24% and females were 1,786/5452 = 32.75%,
with a sex ratio of 1:0.5. The mean age of the male patients was 41.55 years with an SD of
0.22, and the mean age of females was 45.47 years with SD 0.89. The age group was catego-
rized based on the mean and SD of data series. Males were predominately more affected
than females. Children are the least affected population among the age groups: 0–9 years
(14, <1%) [odds < 1, CI 95% 0.21–0.36, p value = 0.663]; 10–19 years (19, 0.34%) [odds < 1,
CI 95% 0.12–0.38, p value = 0.744]; 20–29 years (108, 1.98%) [odds < 1, CI 95% 0.12–1.58, p
value = 0.368]; 30–39 years (261, 4.78%) [odds 2.085, CI 95% 3.55–5.58, p value = 0.001]; 40–49
years (583, 10.69%) [odds 2.68, CI 95% 8.67–13.55, p value = 0.0001]; 50–59 years (1,142, 20.94%)
[odds 10.74, CI 95%16.38–28.55, p value = 0.001]; 60–69 years (1,486, 27.25%) [odds 5.63, CI 95%
21.88–32.85, p value = 0.001]; and >70 years (1,839, 33.73%) [odds 6.88, CI 95% 30.28–36.89,
p value = 0.0001] (Table 10.2).
TABLE 10.2
Age-Wise Breakup of COVID-19 in India
Male Female Total
Age Number Percent (%) Number Percent (%) Number Percent (%)
0–9 years 08 0.22 06 0.33 14 0.25
10–19 years 14 0.38 05 0.28 19 0.34
20–29 years 71 1.94 37 2.07 108 1.98
30–39 years 179 4.88 82 4.59 261 4.78
40–49 years 403 10.99 180 10.07 583 10.69
50–59 years 740 20.19 402 22.50 1,142 20.94
60–69 years 974 26.57 512 28.66 1,486 27.25
>70 years 1,277 34.83 562 31.46 1,839 33.73
Total 3,666 100 1,786 100 5,452 100
10.4 Time Series Stochastic Model in the Prediction

of the Second Wave of COVID in India
COVID-19 is scourge and a deadly disease that led to an unprecedented pandemic cri-
sis. Soon after, the proportion of infected drastically increased rapidly. The future of the
pandemic’s progress was uncertain, and thus, predicting the projection of surge of sec-
ond wave is crucial to the planners of the health policy and epidemiologists. The main
objective of the present section is to explore fitted time series stochastic models for the
estimation of surge of different waves of COVID-19 pandemic. These newer techniques
will fulfill our urge of estimation and prediction of accurate figures and also outperform
the time series modeling of traditional way simulation. Further, forecasting of surge of
COVID-19 is harder and the primary concern is reducing the long-standing effect of noise
data sets. For more understanding of the factors that contribute to the present scenario,
model accuracy constraints are very easily demonstrated and the uncertainties in the esti-
mation of credibility intervals of missing of substantial number of cases are reduced. So,
our fitted model is more plausible and provide full-blown information to the researchers
(Figures 10.1 and 10.2).
10.5 Model Formulation—Age-Specific Time Series

Let X1, X2…Xn be the random state time series variables of COVID series and Y1, Y2…
Yn be the dependent variables of time-varying infection. The case fatality rate (CFR) of
COVID-19 pandemic is
Yt= 0,1,2 3, n months = X t + X t−1 − 2 X t−1+ n + ε ij (10.9)
Yˆt= 0,1,2 3, n months = X

t + Xˆ t−1 − 2 Xˆ t−1+ n + εˆ ij (10.10)
FIGURE 10.1
Trend of age-specific incidence of COVID-19 in India.
FIGURE 10.2
Reproduction number and transmission mechanism.
where Yt = COVID-19 data series of infection rate varying with time “s” (t = 0, 1, 2, 3,
months, etc.) (Figures 10.3 and 10.4).
Minimize the error by using least squares analysis.
∑ (Y − ε ) t + Xˆ t−1 − 2 Xˆ t−1+ n + εˆ ij
2
t ij =X (10.11)
FIGURE 10.3
Mechanism of reproduction number changed new infection.
∑ (Y − ε ) t X ′ + Xˆ t−1 X ′′ − 2 Xˆ t−1+ n X ′ + εˆ ij Minimizetheerrors

2
t ij =X (10.12)
where
X ′ = θ , the unobserved components estimated based on real data series
X ′′ = θ ′, the observed components estimated based on substitutional method
(arbitrary assumptions)
Xt = the real COVID time series at time t
X t−1 = the lag period or month
X t−1+ n = the difference of lag period at nth time interval
ε ij = the errors associated with ith period (t = 0, 1, 2, nth time) at jth region.
10.5.1 Model Output
The age-wise distribution breakup was estimated by using the above time series model
equation (10.20). As per the model results, it is revealed that a total of 1,373 cases were
considered for the study intervention. The age-wise distribution was estimated from
the above model constructed. The age group 0–5 years had 37 cases (2.69%); 6–9 years 50
(3.64%); 10–19 years 177 (12.89%); 20–29 years 340 (24.76%); 30–39 years 329 (23.96%); 40–49
FIGURE 10.4
Age-wise prevalence breakup of males and females in India.
years 177 (12.89%); 50–59 years 119 (8.64%); and > 60 years 144 (1.49%). All age groups were
shown to be statistically significant (odds ratio >1.0, p < 0.001), and the death rate was also
estimated using the same constructed model. The death rate or CFR was more in the age
group of >60 years (>25%) because the patients in this age group suffered from clinical
underlying conditions or one or more comorbidities (Table 10.3).
The symptoms were correlated in the first and second wave of COVID-19. The results
showed that symptoms of the first and second wave significantly differ with different age
groups. In case of the first wave, percent prevalence of loss of taste and smell was 85%;
shortness of breath 19% [odds 3.55, CI 95% 10.55–21.22, P = 0.001]; congestion 5% [odds
0.55, CI 95% 2.15–6.66, P = 0.128]; body ache 76% [odds 4.88, CI 95% 65–85, P = 0.001]; head-
ache 65% [odds 2.88, CI 95% 45–75, P = 0.001]; fever/chills/shivers 88% [odds 9.11, CI 95%
81–97, P = 0.001]; dry cough 68% [odds 3.66, CI 95% 58–71, P = 0.001]; and fatigue 38% [odds
2.88, CI 95% 31–45, P = 0.001]. A similar approach was used for the estimation of signifi-
cance of symptoms in the second wave. The symptoms showed drastic changes compared
TABLE 10.3
Observational Case Study of Age-Specific Infection in One of the Indian States (Karnataka)
Age-Wise Distribution Number % Odds Ratio P-value Death Rate in India
0–5 years 37 2.69 3.4 ≤0.001 0.0
6–9 years 50 3.64 5.6 ≤0.001 0.0
10–19 years 177 12.89 7.89 ≤0.001 0.12%
20–29 years 340 24.76 10.44 ≤0.001 0.20%
30–39 years 329 23.96 4.58 ≤0.001 0.20%
40–49 years 177 12.89 11.97 ≤0.001 0.4%
50–59 years 119 8.64 12.23 ≤0.001 1.3%
>60 years 144 1.49 8.67 ≤0.001 25%
to the surge of the first wave: tiredness 80% [odds 6.88, CI 95% 74–85, P = 0.001]; fatigue
75% [odds 3.88, CI 95% 68–88, P = 0.001]; lethargy 15% [odds 2.41, CI 95%12–18, P = 0.001];
body ache 45% [odds 4.68, CI 95% 41–55, P = 0.001]; diarrhea 22% [odds 2.33, CI 95% 18–26,
P = 0.001]; vomiting 12% [odds 1.25, CI 95% 10–17, P = 0.001]; stomach pain 25% [odds 3.01,
CI 95% 20–28, P = 0.001]; and cold and fever absent 10%–15% [odds 2.89, CI 95% 9.88–19.18,
P = 0.001] (see Table 10.4).
The CFR was estimated in both the first and second wave using pooled data sets of the
USA and India. The results showed that in the age group from <40 years to 60–69 years, the
CFR was <5% in the USA. In case of India, the CFR was <5% only in the age group <40 years.
The maximum CFR was documented in the age group 70–79 years (20.22%) [odds 4.77, CI
95% 18–25, P = 0.001], followed by the age group 60–69 years (16.80%) [odds 11.241, CI 95%
10–21.18, P = 0.001] (Table 10.5).
The percentage need for oxygen in the first and second waves is presented in Table 10.6.
Results showed that the percent of patients who needed oxygen in the age group <30 years
was 31% [odds 15.88, CI 95% 21–38, P = 0.001] as compared to elderly population—30–40
years (21%) [odds 10.85, CI 95% 17–26, P = 0.001]. In case of geriatric population with under-
lying clinical conditions, the oxygen requirement is more >45% [odds 21.14, CI 95% 38–55,
P = 0.001]. The research findings were significantly correlated with respect to age- and
gender-wise distributions (Figures 10.5 and 10.6).
Structural time series model equations (10.9–10.12) were applied for forecasting and
interpolation of COVID-19 transmission rate. As per the model, the positivity rate of Assam
was the lowest and the maximum positivity was attained in Goa (40.80%), Delhi (31.70%),
TABLE 10.4
Symptoms of the First and Second Wave of COVID
First Wave Second Wave
Loss of taste and smell (85%) Tiredness (80%)
Shortness of breath (19%) Fatigue (75%)
Congestion (5%) Lethargy (15%)
Body ache (76%) Body ache (45%)
Headache (65%) Diarrhea (22%)
Fever/chills/shivers (88%) Vomiting (12%)
Dry cough (68%) Stomach pain (25%)
Fatigue (38%) Cold and fever absent (10%–15%)
TABLE 10.5
Case Fatality Rates (COVID Induced) in the USA and India
USA India
Age (years) CFR (%) CFR (%)
Under 40 0.2 1.20
40–49 0.40 8.20
50–59 1.3 10.80
60–69 3.6 16.80
70–79 8.0 20.22
>80 14.80 9.86
TABLE 10.6
Percentage Need for Oxygen in First and Second Waves
Infected First Wave Second Wave Odds Ratio P-value
<30 years 31% 32% 12.08 <0.001
30–40 years 21% 21% 8.76 <0.001
Seriousness of infection
Shortness of breath 41.70% 47.50% 15.44 <0.001
Needing oxygen 41.10% 54.50% 21.25 <0.001
MOHFW, GOI, report, April 2021. https://www.mohfw.gov.in/
1277 34.83% 562

>70 years 31.46%
974 26.57% 512
60 -69 years 28.66%
740 20.19% 402
50 -59 years 22.50%
403 10.99% 180
40 -49 years 10.07%
179 4.88% 82
30-39 years 4.59%
71 1.94% 37
20-29 years 2.07%
14 0.38% 5
10-19 years 0.28%
8 0.22% 6
0-9 years 0.33%
0% 20% 40% 60% 80% 100%
FIGURE 10.5
Case fatality rat of different age group.
West Bengal (29.60%), Chhattisgarh (21%), Haryana (26.0%), Kerala (23.80%), Maharashtra
(22.7%), Madhya Pradesh (21.80%), Karnataka (21%), etc. A positivity of <10% was recorded
in Telangana (8.5%), Gujarat (8.5%), and Jammu and Kashmir (7.30%). Overall, the positiv-
ity rate in India was 21.40% as of May 7, 2021, and it increased to >40% in the period from
the end of May to June 2021. There is no seasonal variation in Indian states, except in
Uttarakhand (the seasonal effect was 1.65; see Table 10.7).
10
9
8
7
6
5
%
4
3
2 Death rate
1
0
FIGURE 10.6
Case fatality rate (CFR) comparison of COVID-19 pandemic in top countries.
TABLE 10.7
COVID-19 Second Wave Positivity Rate in Indian States
Structural Time Series Model—Interpolation
States Percent Positivity (as of May 4, 2021) Level Slope Seasonal Stand. Residuals
Goa 40.8 40.80 0.00 0.00 0.00
Delhi 31.7 32.81 −1.11 −1.11 −1.98
West Bengal 29.6 30.73 −1.15 −1.13 −0.53
Chhattisgarh 27.7 28.84 −1.18 −1.14 −0.41
Haryana 26 27.14 −1.20 −1.14 −0.28
Kerala 23.8 24.97 −1.25 −1.17 −0.53
Maharashtra 22.7 18.95 −1.17 3.75 −3.00
Madhya Pradesh 21.8 22.23 −0.76 −0.43 2.03
India 21.4 21.94 −0.73 −0.54 0.25
Karnataka 21 21.54 −0.70 −0.54 0.17
Chandigarh 21 21.51 −0.66 −0.51 0.36
Rajasthan 21 21.43 −0.61 −0.43 0.31
Himachal Pradesh 20.7 18.64 −0.73 2.06 −1.23
Andhra Pradesh 19 19.27 −0.61 −0.27 0.66
Puducherry 18 18.45 −0.63 −0.45 −0.11
Odisha 17.3 17.75 −0.63 −0.45 −0.04
Jharkhand 14.8 15.36 −0.78 −0.56 −0.93
Uttar Pradesh 14.6 14.79 −0.76 −0.19 0.11
Uttarakhand 14.4 12.75 −0.86 1.65 −0.70
Bihar 13.6 13.71 −0.70 −0.11 0.91
Tamil Nadu 13 13.40 −0.66 −0.40 0.20
Punjab 12.2 12.51 −0.68 −0.31 −0.12
Telangana 8.5 9.20 −0.91 −0.70 −1.38
Gujarat 8.5 8.50 −0.90 0.00 0.11
Jammu & Kashmir 7.3 6.08 −1.03 1.22 −0.82
Assam 5 5.12 −1.02 −0.12 0.03
Data source: Times of India news paper, dated May 7, 2021.
Table 10.8 depicts that the projection of surge of COVID-19 in the Indian context. Results
showed that the cohort of various months of different waves was predicted by using real data
sets collected from MoHFW, Government of India. As per the model output, the cohorts of
June 2021 (3.78%), July 2021 (3.07%), and August 2021 (<1.0%) had a decreased positivity rate
and a negative movement was seen in October and November 2021. No seasonal variation
was seen in the six-month cohort of predicted COVID-19 surge. Slope levels were positively
associated; epidemiological deviation was taking place in summer season because slope
levels positively moved with infectivity. Precautionary and preventive measures would be
implemented to control the surge of projected waves of COVID-19 (Figures 10.7–10.10).
Figure 10.11 shows the causal relation between the variables. Typically, the parameters
were expressed unknown. Due to the varied time series data sets, the direction of the
edges in the graph would be varied and thus causal effects can be identified from the
TABLE 10.8
Probable Month of COVID-19 Second Wave End in Indian States (Top Prevalence)
Structural Time Series Model—Extrapolation
Months (2021) Percent Positivity Decline Level Seasonal
June 3.78 4.14 −0.35
July 3.07 2.83 0.25
August 0.88 1.52 −0.64
September 0.59 0.21 0.38
October −0.30 −1.10 −0.80
November −2.86 −2.41 −0.44
FIGURE 10.7
Recovered and death rate of COVID-19 pandemic in top countries.
FIGURE 10.8
Forecasted projection points of observed and seasonal components.
FIGURE 10.9
Graphical representations of projection points of observed and seasonal components.
FIGURE 10.10
Standardized residuals of observed and seasonal components.
FIGURE 10.11
Seasonal decomposition by LOESS model.
individual series of surge of COVID data series. Many graphical representations were
expressed in different ways on multiplicative and additive factors for identifying the varia-
tion effects, which may lead to wrong conclusions and identifications of many causal effect
relations. In this research gap, we used the Granger causality measure components graph
to study the association between variables at varied time intervals; therefore, we cannot
distinguish between the direct causal effects and the association that is due to unmea-
sured confounders of COVID-19 data series. Based on Figure 10.1 we correlate the effects
of a confounder on two variables lagged in time. The resulting association between lagged
variables falsely leads to a direct edge between the corresponding vertices in the causal-
ity relation graph. Time is unforgettable COVID-19 deleteriously affects the population in
different seasons, and virus decay will start after 18–25 months of induction. However, in
certain situations, the causal properties can vary with management, policy-making deci-
sions, and prevention strategies (Tables 10.9).
From a statistical point of view, the product moment correlation coefficient is a simple
method to interpret the normalized version of a cross-correlation. Here, when two time
series data sets are cross-correlated, a measure of temporal similarity is achieved. In case
of COVID, we considered infectivity and CFR. Both parameters are very important for us
to correlate the relative differences between the factors at varied time intervals. However,
when the infectivity increases, the CFR drastically increases and vice versa. But due to
some epidemiological deviations and climatic variations, these factors would be reverted.
In this longevity of research gap, we correlate the temporal changes between infectivity
and CFR and also explore intuitiveness. As shown in Figure 10.12, no temporal variation
was seen in both factors. CFR will steadily maintain the same trend after a lag period of 20
months of COVID-19 pandemic crisis (Table 10.10).
We computed the ACF for a given time series data sets of COVID-19. The method was
very useful to know the random effects and the degree of relationship between the lag
period (the ACF to extract the successive observations is very small or massive), or we
have to find the highest correlation between the infectivity and CFR. In spite of explor-
ing the effects of lag period on data series, we diagnose the temporal relation between
various data points using Durbin–Watson statistic, Q–statistic, and the Breusch–Godfrey
LM test for its presence in the residuals of the predictive models. These are used for the
extrapolation of mean relation between lag periods. As per the model construction, after
TABLE 10.9
Variance Reduction Matrices of Structural Stochastic Model
Variance Reduction Matrix
V(Y[t],d = 0, D = 0) 66.62 Range 35.8 Trim variance 33.03

V(Y[t], d = 1, D = 0) 3.43 Range 9.1 Trim variance 0.56
V(Y[t], d = 2, D = 1) 6.69 Range 10 Trim variance 2.52
V(Y[t], d = 0, D = 2) 32 Range 8 Trim variance NA
V(Y[t], d = 1, D = 2) NA Range 0 Trim variance NA
V(Y[t], d = 2, D = 2) NA Range Inf Trim variance NA
V(Y[t], d = 3, D = 2) NA Range Inf Trim variance NA
FIGURE 10.12
Granger Causality—graphical representation (d = 0,1; D = 0,1).
TABLE 10.10
Granger Causality Test: Y = f(X)
Model Res. df Diff. df F P-value
Granger Causality Test: Y = f(X)
Complete model 356
Reduced model 357 −1 17.91 2.94
Granger Causality Test: X = f(Y)
Complete model 356
30–35 months of lag period of infection, CFR negatively correlated. No death rate would
be recorded in the given time period (Figures 10.13 and 10.14). The Durbin–Watson was
more than the reference range.
The exponential structural smoothing model will provide a video framework for fore-
casting massive data sets. These techniques are extremely reliable and have more than
adequate track record in forecast accuracy with trend, seasonal, and cyclic variations of
time series data. The exponential model is described in terms of a state space modeling
framework that provides a prediction interval and procedures for model selection and
is well suited for large-scale implementation. It is a flexible approach to weighting past
historical data sets for smoothing and extrapolation and interpolation purposes. The pres-
ent section describes how to construct structural stochastic models and the extraction of
constant terms using massive data with varied time intervals and lag periods.
FIGURE 10.13
Cross-correlation function time series predictive structural stochastic model.
FIGURE 10.14
Autocorrelation function (ACF) of predictive structural stochastic model.
10.6 Model 1
We consider Y1,Y2…Yn as the random series of data points with time “s”. The estimation of
smoothing term without regression is
Yt+1 = C1 X 1 + C2 X 2 …Ck X t−1+ 2 (10.13)
Yt+ 2 = C1 X 1 + C2 X 2 …Ck X t− 2+ 3 (10.14)
Yt+ n = C1 X 1 + C2 X 2 …Ck X t− n+ i (10.15)
∆Yt = Ck
C2 =
1
T ∑( ∆Y )
t=1
t (10.16)
C1 =
1
T ∑ (Y − C t )
t=1
t 2 (10.17)
Yˆt+1 = C 2 (T + 1) (Extrapolation is fast, regression free statistics)

1 + C
Model 1 assumes that y changes by a constant value C2 in each period. By contrast, the
exponential growth model assumed “y” changes by a constant value of data points.
Yt = e c1 + c2t (10.18)
dy / dt
= C2 (10.19)
yt
1
Yˆt+1 = ( yt + yt−1 + yt− 3 + yt− 4 … yt− n+ i ) (10.20)
Y
From the model output, Figures 10.15 and 10.16 show that after a three-year lag period (from
inception), infectivity would show a declining trend. No temporal variation was seen in
infectivity and CFR. The prediction errors are ignorable, and reproducibility is a greater
epoch for the extrapolation and interpolation of COVID massive time series data sets.
10.7 Discussion
The present study addresses the transmission mechanism of age-specific incidence of
COVID-19 at global platform. We extrapolated the model by using real data sets of SARS-
Cov-19 in association with age- and gender-specific contract rates in a COVID-19 time
FIGURE 10.15
Autocorrelation function (ACF) of transformed adjusted data sets of “Months.”
FIGURE 10.16
Extrapolation fit of exponential smoothing.
series structural stochastic and epidemiological model (Albi et al., 2020; Chen et al., 2019,
2020). The model permits the exploration of the effects of changes in mitigation measures
on the gender- and age-matched frequency. Our present model had three scenarios which
assumed ongoing distancing measures versus easing of contact restrictions in working
ages, and among adolescents and young adults. Our forecasting figures will provide accu-
rate projection points and estimated surge of COVID-19 in different geographical regions.
The model construction is very easy, and the data sets are pooled for the prediction of
forecasted figures at a reasonable time period without loss of information (Backer et al.,
2020; Boehmer et al., 2020; Busenberg et al., 1988; Doerre and Doblhammer, 2020). With
an insight into model building, we focused on practical standpoints of dynamic behavior
and the process of the spreading of COVID-19 while incorporating specific epidemiologi-
cal information on the virus and disease. The main merit of the model methodological
framework is that a considerable amount of all information was substituted with rela-
tively simple extrapolation by using the real number of disease pandemic reproduction
number R0 (SARS-Cov-19) (Dallavilla et al., 2020; Deng et al., 2020; Dos et al., 2018; Davies
et al., 2020; Deforche, 2020). However, the fitted model can be used to extend the uncer-
tainty, as described above. In the interest of model feasibility we extracted the relativ-
ity of factor from the disease reproduction number to know the behavioral mechanism
and epidemiological process to a greater extent and for reliable accuracy. Simulation of
massive data series was used to approximate the state and transition points of surge of
COVID from the above model. The model relies on the assumption that clinical profile
and epidemiological and biological traits were included in describing various patterns
of disease transmission mechanism (Dudas et al., 2014; Del Valle et al., 2013; Dudel et al.,
2020; Franceschetti et al., 2008; Fang et al., 2020; Forster et al., 2020; Faria et al., 2016). The
model mathematical formulations describing the independence of disease progression
considered all parameters. We observed that the individual projection points will provide
good information to the researchers for taking clinical decisions and also latent projec-
tion points for the estimation of posterior outbreak at different sites or national level. The
model makes a clear framework, which is particularly attractive for forecasting and inves-
tigating hypothetical scenarios. However, the model has demerits, i.e., lack of memory
for averaging rationale which treats population groups homogeneously and the average
number of contacts in each group, which is a determining parameter (Guan et al., 2020;
Gire et al., 2014; Greenhalgh et al., 1987; He et al., 2020; Jahangiri et al., 2020). This model
supports the idea that symptoms occur in a predictable order, but future work is needed
to improve the aspects of the stochastic convergent model that determined the results. The
present findings of the model will highly support the epidemiologists to recommend vari-
ous measures for the control surge of COVID-19 with age-specific approach. In contrast
to model simulation, random or systematic errors were not precluded and not driven by
the skewness. The fundamental mechanism of the present model will take massive data
points for the estimation of accurate forecasting figures (Hoffmann et al., 2020; Hoenen
et al., 2016; Hethcote, 2000). Considering the rapidly changing pandemic, it is important to
note that the proposed model can account for time-varying input parameters. This is use-
ful, as not only the number of deaths and infected cases changes on a daily basis, but also
we may calculate the treated and untreated projections in long-term intervals, which can
also accumulate analytical insights. Another strongest point is that the present model can
estimate COVID-19 infections in a simple and fast manner in various settings of rich and
poor data sets. It can be the only option in situations in which the detailed data needed for
precise estimation are unavailable and population representatives are at the community
level (Iannelli and Manfredi et al., 2007; Inaba, 1990; Jiang et al., 2020; Kulu and Dorey, 2020;
FIGURE 10.17
Interpolation fit of exponential smoothing.
Khot and Nadkar, 2020; Khan and Atangana, 2020; Liu et al., 2015; Lu et al., 2020; Monod
et al., 2021; Manfredi and Williams, 2004; Nishiura et al., 2020; Quick et al., 2016; Singh
and Adhikari, 2020). The model can be implemented broadly and provide useful informa-
tion about the magnitudinal differences of unknown parameters rediscover to quantify
the drastic deviations for the estimation of corresponding national estimates calculated
by epidemiologists and data scientists (Sobotka et al., 2020; Sahin et al., 2020; Tang et al.,
2020; Van de Kassteele et al., 2017; Wu and McGoogan, 2020; Wu et al., 2020; Yang, 2020;
Zhao et al., 2020a,b). The model outcomes can be used in decision making and as an input
to more advanced models. Moreover, information about the key input parameters of our
approach of estimation of CFR improves accurate infection estimates at population level
(Figure 10.17).
10.8 Conclusions
This chapter concludes that the estimation of different waves of the surge of COVID-19 is a
very difficult task to determine using the clinical and epidemiological settings in a single
point of time. However, the models are computationally intensive and accurately provide
useful information about prevalence trends in different age groups in various regions,
such as low, medium, and high prevalence (based on the infectivity rate).
References
Albi G., Pareschi L., Zanella M. Control with uncertain data of socially structured compartmental
epidemic models. medRxiv 2020. doi: 10.1101/2020.04.27.20081885.
Backer J.A., Klinkenberg D., Wallinga J. Incubation period of 2019 novel coronavirus (2019-nCoV)
infections among travellers from Wuhan, China, 20–28 January 2020. Euro Surveill 2020; 25:
2000062.
Boehmer T.K., DeVies J., Caruso E., et al. Changing age distribution of the Covid-19 Pandemic United
States, May–August 2020. Morb Mortal Wkly Rep 2020; 69: 1404–1409.
Busenberg S., Cooke K., Iannelli M. Endemic thresholds and stability in a class of age-structured
epidemics. SIAM J Appl Math 1988; 48: 1379–1395.
Chen S., Yang D., Liu R., Zhao J., Yang K., Chen T. Estimating the transmissibility of hand, foot, and
mouth disease by a dynamic model. Public Health 2019; 174: 42–8.
Chen T., Rui J., Wang Q., Zhao Z., Cui J.-A., Yin L. A Mathematical model for simulating the phase-
based transmissibility of a novel Coronavirus. Infect Dis Poverty 2020; 9: 24.
Dallavilla T., Bertelli M., Morresi A., Bushati V., Stuppia L., Beccari T., et al. Bioinformatic analy-
sis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses. Eur Rev Med
Pharmacol Sci 2020; 24: 4558–4564. doi: 10.26355/eurrev_202004_21041.
Davies N.G., Klepac P., Liu Y., Prem K., Jit M., CMMID Covid-19 Working Group, Eggo R M. Age-
dependent effects in the transmission and control of Covid-19 epidemics, Nature Med 2020; 26:
1205–1211. doi: 10.1038/s41591-020-0962-9.
Deforche K. An age-structured epidemiological model of the Belgian Covid-19 epidemic. medRxiv
2020; doi: 10.1101/2020.04.23.20077115.
Del Valle S.Y., Hyman J.M. and Chitnis N. Mathematical models of contact patterns between age
groups for predicting the spread of infectious diseases. Math Biosci Eng 2013; 10: 1475–1497. doi:
10.3934/mbe.2013.10.1475.
Deng X., Gu W., Federman S., Du Plessis L., Pybus O., Faria N., et al. A genomic survey of SARS-
CoV-2 reveals multiple Introductions into Northern California without a predominant lineage.
medRxiv 2020. doi: 10.1101/2020.03.27.20044925.
Doerre A., Doblhammer G. Age- and sex-specific modelling of the Covid-19 epidemic. medRxiv 2020.
doi: 10.1101/2020.10.06.20207951.
Dos S.R.C., Koopmans M.P., Haringhuizen G.B. Threats to timely sharing of pathogen sequence data.
Science 2018; 362: 404–406. doi: 10.1126/science.aau529.
Dudas G., Rambaut A. Phylogenetic analysis of guinea 2014 Ebolavirus outbreak. PLoS Curr 2014;
6: 238–139.
Dudel C., Riffe T., Acosta E., van Raalte A.A., Strozza C. and Myrskyl M. Monitoring trends and
differences in Covid-19 case fatality rates using decomposition methods: Contributions of age
structure and age-specific fatality. medRxiv 2020; doi: 10.1101/2020.03.31.20048397.
Fang B., Liu L., Yu X., Li X., Ye G., Xu J., et al. Genome-wide data inferring the evolution and pop-
ulation demography of the novel pneumonia coronavirus (SARS-CoV-2). BioRxiv 2020. doi:
10.1101/2020.03.04.976662.
Faria N.R., da Silva Azevedo R.S., Kraemer M.U.G., Souza R., Cunha M.S., Hill S.C. et al. Zika virus
in the Americas: Early epidemiological and genetic findings. J Sci 2016; 352: 345–9. doi: 10.1126/
science.aaf5036.
Forster P., Forster L., Renfrew C., Forster M. Phylogenetic network analysis of SARS-CoV-2 genomes.
Proc Natl Acad Sci USA 2020; 117: 9241–9243. doi: 10.1073/pnas.2004999117.
Franceschetti A., Pugliese A. Threshold behaviour of a SIR epidemic model with age structure and
immigration. J Math Biol 2008; 57(1): 1–27.
Gire S.K., Goba A., Andersen K.G., Sealfon R.S.G., Park D.J., Kanneh L. et al. Genomic surveillance
elucidates Ebola virus origin and transmission during the 2014 outbreak. J Sci 2014; 345: 1369–
1372. doi: 10.1126/science.1259657.
Greenhalgh D. Analytical results on the stability of age-structured recurrent epidemic models. IMA J
Math Appl Med Biol 1987; 4: 109–144.
Guan W., Ni Z., Hu Y., Liang W., Ou C., He J., et al. Clinical characteristics of coronavirus disease 2019
in China. New Engl J Med 2020; 382: 1708–1720.
He D., Zhao S., Lin Q., Zhuang Z., Cao P., Wang M.H., et al. The relative transmissibility of asymp-
tomatic Covid-19 infections among close contacts. Int J Infect Dis 2020; 94: 145–147.
Hethcote H.W. The mathematics of infectious diseases. SIAM Rev 2000; 42(4): 599–653.
Hoenen T., Groseth A., Rosenke K., Fischer R.J., Hoenen A., Judson S.D. et al. Nanopore sequencing
as a rapidly deployable Ebola outbreak tool. Emerg Infect Dis 2016; 22: 331–334. doi: 10.3201/
eid2202.151796.
Hoffmann M., Kleine-Weber H., Schroeder S., Kruger N., Herrler T., Erichsen S., et al. SARS-CoV-2
cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhib-
itor. Cell 2020; 181: 271–280. doi: 10.1016/j.cell.2020.02.052.
Iannelli M., Manfredi P. Demographic change and immigration in age-structured epidemic models.
Math Populat Stud 2007; 14: 169–191.
Inaba H. Threshold and stability results for an age-structured epidemic model. J Math Biol 1990; 28:
411–434.
Jahangiri M., Jahangiri M., Najafgholipour M. The sensitivity and specificity analyses of ambient
temperature and population size on the transmission rate of the novel coronavirus (Covid-19)
in different provinces of Iran. Sci Total Environ 2020; 728: 138872.
Jiang Y., Wei X., Guan J., Qin S., Wang Z., Lu H., et al. Covid-19 pneumonia: CD8(+) T and NK cells
are decreased in number but compensatory increased in cytotoxic potential. Clin Immunol 2020;
218: 108516. doi: 10.1016/j.clim.2020.108516.
Khan M.A., Atangana A. Modeling the dynamics of novel Coronavirus (2019-nCov) with fractional
derivative. Alex Eng J 2020; 3: 1–11.
Khot W.Y., Nadkar N.Y. The 2019 novel Coronavirus outbreak: A global threat. J Assoc Phys India
2020; 68(3): 67–71.
Kulu H., Dorey P. The contribution of age structure to the number of deaths from Covid19 in the UK
by geographical units. medRxiv 2020; doi: 10.1101/2020.04.16.20067991.
Liu R., Leung R.K., Chen T., Zhang X., Chen F., Chen S., et al. The effectiveness of age-specific isola-
tion policies on epidemics of influenza a (H1N1) in a large city in central South China. PLoS
One 2015; 10: 132588.
Lu R., Zhao X., Li J., Niu P., Yang B., Wu H., et al. Genomic characterisation and epidemiology of
2019 novel coronavirus: Implications for virus origins and receptor binding. Lancet 2020; 395:
565–574. doi: 10.1016/s0140-6736(20)30251.
Manfredi P., Williams J. Realistic population dynamics in epidemiological models: The impact of
population decline on the dynamics of childhood infectious diseases. Measles as an example.
Math Biosci 2004; 192: 153–175.
Monod M., Blenkinsop A., et al. Age groups that sustain resurging Covid-19 epidemics in the United
States. Science 2021; 371(6536): 8372.
Nishiura H., Kobayashi T., Miyama T., Suzuki A., Jung S.M., Hayashi K., et al. Estimation of the
asymptomatic ratio of novel coronavirus infections (Covid-19). Int J Infect Dis 2020; 94: 154–155.
Quick J., Loman N.J., Duraffour S., Simpson J.T., Severi E., Cowley L., et al. Real-time, portable
genome sequencing for Ebola surveillance. Nature 2016; 530: 228–232 doi: 10.1038/nature16996.
Sahin A.R., Erdogan A., Agaoglu P.M., et al. 2019 novel coronavirus (Covid-19) outbreak: A review of
the current literature. EJMO 2020; 4(1): 1–7.
Singh R., Adhikari R. Age-structured impact of social distancing on the Covid-19 epidemic in India.
medRxiv 2020; 2003: 12055.
Sobotka T., Brzozowska Z., Muttarak R., Zeman K., di Lego V. Age gender and Covid19 infections.
medRxiv 2020; doi: 10.1101/2020.05.24.20111765.
Tang B., Bragazzi N.L., Li Q., et al. An updated estimation of the risk of transmission of the novel
Coronavirus (2019-nCov). Infect Dis Model 2020; 5: 248–255.
Van de Kassteele J., van Eijkeren J., Wallinga J. Efficient estimation of age-specific social contact rates
between men and women. Ann Appl Stat 2017; 11(1): 320–339. doi: 10.1214/16-AOAS1006.
spread of the 2019-nCoV outbreak originating in Wuhan, China: A modelling study. The Lancet
2020; 395(10225): 689–697.
Wu Z., McGoogan J.M. Characteristics of and important lessons from the coronavirus disease 2019
(Covid-19) outbreak in China, summary of a report of 72 314 cases from the Chinese center for
disease control and prevention, JAMA 2020; 323(13): 1239–1242.
Yang C. A mathematical model for the novel coronavirus epidemic in Wuhan, China. Math Biosci Eng
2020; 17(3): 2708–2724.
Zhao S., Lin Q., Ran J., Musa S.S., Yang G., Wang W., et al. Preliminary estimation of the basic repro-
duction number of novel coronavirus (2019-nCoV) in China, from 2019 to 2020: A data-driven
analysis in the early phase of the outbreak. Int J Infect Dis 2020a; 92: 214–217.
Zhao Z., Zhu Z.Y., Xu J.W., et al. A mathematical model for estimating the age-specific transmissibil-
ity of a novel coronavirus. Infect Dis Poverty 2020b; 9: 24–25.
11
National Health Policies and Their
Perspectives on the Approach to Control
COVID-19 and Other Infectious Diseases
11.1 Introduction
A health policy generally describes the fundamental principles regarding which health
providers are expected to make valuable decisions (Basavarajaiah and Narasimha Murthy,
2020). A health policy provides a broad framework of decisions for guiding health activities
that are useful to its community in improving their health, regarding the gap between the
health status of haves and have-nots, and ultimately contributes to the quality of life (QOL)
(Agurto et al., 2006; Agyepong and Adjer, 2007; Patton et al., 2016; Coiera et al., 2006; North,
1990). NHP stresses the need for primary health care with a special emphasis on preven-
tion, promotion, and rehabilitation. From a broad perspective, why is health policy cru-
cial for good governance and management of population in pandemic crisis? Rather than
policy implications, health policy is a set of addressable issues framed under constitutional
privilege. We have drafted a health policy in an explicit way and is equally treated as a
narrative law encompassed with directive principles and recommendations for the imple-
mentation of an exclusive form without overlaps (Remme et al., 2010; Yazdani and Wells,
2018). However, with an inclusive approach, the policy will reflect the inter-sectoral linkage
that facilitates the wider scope for expert vetting and provide suggestions to draft people-
oriented disease prevention programs that ensure feasibility and flexibility. At the outset,
we express that whether it is the health policy or healthcare policy that alters policy amend-
ment with varied time in the long run. The purpose of the policy draft is clearly an explicit
statement of a commitment by the government, and such a policy document should be ethi-
cally justifiable, epidemiologically sound, socially or culturally acceptable, and economi-
cally rational (Waddington, 1990). In spite of the policy implications, we consider the social
and cultural dimensions of health policy including political mobility, which is more often
concerned with the influence of power groups such as the ruling political party, opposition,
and trade union. The traditional methodology for health policy development is drafted
by the constitutional privilege of an expert committee, development of a draft policy by
reviewing existing documents and health statistics appraisal, identification of issues, defi-
nitions of the issues, framing solutions or recommendations, and modifications through a
series of discussion and meetings—multiple sittings of the committee and tabletop exer-
cises. This process is usually followed by vetting the initial draft by another short panel
of experts, putting the whole document in the public domain for opinion generation, and
finally endorsed by the legislature or House of Commons (Thaddeus, 1994). Article 39(E)
describes the basic method of policy analysis and methodology without reference to basic
DOI: 10.1201/9781003204794-11 299
scientific disciplines such as epidemiology, sociology, or economics (Basavarajaiah and

Narasimha Murthy, 2020). This chapter has attempted to explore the scope for the incor-
poration of scientific methodology. This process of health policy development is available
in many kinds of literature, and in this regard, we have reviewed the health policy guide-
lines (Basavarajaiah and Narasimha Murthy, 2020). The whole exercise is undertaken with
the purpose of reviewing the guidelines for new policy development of COVID and other
infectious diseases in the Indian context. This chapter attempts to address the key issues
of national policy implication, and we are explaining the importance of methodological
aspects in correlation with the policy development process. The policy development pro-
cess of different states passes through various stages at many points, and also the policy
formation cycle is repeated several times. The comprehensive final health policy in differ-
ent states were projected and published in various journals and periodicals for dissemina-
tion purposes. (Chen et al., 2020).
11.2 What is Health Policy?

An objective of National Health Policy is to create the conditions that ensure good health for
the entire population. Health policy should not be synonymous with medical care policy,
which is only a variable under health policy (Collins, 2005). Various definitions and the dif-
ferences between these definitions are matters of discussion in the literature. Public policy is
defined as a course of the method of action selected usually by the government, from among
alternatives to guide and determine present and future decisions. Health policy is a subset
of public policy. Health policy refers to decisions, plans, and actions that are undertaken to
achieve specific healthcare goals within a society. An explicit health policy defines a vision
for the future, which in turn helps to establish targets and points of reference for the short-
and medium-term plans. It outlines priorities and the expected roles of different groups
and builds consensus and informs the public or citizens of India. Merriam-Webster’s online
dictionary defines policy as (i) “a definite course or method of action selected from among
alternatives and in light of given conditions to guide and determine present and future deci-
sions” and (ii) “a high-level overall plan embracing the general goals and acceptable proce-
dures especially of a governmental body.” It is a statement of decision regarding a goal in
health care and a plan for achieving that goal, for example, to prevent an epidemic of infec-
tious diseases at the national level (Carter and Shieh, 2015; Ciliska et al., 2005; Peters et al.,
2007). Methodological considerations are very important to develop a flawless or technically
sound explicit policy in terms of its epidemiology limitations, evidence base, socio-cultural
acceptance, and political sensitiveness (Edward et al., 2011; Faden et al., 2013; Fan et al., 2014).
However, basically epidemiological methods for health needs assessment (estimates such
as the prevalence of illness), social science methods, and community needs assessment and
rapid appraisal techniques are used for assessing health-related outcomes and quality of life.
11.3 Methodological Considerations
The methodology is important to develop a flawless or technically sound explicit policy
in terms of its epidemiology limitations, evidence base, socio-cultural acceptance, and
NHPs and Control of COVID-19 301
political sensitiveness. The methodological considerations area needs to review the overall
well-being and quality of life of an individual: Basically, we assess the policy by epidemio-
logical methods for framing of new guidelines related to various health domains. Another
well-versed method broadly used regarding epidemic diseases (assessment estimates such
as the prevalence of illness) is the social science method. Community needs assessment
and rapid appraisal techniques are used for assessing health-related outcomes and qual-
ity of life (QOL). Furthermore, an assessment of resources is carried out using a situation
analysis or gap analysis; usually, it is to be done as a sector-wise or region-wise assessment
just like the evaluation of fiscal or human resource or inventory, for areas of content, etc.
Other specific methods used in economics that are needed are prioritization and quanti-
tative techniques such as modeling. This approach or perspective can be analyzed at the
stakeholder level or national/state/micro- or macro-level or at domain or content level
(sartorial policies) or from the perspectives of groups such as minorities, especially disad-
vantaged groups. In other words, specific methodologies of social science, such as a case
study, comparisons of worst-case and best-case scenarios, network or path analysis, and
pictorial depictions such as network models, can be employed. Involvement of public in
the policy development process or ensuring pro-people nature is required as discussed by
Basavarajaiah and Narasimha Murthy (2020). A quantitative technique such as microsimu-
lation is important for impact evaluation (Guldenmund et al., 2000). Health policy as a part
of public policy and the six key characteristics of public policy are also applicable in this
regard. These are strategic, outcome-focused, joined-up, inclusive, flexible and innovative,
and robust nature of the policy (Hansen et al., 2008; Hadaya et al., 2020). Now, pandemic
crisis health policy is the key indicator in the present scenario. The context has changed
in four major ways. First, health priorities are changing. Although the COVID-19-affected
population is exploited economically and politically and the mortality that reached up to
>2.50% of the population has rapidly declined, there is a growing burden on account of
infectious diseases and pandemic crisis worldwide. The second important change is the
emergence of a robust healthcare industry, estimated to be growing at double digits. The
third change is the growing incidences of catastrophic expenditure due to healthcare costs,
which are presently estimated to be one of the major contributors to poverty. The fourth
change is that the rising economic growth enables enhanced fiscal capacity. Therefore,
a new health policy response to these contextual changes is required at the national as
well as global level. The primary aim of the National Health Policy is to inform, clarify,
strengthen, and prioritize the role of the government in shaping health systems in all its
dimensions—investments in health, organization of healthcare services, prevention of
pandemic diseases such as COVID-19, and also promotion of good health through impedi-
ment policy actions, access to many technologies, developing human resources, encourag-
ing medical pluralism, building a knowledge base, developing better financial protection
strategies, strengthening regulation, and health assurance of the nation. The NHP 2021
builds on the progress made since the last NHP in 2002 (Basavarajaiah and Narasimha
Murthy, 2020). The developments have been captured in the document “Backdrop to
National Health Policy especially COVID pandemic 2021” is situation-based drafting
(Ministry of Health and Family Welfare, Government of India). Communicable diseases
are clearly defined, health policy is a method in which outcomes and patterns of health
determinants are implemented, and the new interventions encourage healthy behaviors
for individuals or populations through program elements or strategies designed to pro-
duce behavior changes or improve health domains. However, health policy recognizes
the interrelationship between communicable and infectious disease control programs
and public health system strengthening. The Integrated Disease Surveillance Programme
(IDSP) will achieve an acceptable standard of good health of the population, ensuring that
the policy advocates the need for distinct responses and communicates full-blown infor-
mation that pertains to the pandemic and communicable disease priorities of their locality.
This could be through a network of well-equipped laboratories backed by tertiary care
centers and enhanced public health capacity to collect, analyze, and respond to the disease
outbreaks that altered the pandemic crisis.
11.3.1 Control of Infectious Disease COVID-19 Pandemic

COVID-19 is a deadly and more devastating disease that deeply penetrates the population
worldwide. The National Health Policy intervention is very important for the eradication
of the disease, which also urgently needs curative measures or initiatives steps concerning
every government healthcare authority at international platform. The reasons for imple-
menting the new health policy are shown in Figure 11.1.
It helps in the attainment of the highest possible level of health and well-being for all ages
through a preventive and primitive healthcare orientation in all developmental processes.
The policy provides access to good-quality healthcare services without anyone having to face
financial hardship as a consequence. However, this would be achieved through increasing
medical service access, improving quality, and lowering the cost of healthcare delivery. The
policy recognizes the pivotal importance of sustainable developmental goals (Figure 11.2).
The main goal of COVID-19 health policy intervention is to progressively achieve uni-
versal health coverage, reinforcing trust in the public healthcare system, and align the
growth of private healthcare sectors with public health goals.
11.3.2 Control of Tuberculosis by NHP

The policy acknowledges COVID-associated illnesses such as HIV and TB co-infection
and increased incidence of drug-resistant tuberculosis as key challenges in the control of
tuberculosis. The policy calls for more active case detection, with a greater involvement of
FIGURE 11.1
Flowchart of National health policy implication.
FIGURE 11.2
Key points of COVID-19 National Health Policy.
the private sector supplemented by preventive and primitive actions in the workplace and
in living conditions. We will be able to access free drugs, which would need to be comple-
mented by affirmative actions that can ensure that the treatment is carried out, dropouts
are reduced, and transmission of resistant strains is contained.
11.3.3 Control of HIV/AIDS
While the current emphasis on prevention continues, the policy recommends focused
interventions on the high-risk communities (MSM, transgender, FSW, etc.) and prioritized
geographies. There is a need for support, care, and treatment for people living with HIV/
AIDS through the inclusion of first-, second-, and third-line antiretroviral (ARV), Hep C
(HIV co infection), and other costly drugs into the essential medicine list.
11.3.4 Leprosy Elimination
To eliminate leprosy, the proportion of grade 2 cases among new cases becomes the mea-
sure of community awareness and health systems capacity, keeping in mind the global
goal of reduction of grade 2 disability to less than 1 per million by 2022. Accordingly, the
policy states that proactive measures were targeted toward the elimination of leprosy from
India by 2022.
11.3.5 Vector-Borne Disease Control

The policy recognizes the challenge of drug resistance in malaria, which should be dealt
with by changing treatment regimens with logistics support as appropriate. The New
National Programme for Prevention and Control of Japanese Encephalitis (JE)/Acute
Encephalitis Syndrome (AES) should be accelerated with a strong component of inter-sec-
toral collaborations. The policy recognizes the interrelationship between communicable
disease control programs and public health system strengthening. Every one of these pro-
grams requires a robust public health system as its core delivery strategy. At the same
time, these programs also lead to the strengthening of healthcare systems.
11.4 Rationality of Health Policy During Emergency

COVID-19 vaccine development and use depend on the data-driven assessment of benefits
and risks, first by regulatory bodies, and then more subjectively, millions of times over, by
individual physicians and patients. Some new vaccines have transformed public health for
the control of COVID-19 pandemic (Sputnik, Covaxin, Covishield, Pfizer, etc.), whereas oth-
ers have failed to work in high-risk populations (HIV-associated illness, cancer, malaria,
etc.) or were later found to have important unexpected adverse effects. The regulatory
review of numerous coronavirus disease 2019 (COVID-19) vaccine candidates occurred
under intense clinical, economic, and political pressure. In early August 2020, the US
President Donald Trump predicted that a vaccine was available before the Election Day.
Less than a week later, Russia claimed to have developed its own vaccine and was begin-
ning widespread administration without completion of the large-scale testing that Western
countries routinely require, leading to efficacy–risk questions for wider public attention. We
acknowledge the pressure the US Food and Drug Administration (FDA) must have faced on
this front. Its leadership stated that no vaccine will receive formal approval unless it met the
agency’s published standards. As with drugs, the efficacy and safety of a vaccine are not
binary. Each drug should have a gradient and subject to varying definitions over time
(Mandala et al., 2009). In its June 2020 guidance document, the FDA established its expecta-
tion that an approved vaccine reduced the occurrence or severity of disease in at least 50%
of recipients, a standard similar to that for annual influenza vaccines. But that criterion has
not been changed. If the pandemic surges further, should a vaccine be approvable if it pre-
vents infection in a lower proportion of people? Health authority should make it a compul-
sory vaccination drive in selected sites, and the approved vaccines must be used to curb the
SARS-CoV-2 Virus. COVID-19 would be a serious debatable issue to maintain confidential-
ity in public health concerns. The FDA also cited the possibility of less conventional
approaches. One approach was allowed to know the “accelerated approval” of SARS-Cov-2
vaccines based on antibody levels or another biochemical marker rather than actual clinical
outcomes (Lam, 2000). These findings were expressed as “additional understanding of
SARS-CoV-2 immunology, and specifically, vaccine immune responses found to be reason-
ably more likely to predict protection against COVID-19 pandemic (immunity was acquired
from the infected person).” For many, the agency has shown increased willingness to
approve medications based on their capacity to affect surrogate measures such as laboratory
test results, rather than demonstrating the effect on clinical diseases. Such kind of approvals
was made for drugs with extremely limited patient outcome evidence in the discipline of
oncology and muscular dystrophy, among other conditions. Some have argued that extreme
clinical need warrants backing away from the FDA’s historical standards requiring clinical
benefits (Lu et al., 2020). This trend coincides with the increasing political popularity of the
libertarian “right to try” movement for medications, which advocates that patients should
be able to access treatments not approved by the FDA (Lu et al., 2020). This approach was
likely reflected in the presidential reasoning about unproven COVID-19 treatments: “Try it;
what do you have to lose in the policy at the population level.” Alternatively, the FDA noted
that it could implement an Emergency Use Authorization (EUA) to make a COVID-19 vac-
cine available even before its full evaluation is completed. This would have seemed implau-
sible but for the agency’s issuance of another COVID-19-related decision in March 2022
(World Health Organization, 2022). In the context of President Trump’s persistent advocacy
for hydroxychloroquine, the agency issued an EUA, making millions of doses available for
this purpose. That decision was eventually rescinded, but led to considerable use of the
drug, which continues, and the widespread misperception that the FDA had “approved”
hydroxychloroquine for this use. The FDA vaccine guidance acknowledged that an EUA
issued before completion of planned clinical trials “could reduce the ability to demonstrate
the effectiveness of the investigational vaccine in a clinical disease endpoint efficacy trial to
support the licensure for infected and exposed population”. A similar issue arose with con-
valescent plasma donated by COVID-19 survivors. The Donald Trump administration
established a program to provide convalescent plasma through an “expanded access” pro-
gram outside ongoing randomized clinical trials, likely reducing enrolment in the studies
required to determine if this therapy is effective and safe. A planned FDA EUA for plasma
was initially blocked by senior government scientists who cited the lack of adequate efficacy
data. President Trump then expressed concern that influencers within the FDA were trying
to delay COVID-19-related approvals until after the election to harm him politically.
Immediately thereafter, the FDA reversed its decision on convalescent plasma and autho-
rized an EUA for it, apparently without additional trial outcome data to justify this move.
Other concerning regulatory decisions by the FDA at a time of enormous pandemic-driven
pressure included its early hesitancy to approve tests to determine the presence of severe
acute respiratory syndrome coronavirus 2 (SARS-CoV-2), followed by widespread authori-
zation of other tests with widely varying accuracy. Just as the question “Does the vaccine
work?” does not have a simple binary outcome as answer, neither does the question “Is the
vaccine safe enough?” This will depend on the incidence and prevalence of COVID-19 in a
given place and time, as well as the quality of available therapeutics. What about a vaccine
that is effective in reducing infection, but produces a severe allergic reaction in 1.0% of
recipients, or one that causes anaphylaxis in 1 in 1,000 recipients, or 1 in 10,000. However, the
extremely rare but potentially catastrophic possibility of immune enhancement must also
be considered, in which disease is made substantially worse in some patients who receive a
vaccine even as it protects others (Basavarajaiah and Narasimha Murthy, 2020). We find
severe rare adverse events and require the study of tens of thousands of patients, but this
requirement will not be met by early adoption of a product that has not completed its full
trial evaluation (Basavarajaiah and Narasimha Murthy, 2020). This concern is even greater
for new molecular approaches that have never been used in any prior vaccine, produced by
manufacturers that have never brought a vaccine (or any other product) to market. Based on
the suggestive trend of biomarker assay, the antibody levels increased before the clinical
trial end. The research point data was completed and clearly depicted that the FDA approved
on October 2021 authorized limited “emergency” use of the drug in the high-risk subset of
the population (for example, healthcare workers or nursing home residents). The FDA con-
ducted feedback survey for the assessment of efficacy and safety of SARS-CoV-2 drugs.
Then-FDA Commissioner Stephen Hahn maintained that any vaccine “authorized for
widespread use will meet the appropriate standards for quality, safety, and efficacy” and
noted a distinction between “emergency use” and “final approval,” suggesting that the cri-
teria for an EUA could well differ from those for standard approval. The late-August 2021
plasma EUA decision was cause for alarm in this regard. Standards for efficacy and safety
must be high for any product designed to be administered to millions of healthy individuals
in the hope that it will prevent illness in a fraction of them. The calculus is particularly chal-
lenging when such infection is often asymptomatic, sometimes mild, but in some cases
fatal. The stakes are significantly higher if the decision must be made at a time when the
public is experiencing increasing anxiety over the pandemic, by a federal agency under the
jurisdiction of a president facing an imminent election who is not known for his under-
standing of or respect for scientific rigor. The public is not likely to focus on subtle distinc-
tions between antibody levels and clinical end points, or on the difference between
emergency authorization and full FDA approval. An October 2021 EUA based on suggestive
surrogate markers may give rise to an unjustified sense of “mission accomplished,” a risky
strategy for the nation. Vaccine use under an EUA could also miss the opportunity to learn
about the safety and risks of the vaccine in its earliest use, a problem that has occurred with
remdesivir and could undermine the completion of randomized trials, as well as the pub-
lic’s use of established measures, such as masks and distancing, that actually do prevent the
disease. If the FDA declined to issue the October 2021 EUA for a COVID-19 vaccine, the
agency could conceivably be directed to do so by the secretary of Health and Human
Services, or possibly by the president. Such a political intervention occurred in 2011 when
the secretary of Health and Human Services reversed an FDA commissioner’s decision to
make the “morning-after” contraceptive pill available over the counter to patients of all
ages. This type of political interference could not occur again. The approval or emergency
authorization of any COVID-19 vaccine will just mark the start of a second, equally crucial
phase: its deployment across an enormous population. This will be the largest vaccine
launch to take place in a period of unprecedented “vaccine hesitancy” by the public. In one
large recent survey, only 44% of 34,269 respondents said they were willing to get a COVID-
19 vaccine. If an approved vaccine reduces disease risk by 50% and is used by less than half
the population (as occurs each year with influenza immunization), it is unlikely to achieve
the herd immunity that many anticipated from a product expected to “reopen the country.”
If premature authorization leads to an overestimation of its effectiveness or failure to antici-
pate serious adverse effects, either misstep could damage the already delicate trust many
people in the USA have in immunization programs (Remme et al., 2010). The resulting dam-
age to public acceptance could represent a dangerous “adverse effect” of any vaccine pro-
gram, potentially undercutting all the excellent science and expense that preceded it
(Remuzzi and Remuzzi, 2020). However, FDA established a well-developed, science-based
approach to vaccine approval and surveillance. It rigorously presented sensible plans for
evaluating COVID-19 candidate products, but also we noted the possibility of approaches
using an EUA or accelerated approval based on surrogate measures even before ongoing
randomized trials are completed. The political and economic pressures on the agency in
October 2021 was unprecedented. But the nation’s health will be far better served by reliance
on the usual rigorous approach to vaccine evaluation. A premature rollout before the
planned trial data are even collected would not be a medical breakthrough; it could repre-
sent major public health missteps.
1. India’s legal framework for PHEs.

2. India does not have a single, consolidated PHE preparedness and response code.
3. Legal provisions relating to PHEs are scattered across a range of central and state
authorities.
4. Laws, including laws focused on epidemics, infectious diseases, and disaster.
5. Management laws, public health legislation, and criminal laws.
Two central laws, the Epidemic Diseases Act and the Disaster Management Act, dominate
the legal framework of PHEs. When analyzed using the duty-power–restraint frame-
work, (i) the Epidemic Diseases Act only confers powers, without creating obligations or
accountability or imposing restrictions on government (these themes were largely rep-
licated in state regulations issued under the Act during the COVID-19 pandemic), and
(ii) the Disaster Management Act provides for government powers and duties to manage
disasters, but is not a PHE-focused law and, therefore, does not provide for PHE prepared-
ness and response measures (Basavarajaiah and Narasimha Murthy, 2020). However, these
past legislative proposals are very relevant to public health emergencies ranging from a
targeted PHE law to general rights-based legislation, and comprehensive state law on pub-
lic health. Of these, the central PHE-specific bill is extremely limited in scope in that it
only deals with the power component of the duty–power–restraint framework. In India
context, the response to the COVID-19 pandemic several of the events that unfolded dur-
ing the COVID-19 pandemic further containment the combined framework of existing
legal provisions and periodic executive orders appeared to cover the basic aspects of con-
tainment measures, but the outcomes included inconsistent implementation across states,
confusion and misinformation, and frequent violations by the public. Quarantine and
isolation and contact tracing efforts fell short because of capacity constraints. Healthcare
workers went on strike to protest about the lack of protective equipment, people actively
avoided and absconded from unhygienic and ill-equipped isolation and quarantine cen-
ters, and digital monitoring efforts were legally opposed for their lack of privacy safe-
guards. Testing followed a delayed start, and the testing strategy eventually instituted
was restrictive and likely masked the actual incidence of the disease in the population
in the initial months; during this time, the exclusion of the private sector from testing
exacerbated capacity constraints, and the administration see-sawed on the subject of pric-
ing, leading to litigation. Furthermore, authorities’ ambiguity and capacity regarding the
statutory authority, functioning, and respective roles of the central bodies tasked with
orchestrating the pandemic response raised questions as to the legal basis and authority of
their directives and required judicial intervention. Inconsistent treatment and premature
advisories regarding treatments and protocols put patients and healthcare workers at risk;
vagueness and opacity surrounding the regulatory procedures followed for the approval
of vaccines led to public concerns regarding their safety and efficacy; in the absence of
appropriate protocols, attempts to arbitrarily regulate pricing, and failure to provide gov-
ernment funding options for treatment in private healthcare facilities resulted in public
hardship when seeking treatment, which once again required the courts to intervene.
While it is impossible to draw clear causal links between the bottlenecks in the response
discussed above, and the absence of a more comprehensive PHE law, the importance of
clarity and certainty through a legal framework on PHEs cannot be overstated. The exist-
ing Indian legal framework on PHEs, therefore, needs to be re-evaluated to address its
various shortcomings and incorporate the necessary aspects of modern PHE legislation in
a manner appropriate to the Indian context. The various issues that should be considered
include the scope of PHE legislation at the center: whether it is restricted to international
obligations or includes domestic administrative responsibilities; the need for state-specific
legislation, and the principles for division of responsibilities between the different tiers
of government; the capacity of the existing administrative infrastructure to handle PHE

preparedness and response activities, demarcation of responsibilities, and institution of
coordination mechanisms; structuring of legislation the content and levels of specificity in
primary and secondary legislation, and the status of PHE protocols vis-à-vis the law; the
structure, functions, and purview of monitoring and accountability mechanisms; and the
nature and framing of rights under a PHE law, including the necessary level of specificity,
the rationale for the inclusion of corresponding duties, and the nature and accessibility of
remedies for violations. This exercise will require expertise and consultation with appro-
priate stakeholders from the government, public health and policy sector, civil society, and
vulnerable groups that have been particularly affected by COVID-19.
11.5 Methods of Formulation of Policy Based on

Different Social and Economic Attributes
Policy implication methodology is important domain to develop a flawless or techni-
cally sound explicit policy in terms of its epidemiology limitations, evidence base, socio-
cultural acceptance, and political sensitiveness. Methodological considerations are the
following: (i) need assessment: This is basically done by epidemiological methods for
health needs assessment (estimates such as the prevalence of illness) and social science
methods and community need assessment and rapid appraisal techniques for health-
related outcomes and quality of life. (ii) Assessment of resources by a situation analysis
or gap analysis can be done sector-wise fiscal/human resource inventory, for areas of
content. (iii) Other specific methods used in economics that are needed are prioritization
and quantitative techniques such as modeling. Broadly, this approach or perspective can
be analyzed at stakeholder level or national/state/micro- or macro-level or at domain or
content levels (sectorial policies) or from the perspectives of groups such as minorities,
especially disadvantaged groups. (iv) Specific methodologies of social science, such as
a case study, comparisons of worst-case and best-case scenarios, network or path analy-
sis, and pictorial depictions such as network models, can be employed. Involvement of
public in the policy development process or ensuring pro-people nature is required. (v)
Quantitative techniques such as microsimulation are important for impact evaluation.
Health policy as a part of public policy and the six key characteristics of public pol-
icy are applicable in this regard also. These are strategic, outcome-focused, joined-up,
inclusive, flexible and innovative, and robust nature of the policy. Now, 14 years after
the last health policy, the context has changed in four major ways. First, health priori-
ties are changing. Although maternal and child mortality has rapidly declined, there
is a growing burden on account of non-communicable diseases and some infectious
diseases. The second important change is the emergence of a robust healthcare industry
estimated to be growing at double digits. The third change is the growing incidences of
catastrophic expenditure due to healthcare costs, which are presently estimated to be
one of the major contributors to poverty. Fourth, the rising economic growth enables
enhanced fiscal capacity. Therefore, a new health policy response to these contextual
changes is required. The primary aim of the National Health Policy, 2017, is to inform,
clarify, strengthen, and prioritize the role of the government in shaping health sys-
tems in all its dimensions—investments in health, organization of healthcare services,
prevention of diseases, and promotion of good health through cross-sectoral actions,
access to technologies, developing human resources, encouraging medical pluralism,

building a knowledge base, developing better financial protection strategies, strength-
ening regulation, and health assurance. NHP 2017 builds on the progress made since
the last NHP 2002. The developments have been captured in the document “Backdrop
to National Health Policy 2017—Situation Analyses” (Ministry of Health and Family
Welfare, Government of India). Communicable diseases: The policy recognizes the
interrelationship between communicable disease control programs and public health
system strengthening. For IDSP, the policy advocates the need for districts to respond to
the communicable disease priorities of their locality. This could be through a network of
well-equipped laboratories backed by tertiary care centers and enhanced public health
capacity to collect, analyze, and respond to disease outbreaks.
11.6 Practical Approach to Implementation of Health Policy

A key challenge faced by the global health community is how to take proven interventions
and implement them in the real world. Affordable, life-saving interventions exist to con-
front many of the health challenges we face, but there is little understanding of how best to
deliver those interventions across the full range of existing health systems and in the wide
diversity of possible settings. Our failure to effectively implement interventions carries a
price. Each year, more than 287,000 women die from complications related to pregnancy
and childbirth, for example, while approximately 7.6 million children, including 3.1 million
newborns, die from diseases that are preventable or treatable with existing interventions
(WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division,
2019.). While understanding implementation in the real world, implementation issues arise
as a result of a range of factors, including “real-world” contextual factors that are either
overlooked or not captured by other research disciplines. Implementation research shines
a light on those factors, providing the basis for the kind of context-specific and evidence-
informed decision making that is crucial to making what is possible in theory a reality in
practice. Because implementation research is embedded in reality, people working in the
real world (practitioners as opposed to people “doing research”) often ask the questions
that are the starting point for new thinking. Making sure that those questions are heard,
and that the research undertaken is directed at finding answers to the questions asked
rather than at the topics researchers themselves may find interesting is one of the key
challenges implementation researchers face. A practical tool embedded in the real world,
implementation research is also a powerful tool for capturing and analyzing informa-
tion in real time, allowing for the assessment of performance, for example, and facilitat-
ing health systems strengthening. Implementation research is particularly important in
supporting the scale-up of interventions and their integration into health systems at the
national level. Too often interventions that work in small-scale pilot studies fail to live up
to expectations when rolled out in national strategies or fail to transfer from one country
to another as a result of contextual differences. Implementation research not only helps to
clarify why that happens, but can be used to support the process of reiterative refinement
needed for successful adaptation. The same capacities make implementation research
a useful tool for helping organizations develop the capacity to learn, enabling them to
assimilate and put into effect knowledge developed on an iterative basis.
11.6.1 A Collaborative Endeavour

Implementation of research is often most useful where implementers have played a part
in the identification, design, and conduct phases of the research undertaken. It is for this
reason that the fostering of collaborative ties between key stakeholders involved in policy
generation, program management, and research is so important. One way to support col-
laboration between researchers and implementers is to integrate implementation research
into policy and programmatic decision-making processes right from the beginning,
rather than an endeavor that is carried out separately from the implementation process.
In this way, scientific inquiry can also be integrated into the implementation problem-
solving process in an iterative and continuous manner. Implementation research can also
play an important role in acting as a vehicle for grassroots communities by identify-
ing neglected issues, exposing performance shortcomings, and increasing the account-
ability of health organizations. In all of these collaborative endeavors, i mplementation
researchers are called upon to be receptive and flexible in the work they do. Indeed, the
understanding of context and systems, and the flexibility to identify appropriate meth-
odological approaches, can be as important as or even more important than adherence to
a fixed research design.
11.6.2 A Broad Research Spectrum

Broadly speaking, the term implementation research describes the scientific study of the
processes used in the implementation of initiatives as well as the contextual factors that
affect these processes. It can address or explore any aspect of implementation, includ-
ing the factors affecting implementation (such as poverty, geographical remoteness, or
traditional beliefs), the processes of implementation themselves (such as distribution
of fully subsidized insecticide-treated bed nets (ITNs) through maternal health clinics,
or the use of mass vaccination versus surveillance/containment), and the outcomes or
end products of the implementation under study. Implementation research is applicable
and relevant to many different research domains, and to different degrees, depending
on the subject under study. For example, basic research into new medicines typically
involves no implementation issues, while ensuring that those medicines are available to
the people who need those do. Implementation research often focuses on the strategies
needed to deliver or implement new interventions here called “implementation strate-
gies,” a term used to distinguish them from clinical and public health interventions. In
order to study implementation processes, a framework for conceptualizing and measur-
ing implementation outcomes based on variables such as “acceptability,” “appropriate-
ness,” and “feasibility” can be used to understand how well a given implementation
process is actually working. Because it draws on a wide variety of research approaches
and disciplines, it makes little sense to talk in terms of a set of “implementation research
methods.” However, certain research approaches and designs—including pragmatic
trials, effectiveness–implementation hybrid trials, quality improvement studies, and
participatory action research—are particularly useful because they generate actionable
intelligence, are good at capturing the subtleties of context over time, and offer iterative
flexibility needed to respond to change. While such tools are vital to the implementation
researchers, it is important to bear in mind that in implementation research, the “ques-
tion is king,” which is to say that it is the question that determines the method used,
rather than the method that determines the kinds of questions asked. Implementation
research questions are often complex, reflecting the wide array of contextual factors that
can influence implementation, producing unpredictable effects, and requiring continu-

ous adaptation by implementers. Embracing that complexity requires considerable flex-
ibility on the part of researchers, particularly in regard to the complex and dynamic
nature of the subject under study.
11.7 Aligning Research with Need and Ensuring Quality

Ideally, implementation research should be aligned with need in the sense that it both
addresses the concerns of the intended audience and is also responsive to the particulari-
ties of the subject under study. A key consideration in this regard is the level of certainty
required regarding results or projections. A policy maker working with his or her own
constraints, for example, may be looking for strong indications that a given intervention
will work, but may not necessarily have the time required for multi-year studies that could
generate a higher level of certainty. Responding to the needs of different audiences may
have important implications for the basic design of research, and for budget and schedule.
In order to ensure that implementation research is aligned with need and of high quality,
it is helpful to ask the following key questions:
i. Does the research clearly address a question concerning implementation? Is there

a clear description of what is being implemented (e.g., details of the program, prac-
tice, or policy)?
ii. Does the research involve an implementation strategy—if so, is it described and
examined appropriately?
iii. Is the research conducted in a real-world setting? If so, are these conditions
described in sufficient detail?
iv. Does the research appropriately consider implementation outcome variables?
v. Does the research appropriately consider context and other factors that influence
implementation?
vi. Does the research appropriately consider changes over time, and the level of com-
plexity of the system?
vii. Does the research clearly identify the target audience for the research and how it
can be used?
Getting more out of implementation research: Despite the importance of implementation

research, it continues to be a neglected field of study, partly because of a lack of under-
standing regarding what it is and what it offers, and partly because of a lack of investment
in implementation research activities. We spend billions on health innovations, but very
little on how best to use them. This problem affects everyone, but in particular populations
in low- and middle-income countries (LMICs) where the implementation challenges are
greatest. This guide is an attempt to redress the deficit in the understanding of implemen-
tation research and to encourage program personnel and implementers to take a greater
interest in the subject, recognizing that implementation research is in fact an integral part
of program planning and execution, rather than something that happens once programs
are up and running, and conducted largely for the benefit of other researchers. For their
part, implementation researchers can do much more to engage with implementers and
program personnel in the research process. Only by coming together can implementers,
with their intimate understanding of context, and researchers, with their understanding of
the methods and science of inquiry, hope to advance our understanding of the implemen-
tation issues that compromise so many of our public health endeavors.
11.8 Government and Public Responsibilities to Safeguard

Policy During an Emergency Situation
Health policy and systems research (HPSR) is an emerging field that seeks to understand
and improve how societies organize themselves in achieving collective health goals, and
how different actors interact in the policy and implementation processes to contribute to
policy outcomes. By nature, it is interdisciplinary, a blend of economics, sociology, anthro-
pology, political science, public health, and epidemiology that together draw a compre-
hensive picture of how health systems respond and adapt to health policies, and how
health policies can shape and be shaped by health systems and the broader determinants
of health. HPSR can be employed at several points in the policy cycle, from getting an
issue onto the policy agenda to evaluating and learning from implemented policies. In
this way, HPSR is characterized not by any particular methodology, but by the types of
questions it addresses. It focuses primarily upon the more upstream aspects of health,
organizations, and policies, rather than clinical or preventive services or basic scientific
research (for example, into a cell or molecular structures). It covers a wide range of ques-
tions—from financing to governance—and issues surrounding the implementation of
services and delivery of care in both the public and private sectors. It is a crucial policy
analysis tool on both policies and processes—including the role, interests, and values of
key actors at local, national, and global levels. The appropriate mix of disciplines to be
used in HPSR depends largely on the nature of the research question being addressed
(Thaddeus, 1994). An evaluation of a health insurance scheme might draw upon economics
to understand the financial consequences of the scheme and its impact upon demand for
services, anthropology to understand various socio-cultural and organizational aspects
as well as patterns of consumption, and epidemiology to understand its health conse-
quences. HPSR can address any or several of the health systems’ building blocks and their
ultimate objective is to promote the coverage, quality, efficiency, and equity of health sys-
tems. In doing so, it acknowledges the inherent connections and dynamics among the
different building blocks in assessing and understanding how interventions might play
out across them. It also seeks to unpack the behavior, reactions, and interconnectedness of
health systems and the people within those systems. The way HPSR conceptualizes and
analyzes these interactions helps to illuminate not only what works, but for whom and
under what circumstances. HPSR and the building blocks of a health system link health
policy with health systems research. Why health policy and health systems research? Why
these two different domains are fused intone? While seemingly separate—with health
policy research principally studying how different factors interact in the policy and imple-
mentation processes and contribute to policy outcomes, and health systems research
addressing questions such as the coverage, quality, efficiency, and equity of health sys-
tems—the two have clear and multiple synergies: Health policies are subject to political
processes that govern health systems. Understanding these processes is critical not only
in the design of effective policies, but also in the creation of evidence to inform those poli-
cies. Health policies and health systems are not separate entities: HPSR is recognition that
everything is connected. Understanding the processes and dynamics of health systems
can directly inform policy making and decision making. Active linkage and exchange
between health system researchers, decision makers, and other research users promote
evidence-informed policy and policy-informed research. A systems perspective is critical
in evaluating and learning from implemented policies. Removing both from their silos
builds the capacities of key actors in health policy, in health systems research, and creates
actors versed and able in both.
11.9 How to Formulate Health Policy Research

Unlike medical research, health research is comparatively a new concept. It goes beyond
illness to include the research into the various determinants of illness as well as health.
Health research, therefore, is the systematic generation of knowledge that can be used
to promote, restore, maintain, and/or protect the health of individuals and popula-
tions. The establishment of a Department of Health Research (DHR) in the Ministry of
Health is recognition by the GOI of the key role that health research should play in the
nation. This decision was preceded by the Report of India’s National Commission on
Macroeconomics and Health (NCMH), which builds a strong case for investing in indig-
enous research and encouraging Indian companies and universities in a partnership to
engage in R&D for drugs, medical devices, and vaccines relevant to the needs of India’s
poor. For developing a culture for research, the report suggests that the government
should initiate steps to de-bureaucratize procedures, introduce greater transparency,
and provide incentives and adequate flexibilities to enable engaging and retaining the
best minds to undertake research—in both public and private universities and research
institutions. The weakness of the publicly funded health structures and the research
infrastructure is a key limiting factor in realizing the full benefits of this commitment to
research. The fact that the almost 300 medical colleges in the country are not contribut-
ing their best to health research is highlighted by the fact that in 2007, 96% of the research
publications in India emanated from nine medical colleges. Much of this published
research is not on priority health concerns, and the translation of key research findings
into policy that could improve the health of the people is very limited and needs to be
enhanced. Epidemiological know-how, surveillance technology, and diagnostic services
which are essential for determining health priorities are very poorly developed. With
the launch of the National Rural Health Mission (NRHM) and the proposed National
Urban Health Mission (NUHM), the enhancement of the above-described infrastructure
to provide the evidence base for policy and program becomes a critical issue. There is
also a compelling need to build multidisciplinary research blending physical, medical,
and social sciences. Besides, there is also an equal urgency to establish regulations, strict
ethical norms, transparency, standardized methodology, and international standards of
research. Such capacity is necessary for undertaking operational research as also is the
large-scale evaluation of diagnostics and trials of drugs and devices of both modern
and traditional systems of medicine. It is in this context that the DHR has formulated a
National Health Research Policy. In India, while most of the agencies funding research
have plans in general linked to the national five-year plans, a coordinated national
health research policy that could guide the planning and implementation is not yet in
place. The increasing international collaborative research in priority areas of national
health also necessitates a clearly spelled-out policy to ensure that the contributions of
our international partners can enhance the ability of the partnership to improve national
health. Some of the conflicts and failures of Indian health research can be attributed to
the absence of such an overarching policy. Health is also now recognized as a fundamen-
tal issue in national development and a factor that promotes equity. A clearly defined
health research policy with a well-defined vision, mission, strategy, and deliverables,
therefore, is the basis for maximizing the return on investment in this important field.
It is imperative that such a policy will give special attention to the health problems of
socially underprivileged groups (tribes, women, and other marginalized groups) and
difficult-to-access geographical areas. The vision of National Health Research Policy is to
maximize the returns on investment in health research through the creation of a health
research system to prioritize, coordinate, and facilitate the conduct of effective and ethi-
cal health research and its translation into products, policies, and programs aimed at
improving health, especially of the vulnerable populations.
11.9.1 Objectives of the National Health Research Policy

The broad objectives of the National Health Research Policy are to identify priorities for
effective and ethical health research to enable the achievement of the objectives of NHP 2002,
NRHM, Bharat Nirman, and National Food Security Act as well as global commitments such
as MDG and IHR, ensuring that the results of health research are translated into actions.
i. Foster inter-sectoral coordination in health research including all departments

within the government, private sector, and the academia to promote innovation
and ensure effective translation to encourage/accelerate indigenous production of
diagnostics, vaccines, therapeutics, medical devices, etc.
ii. Focus on the marginalized, vulnerable, and disadvantaged sections of society.
iii. Strengthen national networks between research institutes, academia, and service
institutes, and encourage PPP.
iv. Put in place strategies and mechanisms for assessing the cost-effectiveness and
cost-benefits of interventions for health.
v. Develop and manage human resources and infrastructure for health research,
and ensure that international collaborative research contributes to national health.
11.10 Preparedness of Implementation Policy

11.10.1 What is Health Policy Implementation?
The process of policy implementation thus requires working with and through a set of
actors and organizations to communicate policy objectives, ensure availability of resources,
achieve ownership of the policy by implementers, manage conflict and cooperation, and
sustain policy changes.
11.10.2 What is the Importance of Policy Implementation?

It helps to identify how, when, and by whom implementation will be assessed. Monitoring
of implementation keeps everyone involved aware of any possible barriers as well as any
intended and unintended impacts of the work. After implementation, resources and other
supports from stakeholders may decrease.
11.11 How to Implement Effective Policies and Procedures

To implement effective policies and procedures at your workplace, follow these steps to
get the best results. As per MoHFW (2022), we can implement effective policies and proce-
dures at our workplace.
11.11.1 Consultation
When developing our policies and procedures, we must consult with all relevant stakehold-
ers, including health and safety representatives, contractors (particularly those who work
with you regularly), and of course our employees. Consultation should ensure that every
person in your workplace understands the importance of company policies and procedures
and why they need to be implemented effectively. It will also ensure that the policies and pro-
cedures are realistic and actionable on a daily basis. Tip: Consultation helps to achieve more
effective policies and procedures and is a greater motivation for employees to follow them.
11.11.2 Tailor the Policy to Your Business

The policies and procedures you adopt need to be tailored to the needs of your business, not
just be taken straight from a generic manual. If you use policies and procedures from another
source, it is essential that you adapt them to your company and your workplace operations.
11.11.3 Define Obligations Clearly be Specific

All policies should be short and succinct. All procedural steps should be set out in clear
and plain English.
This will create an “auditable standard,” meaning that you create a standard that can be
used to measure whether your workplace health and safety obligations are being met or
not. The obligations outlined in an auditable standard should be defined in enough detail
that persons in your workplace understand exactly what is expected of them. Specifically,
state what actions should be taken. For example, don’t say “dispose of chemicals safely,”
but state how this should be done at the site, e.g., “chemicals must be disposed of in the
designated approved dangerous goods waste drum.”
11.11.4 Make the Policy Realistic

Make sure your business has the time, resources, and personnel to implement the policy.
There is no point in adopting a policy that aspires to be the best practice possible if your
business cannot realistically adopt the procedures set out. This is the development stage
of the policy and procedure done. Once you have completed these steps, you will have the
policies and procedures your company needs to maintain a healthy and safe workplace.
But the next stage is just as important as the development stage, the implementation stage.
Don’t get too excited that you have developed the policies and procedures because without
implementing them correctly, they won’t be of any use to you.
11.11.5 Publicize the Policies and Procedures

Put your policies and procedures in writing, and make them available to your entire workforce.
If possible, keep all your policies and procedures in a single manual and make copies
readily available to all employees. Tip: Safety documents should also be published on the
company’s intranet if you have one.
11.11.6 Train All Employees in Policies and Procedures

Suppose we have an obligation to provide adequate information, instruction, supervision,
and training to your employees. Ensure that new employees and contractors are trained
and familiar with company policies and procedures, and that existing staff receives appro-
priate training, e.g., annual refresher courses. Policies and procedures should also be reiter-
ated and discussed with staff regularly at team meetings to ensure that employees remain
aware of the importance and advantages of the policies and procedures. Tip: It is a good
idea to have all employees and contractors sign off after they have read, understood, and
agree to comply with your workplace policies. We should also keep records of training and
induction and make sure that you record attendees and details of training content in case
an employee fails to sign a training record.
11.11.7 Be Consistent in Your Policy Implementation

Supervision of our work to ensure that the policies and procedures are being properly
implemented by all employees is essential. The follow-up ensures that any failure to follow
the policy or procedure is addressed. Specify that full compliance with the stated require-
ments is needed to ensure a safe workplace.
After this, any deliberate breaches of policies or procedures must be treated seriously and
dealt with immediately and consistently. All supervisors and managers must “lead by exam-
ple” in implementing policies and procedures. It is crucial that all OHS expectations are dem-
onstrated through modeling and leadership at all levels of management. If managers condone
practices that do not fall within the policy, it could be argued that disciplinary action against
an employee who fails to follow the policy is unfair. The consequence of any deliberate breach
should be appropriate to the severity of the breach of disciplinary action (e.g., a warning).
11.11.8 Review All Policies and Procedures Regularly

Policies and procedures must be reviewed periodically. When any changes occur, ensure
our policies and procedures remain relevant and effective. For example, a change may
occur when a business purchases a new piece of machinery, starts using a new chemical,
or adopts a new production method. Any such changes mean that relevant procedures
should be reviewed. Tip: The review cycle will depend on the circumstances and docu-
ment type, but it is a good idea to review policies at least every 2 years, e.g., an OHS train-
ing policy may only need to be reviewed every 3 years, but a chemical handling procedure
should be reviewed more often due to the level of hazard involved. Implement a docu-
ment management system that triggers reviews, notes the dates of change, and involves
interactive revision. All employees and contractors need to be made aware of the changes
to policy and procedure when they occur.
11.11.9 Enforce the Workplace Policies and Procedures

Once policies and procedures have been implemented, they need to be enforced. Make
sure that you approach this consistently as this is an important factor in being able to
discipline a worker for a breach of policy. Any policy effort to improve health system
performance must address the challenges of policy implementation. But health policy
analysis, in general, tends to emphasize issues of policy design and adoption over ques-
tions of policy implementation. Although these policy cycle phases may overlap and
share common challenges, a focus on policy implementation is still needed. This chapter
seeks to correct this gap in the literature. We build on existing knowledge about health
policy implementation in LMICs to propose a way of both identifying and address-
ing some of the central challenges. Policy implementation is a complex phenomenon
and cannot be adequately covered in a short paper. We, therefore, focus only on cer-
tain aspects of health policy implementation using the lens of political science. Even
this focus is not easy, however, in part because few political analyses have been con-
ducted of health policy implementation in LMICs. Basavarajaiah and Narasimha Murthy
(2020) examined one aspect of implementation: the politics of policy implementation
for the health sector, particularly the management of stakeholders in order to improve
the chances of achieving policy objectives. We provide a characterization of stakeholder
groupings that are relevant for all phases of policy reform, but we focus on the chal-
lenges for health policy implementation. Throughout this chapter, we refer to health
policy or health reform implementation with the understanding that health reform usu-
ally involves multiple policies seeking to achieve system-wide change (Walt et al., 2008;
Yazdani and Wells, 2018). By health policy, we mean a government decision and plan
of action to make progress toward the goals of the health system: improved population
health status, increased financial risk protection, and increased client satisfaction; or the
intermediate outcomes for health systems, under which we include quality, access, and
efficiency. The conceptual framework for this chapter draws on the theoretical literature
in political science and sociology while being practice oriented. This chapter is intended
to assist people tasked with strategic planning for health policy implementation; these
people include government policy makers and high-level implementers, but may also
include policy actors outside of government. They may belong to a stakeholder category
themselves. We call these people “policy implementers” or “change teams,” although, in
practice, they may not be officially formed teams with a clear implementation mandate.
Our argument, in short, is that a group of people need to plan for and manage health
policy implementation for it to be successful, and they will often confront political chal-
lenges in dealing with implementation stakeholders. This chapter may also assist those
responsible for designing health policy, in helping them anticipate implementation chal-
lenges that can be addressed in the design phase.
11.12 The Challenges of Implementing Health Policy

The implementation of a new health policy demands more than providing instruc-
tions around a policy document or designing a set of standard operating procedures.
An effective health policy implementation requires the aggregation of the separate actions
of many individuals, and an understanding to how and why the actions in question are
consistently reproduced by the behavior of individuals. One fundamental implementation
challenge is that the responsibility for health policy implementation usually rests with a
different set of governmental actors than the ones who designed the policy. Policy design-
ers often do not understand the perspective of the implementers. The process of policy
implementation thus requires working with and through a set of actors and organizations
to communicate policy objectives, ensure availability of resources, achieve ownership of
the policy by implementers, manage conflict and cooperation, and sustain policy changes.
We start a new program and maintain it; joint efforts and contributions from multiple gov-
ernmental agencies or private actors are needed. This frequently results in delays, renego-
tiation of resources and responsibilities, and confusion among the beneficiaries. In short,
implementation is messy.
To move health policy forward into practice, implementers must realistically consider
the difficulties of implementing a policy in their particular national context, viz. (i) policy
implementers or change teams need to recognize the complexities and characteristics of
the administrative context in which their policies will become operational; (ii) those lead-
ing policy implementations need “persistence, discipline, and rigor” to work within their
particular contexts, and they need to make difficult decisions regarding staffing, organi-
zational structure, and relationships with stakeholders to make policy implementation
happen.
11.12.1 What Happens During Policy Implementation?

Policy implementation involves translating the goals and objectives of a policy into action.
But some practical strategies are suggested to overcome implementation performance and
conclude with the proposition that implementation failure is also due to a lack of theoreti-
cal sophistication.
11.12.2 Who Is Involved in Policy Implementation?

Government policy is often articulated as high-level goals and objectives. A range of stake-
holders are involved in implementation, for example, institutions, agencies, service provid-
ers, and intermediary organizations, before they have an impact on citizens. What are the
three elements of policy implementation, bringing them back to the three basic elements,
i.e., actors, resources, and institutions?
11.13 Pilot Study for Implementation Policy

11.13.1 What Is a Pilot Implementation?
The pilot project is an initial small-scale implementation that is used to prove the viability
of a project idea. This could involve either the exploration of a novel approach or a new
idea, or the application of a standard approach recommended by outside parties, which is
new to the organization.
11.13.2 How Do You Implement a Pilot Program?

After you’ve decided on the technology you want to test, you can start organizing your
pilot program with these steps:
• Set clear goals.

• Decide on a length of time.
• Choose your testing group.
• Develop a plan for onboarding.
• Get feedback.
• Address challenges.
11.14 What Are Pilot Studies Used For?

Pilot studies represent a fundamental phase of the research process. The purpose of conduct-
ing a pilot study is to examine the feasibility of an approach that is intended to be used in a
larger-scale study. The roles and limitations of pilot studies are described here using a clinical
trial as an example. Pilot studies are an important component of the innovation process. They
play a key role in the development and refinement of new service interventions and the adop-
tion of new technologies. Pilot studies are used to evaluate activities such as the feasibility of
recruitment, assessment procedures, new methodologies, and the introduction of new service
improvements. The component(s) of the pilot found to be unsatisfactory can be modified or
removed from the subsequent main project. In addition, a pilot study provides the opportu-
nity to develop more consistent practices to increase data integrity and decrease the risk for
patients. These good clinical practices include such things as better data collection systems,
better-informed consent practices, robust monitoring and oversight procedures, and regula-
tory reporting processes. Pilot studies are exploratory and proof-of-principle projects; they do
not perform hypothesis tests. Typically, data generated by a pilot are not combined with the
data collected from the subsequent much larger main project. This is because it is likely that
the methods employed in the main study have been adapted or even radically changed since
the pilot. Such changes in the methods risk adding additional probably unknown sources of
variation that could compromise the findings of the main study. To implement a pilot study,
you should consider a model of improvement, and a tried and testing method of doing so is
the plan–do–study–act, or PDSA, Cycle. This is an easy-to-use tool to help implement and
evaluate pilot studies. We will look at the PDSA cycle, but for now, when designing and
implementing a pilot study, consider some fundamental questions such as the following.
11.14.1 What Are You Trying to Achieve?

It is important that you, and your team, know what you are trying to achieve. This informs
the aims and objectives for your pilot study.
How will you know your innovation is an improvement as not all change is necessary
for the better?
What will you measure and how? Think back to how you measured your current ser-
vice. What is your criterion for success? For example, a 20% reduction is the turnaround
time for thyroid function test requests from primary care.
What changes can we make that will result in an improvement?
What have others done? What have you and your team brainstormed for example? What
has your process mapping exercise highlighted as problems?
At this stage, it is about testing on a small scale. Consider, for example, using interviews
with key stakeholders (including, where appropriate, patients). Also, use volunteers and
colleagues to test your ideas. Find out what their thoughts on your changes are, whether
they will work, and whether they will be an improvement. As you are testing on a small
scale, use only one location.
In the next step, we will consider methods of evaluating your pilot study. Do you already
know which evaluation tools you would use in your innovation? Share your ideas via the
comments section.
11.15 Formulation of Uniform Civil Code to Frame

Health Policy During the Pandemic Crisis
A perusal of the constitutional scheme suggests that state governments are solely respon-
sible for pandemic control within their state and the central government must provide
assistance on a macro-scale, to prevent inter-state transmission of the disease. In contrast,
the central government’s COVID-19-related notifications reveal an encroachment on state
government powers. For example, the guidelines accompanying the declaration of the first
lockdown in India dated March 24, 2020, make regulations related to, inter alia, hospitals
(explicitly covered by Entry 6 on the State List), markets (expressly included in Entry 52
on the State List), and state government offices (covered by “State Public Offices” Entry 41
on the State List). Similar encroachments may be found in subsequent guidelines issued
along with subsequent extensions of the lockdown. In accordance with Articles 73 and 162
of the Constitution, the executive powers of the central and state government are coexten-
sive with their legislative powers. The central government’s guidelines, therefore, invaded
aspects of governance that fall within the exclusive domain of the state governments.
Moreover, the Constitution of India does provide a mechanism for the central govern-
ment to legislate (and consequently regulate) matters covered by the State List, allowing
for flexibility when matters extend beyond the purview of the state governments. Article
249 of the Constitution permits the central government to legislate on subjects contained
in the State List as long as it is in the national interest. One could argue that responding
to an unprecedented outbreak of a pandemic is a matter of national interest. However, to
do so, the Council of States must pass a resolution, finding it is necessary, or expedient in
the national interest, that the Parliament ought to legislate on a matter enumerated in the
State List. Such a resolution must receive the support of at least two-thirds of the members
present and voting. In this instance, there does not appear to be a resolution allowing
the central government to act in the manner in which it is. The constitutional propriety
of the central government’s response to the COVID-19 pandemic is questionable, which
begs the question of why there has been a lack of protest from the states. But acquiescence
is characteristic of Indian federalism, which relies on having a strong center and subor-
dinate states. In Union of India vs State of Rajasthan, Indian federalism was described as
“watered down.” In State of West Bengal vs Union of India, the Supreme Court described
Indian federalism as being where “the political sovereignty is distributed between…
the Union of India and the States with greater Weightage in favour of the Union.” This
is very unlike the American notion of federalism. The lack of protest against the central
government’s encroachment upon state powers may be attributable to this conventional
understanding of the subordinate role of states within the Indian federation.
11.16 Propagation of Public Feedback for Policy Implementation

Former American President Donald Trump argued and delivered a speech on control
measures and policy intervention of SARS-CoV-2. The rapid transmission of the virus
drew his attention and impressions. In his speech, how COVID-19 has been handled
over the last 6 months reflected on the formulation and implementation of public pol-
icy. COVID-19 caught every public authority by surprise. No one was prepared for
the speed of its diffusion, the virulence of its impact, the “known unknowns” of its
duration, and the ethical conundrums raised by the debate over “lives” and “liveli-
hoods.” The initial response of the Indian authorities was swift and a surgical national
lockdown was announced following a 4-hour notice, but thereafter, the policies were
made on the hoof, understandable perhaps, given the nature of the raging virus and
the spread of poor, at times misleading, data and deepening public anxiety. The results
have been mixed. Some authorities were relatively successful, and others clearly lost
control. This raises the question: Are there factors beyond the state of the public health
infrastructure and the medical advice to “test, trace, and isolate” that explain these dif-
ferences in results? What lessons learned bySARS-Cov-2 and how this experience offer
the practitioners of public policy the benefit of 6 months of hindsight and implementa-
tion of new health policy. We discern two public policy-related learnings and offer one
suggestion: One, governments cannot, on their own, manage such a crisis. They do
not have the technical, scientific, or even institutional tools to tackle such “invisible”
black swan occurrences. They need the support of outsiders on the global platform.
The paradox that at a time when populist leaders are hunkering down behind protec-
tionist walls, the corporates are decoupling their supply chains, and nationalism has
become the byword of global geopolitics, COVID-19 has brought into sharp focus the
importance of collaboration and partnerships. It has compelled even the most nativ-
ist of politicians to accept that the fight against this virus can only succeed if tal-
ent and Intellectual people are free-flowing and fungible, the distribution chain was
linked and seamless (imagine the logistic hurdles of trying to vaccinate billions in the
absence of such a link), and the wedge dividing the world was loosened. Two, lessons
learned in tackling the SARS-CoV-2 viz. managing the health crisis which depends on
disentangling policy formulation from policy implementation. The two are, no doubt,
connected, but they must be looked at through different lenses. Policy formulation
requires an understanding of the nature of the problem, the development of options,
the risks associated with each option, and then a decision on the preferred pathway.
Policy implementation, on the other hand, must get into the roots. It requires a com-
prehension of the local context, the evaluation of the capacity to deliver, the identifica-
tion of the obstacles, and the steps needed to remove them. Given the diversity of the
nation, a policy formulated at the national level seldom shows the purpose of imple-
mentation across the country. At most, the policy provided a framework for local lead-
ers to use in crafting contextualized implementation plans. In the past few months,
the policy empowered to implement development programs without hindrance in a
relatively more successful manner than those shackled by the distraction of intrusive
bureaucratic oversight. The political pressures met the targets regarding testing, avail-
ability of beds, the dispensation of PPEs, etc., and those who were insensitive to local
factors (Figure 11.3).
COVID-19
FIGURE 11.3
COVID-19 NHP—different criteria.
11.17 Barriers for Implementing Public Health and

Social Measures to Prevent COVID-19
Barriers that hinder the implementation of PHS measures to prevent COVID-19 are the
following.
11.17.1 Lack of Safety Commitment from Public (Br-1)

Commitment is a force that binds an individual to a course of action of relevance to one
or more targets [11]. Safety commitment from public refers to the fervor in the adoption
of PHS measures as per the guidelines issued by the WHO to prevent the transmission of
COVID-19. Proper knowledge of novel coronavirus among public and awareness of WHO
regulations boost the safety commitment from public. Lack of commitment from public or
public resilience would result in an increase in transmission rates.
11.17.2 Poor Safety Culture (Br-2)

A safety culture is a culture of government that puts a strong degree of emphasis on pro-
tection principles, values, and attitudes, and these are shared by most of the citizens in the
region. Safety culture is defined as the set of beliefs and social and technical practices that
are concerned with minimizing the exposure of people to conditions considered danger-
ous. Poor safety culture would result in giving less preference to the prevention and safety
measures shared by the WHO in containing the spread of COVID-19.
11.17.3 Lack of Administrative Commitment and Support at Community Level (Br-3)

The prevention strategies profoundly depend on administrative support, which is neces-
sary for the maintenance, participation, and motivation in implementing the COVID-19
prevention process. The commitment from local administration by creating opportunities
to facilitate the lockdowns ensures the basic necessities to be provided to common people
to restrict their movement. As per WHO guidelines, lockdowns are necessary to prevent
the transmission rate of COVID-19 outbreak and local administrations need to impose
restriction on accessing the public places.
11.17.4 Lack of Strict Enforcement of WHO Regulations (Br-4)

The strict enforcement of WHO regulations would only be possible by informing peoples, offi-
cials, and leaders about WHO regulations. Some of the regulations and recommendations pro-
vided by WHO [16] to minimize the risk of transmission of COVID-19 disease are as follows:
a. Evading close interactions with people infected with COVID-19.

b. Ensuring frequent handwashing, exclusively after direct contact with infected
people.
c. Advising the people suffering from respiratory infection to maintain proper
hygiene while coughing and sneezing.
If the regulations provided by WHO are not followed properly, the COVID-19 pandemic
will contribute more to public hazard and, therefore, more transmissions and loss of lives
will follow. Enforcement of strict social distancing measures may assist in limiting the
spread of COVID-19 disease. The quarantine of individuals diagnosed with the SARS-
CoV-2 virus along with their family members will be effective in reducing cases.
11.17.5 Lack of Resources for Implementing Public

Health and Social Measures (Br-5)
Insufficient funds, improper resource allocation, short-ranged mentality, lack of interest,
etc., constitute the lack of resources. Lack of resources complicates setting up isolation
wards or treatment centers for coronavirus and providing critical care to those suffering
from the most severe cases of COVID-19. An increase in the number of COVID-19-infected
cases might put significant pressure on hospitals related to critical care facilities, some of
which may not have proper resources or manpower to cope with this situation. This bar-
rier includes resources such as equipment, personnel, and financial dealings, which are
considered to be critical barriers while implementing COVID-19 preventive measures.
11.17.6 Lack of Medical Facilities at Community Level (Br-6)

The pandemic novel coronavirus disease (COVID-19) has raised the demand for medi-
cations, vaccinations, testing facilities, diagnostics, and reagents. Procurement, use, and
management of medical products must be carefully done. Shortage of medical facilities
such as personal protective equipment and medical resources (i.e., oxygen supply and ven-
tilators) have aggravated the rise of infections in Wuhan, China.
11.17.7 Lack of Door-to-Door Services During Quarantine Period (Br-7)

Around the globe, a major portion of public is under self-quarantine to prevent the
spread of novel COVID-19, facing several issues such as shortage of basic groceries.
The door-to-door services can prove a better plan in order to avoid large gatherings at
distribution centers and medical shops.
11.17.8 Lack of Proper Communication between Health

Advisors and the Public (Br-8)
Communication is a vital element in all phases of the healthcare procedure. Communication
is playing important role in patient’s care as it involves different people group of doctors,
nurses, specialists, and other staff at a hospital at different stages to share patient informa-
tion and discussing the treatment. The aspects of health care include team work; leader-
ship and workplace culture are all affected due to poor communication. Institutions with
strong communication strategies can enrich the health of their patients, while those with-
out effective procedures can adversely affect the well-being of patients. Healthcare experts
and organizations need to understand the significance of communication in healthcare
sector in order to stop the COVID-19 transmission. Also, proper communication between
health advisors and public will motivate people to be aware of COVID-19 and take ade-
quate measures to prevent its transmission.
11.17.9 Lack of Government Policies (Br-9)

It is obligatory for governments to formulate effective policies for the prevention, treat-
ment, and control of harmful diseases. Governments must ensure that the details they
share to the public about COVID-19 are accurate, timely, and consistent with human rights
principles. Also, government should frame policies that could be easily implemented to
prevent COVID-19 disease.
11.17.10 Public Stigmatization (Br-10)

Stigma arises when people adversely link a particular group with an infectious disorder,
such as COVID-19. Stigma can drive people to hide their illness, which prevents patients
from seeking immediate health care and discourages them from following health mea-
sures. Stigmatization may progressively contribute to more severe health issues, continu-
ous transmission, and difficulty in managing infectious diseases during an outbreak.
11.18 Responsibilities of Health Professionals, Bureaucrats,

and Elected Members of Parliament to Control the
Pandemic under Constitutional Framework
The physicians, especially those engaged in public health work, should enlighten the pub-
lic concerning quarantine regulations and measures for the prevention of epidemic and
communicable diseases. At all times, the physician should notify the constituted public
health authorities of every case of communicable disease under his/her care, in accor-
dance with the laws, rules, and regulations of the health authorities. The physicians have a
moral duty to treat, but they do have the same human rights as all citizens and need to be
protected against infectious diseases. The hospitals, professional regulatory bodies, and
governments must ensure and provide the necessary resources to protect the staff car-
ing for the infected patients, not just PPE, but also training, environmental controls, and
policies and procedures to prevent the spread. A balance of efficiency and innovation is a
pressing priority. It is the need of the hour to be mindful of the existing laws and our rights
and duties in the era of current pandemic. This section thus elaborates that “whenever an
epidemic occurs, a physician should not abandon his duty for the fear of contacting the
disease.” The only exception will be a situation where the physician himself has a medi-
cal condition that places him in a very high-risk category upon exposure to the contagion.
The responsible physician is expected to create awareness about the disease in the society
and work in accordance with the framework of established rules and regulations. Across
the world, states have had to play a leading role in responding to the pandemic. In the
course of this response, governments and public administrators have had to, and cho-
sen to, regulate the social and economic life of citizens to an extraordinary extent. The
COVID-19 pandemic has challenged the state in many ways. First and foremost, the con-
sequential effects of decades of differential investments in building and neglecting basic
and dynamic state capacities and public systems have been laid bare, especially when
confronted with a health crisis of this magnitude. (1) From the outset, the global pandemic
also required unprecedented coordination and collaboration at all levels of the system,
along with decentralized action on multiple fronts. Even as countries faced an urgent and
growing health crisis, the actions taken to try to control it: physical distancing, lockdowns,
prolonged physical closure of institutions, travel restrictions, etc., gave rise themselves to
extraordinary levels of economic and social distress that continue to be difficult to ade-
quately measure or fully comprehend. And in a situation where the failure of some to
adhere to behavioral norms and conduct required of all could place the entire collective at
risk, the state acquired an expanded role in constantly framing and ensuring adherence to
myriad, unusual rules that regulated the behavior of citizens and the full spectrum of pub-
lic and private institutions over an undefined period of time. As a consequence, across the
world, the pandemic placed new pressures and diverse demands on public sector work-
ers, from frontline functionaries to central administrators, most of whom were deployed
in crisis management in addition to adapting to rapidly changing work environments for
what would be routine processes in ordinary times. (2) Given the structures of governance
and administration in India, the members of the Indian Administrative Service (IAS), the
permanent, higher civil service, played a vital role in the country’s COVID-19 response.
They were prominent members of the multiple empowered action groups constituted at
the center in New Delhi; participated in specially appointed teams tasked with leading the
COVID-19 response in different states; and occupied pivotal roles in leading field admin-
istration in the districts. These roles were constantly highlighted and scrutinized in the
media, ranging from features lauding the achievements of district collectors and editorials
lambasting the bureaucracy for compulsively issuing confusing administrative orders, at
one time amounting to over 4,000 executive orders in 4 months. This report presents and
discusses the key findings of a survey of IAS officers in the context of the COVID-19 crisis
and response in India. Unlike some other national civil services, India does not have a
tradition of conducting regular surveys of its bureaucracy. Major national civil services
survey conducted in 2010 and more recent studies on the IAS focus on the challenges of
administrative reforms. We hope that this survey on the pandemic and public adminis-
tration is both a related and distinctive contribution to our understanding of the Indian
bureaucracy. It is the first of a series of studies that seek to engage with an ongoing and
renewed deliberation on the past, present, and future of public administration and state
capacity in India. Indian federalism rests on three pillars: a strong center, cooperative fed-
eralism, and flexibility. These characteristics have now assumed a pivotal role in India’s
handling of the COVID-19 pandemic, which demands a quick and efficient response from
the central (or Union) and state governments. As with many other jurisdictions across
the world, India’s response to the COVID-19 pandemic has involved either “lockdowns”
or complete cessation of activities deemed “non-essential”—right across the country. In

India, such lockdowns (and their governing regulations) have been characterized by a
concentration of power in the central government. The Ministry of Home Affairs, and not
state governments, is prescribing the duration and regulation of several lockdowns. This is
unlike other federal jurisdictions such as the USA or Canada, where states and provinces
are determining the conditions of their lockdowns. As India enters its fourth iteration of
central government-imposed lockdowns and looks toward reopening the economy, the
constitutional propriety of such a nationwide lockdown becomes questionable is the cen-
tral government usurping powers not vested in it.
11.18.1 The Legal Framework for Combating a Pandemic in India

The Seventh Schedule of the Indian Constitution divides powers between the Union and
state governments. This schedule contains three lists, each with an inventory of the rel-
evant domain of jurisdiction: the Union List (the Union’s exclusive domain), the State List
(the states’ exclusive domain), and the Concurrent List (areas over which both levels of
government can legislate). The constitutional architecture shows that when it comes to
tackling the COVID-19 pandemic, the central government is far from being the singular
source of governance. In fact, the State List (List II) contains the subjects of public order
and public health and the Concurrent List (List III) includes the aspect of prevention of
inter-state transmission of infectious diseases. The other relevant piece of legislation is
the Epidemic Diseases Act, passed in 1897 to tackle the spread of the plague in India.
The Epidemic Diseases Act confers powers on the state governments to enact regulations
necessary to address the outbreak of any dangerous epidemic. However, it bestows only
limited powers, restricted to the regulation and inspection of ships and vessels, upon the
central government (Figure 11.4).
The central government’s authority to impose these lockdowns unilaterally, however,
purports to emanate from Sections 6(2) and 10(2)(l) of the Disaster Management Act (as
can be seen from several Ministry of Home Affairs notifications). These provisions make
allowance for the establishment of a “National Executive Committee,” which can, in turn,
develop guidelines or directions for the handling of the response to a given disaster. As
these guidelines are binding on both the central and state governments, they effectively
allow the central government to consolidate its power through the issuance of guidelines
during a “disaster.” While the Seventh Schedule does not contain an entry on “disaster man-
agement,” Article 248 of the Constitution read with Entry 97 of the Union List (List I) of the
Seventh Schedule confers residuary powers upon the central government. Consequently,
the central government has the power to legislate over disaster management and issue
executive guidelines pursuant to such power. This cannot, however, impinge upon pow-
ers the Constitution confers upon the state governments. A perusal of the constitutional
scheme suggests that state governments are solely responsible for pandemic control within
their state and the central government must provide assistance on a macro-scale, to pre-
vent inter-state transmission of the disease. In contrast, the central government’s COVID-
19-related notifications reveal an encroachment on state government powers. For example,
the guidelines accompanying the declaration of the first lockdown in India dated March
24, 2020, make regulations related to, inter alia, hospitals (explicitly covered by Entry 6 on
the State List), markets (expressly included in Entry 52 on the State List), and state govern-
ment offices (covered by “State Public Offices” Entry 41 on the State List). Similar encroach-
ments may be found in subsequent guidelines issued along with subsequent extensions
of the lockdown. In accordance with Articles 73 and 162 of the Constitution, the executive
•Can be delegated
involve organizational •Cannot be
goals and may or delegated
may not have
involve Personal
personal
implications goals
Organizational Personal
Decisions decisions
Basic Routine
decisions Decisions
•Unique involve long

term commitments •Repetitive involve
involve large health short term
related investments
commitments involve
pandemic crisis are
usually serious
small investments
attention consequences are
usually trivial
FIGURE 11.4
National Health Policy decisions chart for COVID-19 pandemic crisis.
powers of the central and state government are coextensive with their legislative pow-
ers. The central government’s guidelines, therefore, invaded aspects of governance that
fall within the exclusive domain of the state governments. Moreover, the Constitution of
India does provide a mechanism for the central government to legislate (and consequently
regulate) matters covered by the State List, allowing for flexibility when matters extend
beyond the purview of the state governments. Article 249 of the Constitution permits the
central government to legislate on subjects contained in the State List as long as it is in the
national interest. One could argue that responding to an unprecedented outbreak of a pan-
demic is a matter of national interest. However, to do so, the Council of States must pass a
resolution, finding it is necessary, or expedient in the national interest, that the Parliament
ought to legislate on a matter enumerated in the State List. Such a resolution must receive
the support of at least two-thirds of the members present and voting. In this instance,
there does not appear to be a resolution allowing the central government to act in the
manner in which it is. The constitutional propriety of the central government’s response
to the COVID-19 pandemic is questionable, which begs the question of why there has been
a lack of protest from the states. But acquiescence is characteristic of Indian federalism,
which relies on having a strong center and subordinate states. In Union of India vs State of
Rajasthan, Indian federalism was described as “watered down.” In State of West Bengal vs
Union of India, the Supreme Court described Indian federalism as being where “the politi-
cal sovereignty is distributed between… the Union of India and the States with greater
FIGURE 11.5
Determinants of National Health Policy—rationality model.
Weightage in favour of the Union.” This is very unlike the American notion of federalism.
The lack of protest against the central government’s encroachment upon state powers may
be attributable to this conventional understanding of the subordinate role of states within
the India (Figure 11.5).
11.19 Indian Health Policy—Conclusions

India’s response to the COVID-19 pandemic highlights a grim reality of Indian federalism.
The absence of a declaration of “emergency” under the Constitution does not prevent the
central government from consolidating power within itself. The lack of demurrer from
the state governments in such times is not a function of cooperative federalism or the flex-
ibility of Indian federalism, but detrimental passivism in times in which governmental
accountability is paramount. While one might argue that tackling the outbreak of COVID-
19 is of national importance, and accordingly requires the center to act authoritatively,
any response to such novel situations must not impinge on the constitutional rights of the
states in the absence of their consent.
Akshay Aurora is a lawyer practicing at the High Court of Judicature, Bombay, India
(Aurora, 2020).
11.20 International Health Policy

According to the World Health Organization, preventive measures by individuals and
communities and other non-pharmaceutical measures (i.e., handwashing; surface clean-
ing; isolation of sick individuals; and closure of schools, working spaces, and social venues)
remain the most powerful tools against the spread of the virus until a vaccine or treatment
is discovered, which could take many months.
But how do you wash your hands when you don’t have access to clean water?
How do you stay away from people when you live in an overcrowded refugee camp?
How do you not leave your home when you are the sole breadwinner of an entire family
and working from home is not even a concept where you live?
How do you apply confinement measures when your life depends on running away?
These are the questions for over 168 million people worldwide.
On top of this, the short- and long-term social and economic impacts of these measures
are significant, even for high-income countries. We are already seeing the damage inflicted
on incomes and economic growth across the globe. In lower-income settings, this could be
considerably worse.
11.21 Redefining the “High-risk” Group

We know that the COVID-19 virus can infect anyone and that some groups are at higher
risk of severe illness or death (people over 70 years and those with underlying health con-
ditions). In lower-income countries, although there is a lower life expectancy, underlying
health conditions and comorbidities tend to be very common in the whole population,
including children.
In many countries of Africa, Asia, and other regions of the world, endemic malnutri-
tion, high prevalence of infectious diseases, and increasing non-communicable diseases
may completely change the risk profile of the populations. Weak health systems, political
instability, high numbers of refugees and internally displaced people, and a lack of social
protection are additional factors that further compromise the chances of these regions cop-
ing with and recovering quickly from COVID-19.
Maintaining life-saving health programs is, therefore, more crucial than ever to support
vulnerable populations. However, it is also more difficult to keep operations running in
these circumstances.
11.22 A Challenging Time to Deliver, but the Worst Moment to Stop

Many countries have closed their borders and restricted travel, making it extremely
difficult to deploy staff or supplies where they are needed the most. Strict movement
restrictions within countries also affect our program staff on the ground. The crucial
work to strengthen health systems could be seriously impacted, weakening the ability
of health workers to provide routine services to the general population and to respond
to the pandemic. The impact on water, sanitation, and hygiene programs along with
other health promotion activities may also increase the rate COVID-19 spreads among
the population. If programs that support people’s livelihoods are impacted, it could put
their food supply at risk. Labor shortages, transport disruption, and quarantine mea-
sures could also affect staple food production and availability, as was the case during
the Ebola crisis in 2014, but this time on a much bigger scale. Moreover, with schools
closed, the most vulnerable children are now potentially deprived of their only guar-
antee of a decent meal for the day. The challenge is certainly vast and complex, but not
insurmountable. While we respond to this new emergency, it is clear that we must also
continue to deliver existing life-saving programs and ensure no resources are diverted
from current operations.
11.23 WHO Policy during the Pandemic Crisis

The COVID-19 pandemic is straining health systems worldwide. The rapidly increasing
demand for health facilities and healthcare workers threatens to leave some health systems
overstretched and unable to operate effectively. Previous outbreaks have demonstrated
that when health systems are overwhelmed, mortality from vaccine-preventable and other
treatable conditions can also increase dramatically. During the 2014–2015 Ebola outbreak,
the increased number of deaths caused by measles, malaria, HIV/AIDS, and tuberculosis
attributable to health system failures exceeded the deaths from Ebola. “The best defence
against any outbreak is a strong health system,” stressed WHO Director-General Tedros
Adhanom Ghebreyesus. The COVID-19 is revealing how fragile many of the world’s health
systems and services are, forcing countries to make difficult choices on how to best-meet
the needs.
To help countries navigate through these challenges, the World Health Organization
(WHO) has updated operational planning guidelines in balancing the demands of
responding directly to COVID-19 while maintaining essential health services delivery
and mitigating the risk of system collapse. This includes a set of targeted immediate
actions that countries should consider at the national, regional, and local levels to reor-
ganize and maintain access to high-quality essential health services for all. Countries
should identify essential services that will be prioritized in their efforts to maintain con-
tinuity of service delivery and make strategic shifts to ensure that increasingly limited
resources provide maximum benefit for the population. They also need to comply with
the highest standard in precautions, especially in hygiene practices, and the provision
of adequate supplies, including personal protective equipment. This requires robust
planning and coordinated actions between governments and health facilities and their
managers. Some examples of essential services include routine vaccination; reproduc-
tive health services, including care during pregnancy and childbirth; care of young
infants and older adults; management of mental health conditions as well as commu-
nicable diseases and infectious diseases such as HIV, malaria, and TB; critical inpatient
therapies; management of emergency health conditions; and auxiliary services such as
basic diagnostic imaging, laboratory services, and blood bank services, among others.
Well-organized and prepared health systems can continue to provide equitable access
to essential services delivery throughout an emergency, limiting direct mortality and
avoiding increased indirect mortality. The guidelines stress the importance of keeping
up-to-date information. This requires frequent transparent communications with the
public and strong community engagements so that the public can maintain trust in the
system to safely meet their essential needs and to control infection risk in health facili-
ties. This will help ensure that people continue to seek care when appropriate and adhere
to public health advice.
11.24 Take-Home Message
The scenes of suffering in India are hard to comprehend. More than 20.2 million cases
of COVID-19 had been reported, with a rolling average of 378,000 cases a day, together
with more than 222,000 deaths, which experts believe are likely to be substantial under-
estimates. Hospitals are overwhelmed, and health workers are exhausted and becom-
ing infected. Social media are full of desperate people (doctors and the public) seeking
medical oxygen, hospital beds, and other necessities. Yet before the second wave of cases
of COVID-19 began to mount in early March 2021, the Indian Minister of Health Harsh
Vardhan declared that India was in the “endgame” of the epidemic. The impression from
the government was that India had beaten COVID-19 after several months of low case
counts, despite repeated warnings of the dangers of a second wave and the emergence of
new strains. Modeling suggested falsely that India had reached herd immunity, encourag-
ing complacency and insufficient preparation, but a serosurvey by the Indian Council of
Medical Research in January 2021 suggested that only 21% of the population had antibodies
against SARS-CoV-2. Despite warnings about the risks of superspreading events, the gov-
ernment allowed religious festivals to go ahead, drawing millions of people from around
the country, along with huge political rallies conspicuous for their lack of COVID-19 miti-
gation measures. The message that COVID-19 was essentially over also slowed the start of
India’s COVID-19 vaccination campaign, which has vaccinated less than 2% of the popula-
tion. At the federal level, India’s vaccination plan soon fell apart. The government abruptly
shifted course without discussing the change in policy with states, expanding vaccination
to everyone older than 18 years, draining supplies, and creating mass confusion and a mar-
ket for vaccine doses in which states and hospital systems competed. The crisis has not
been equally distributed, with states such as Uttar Pradesh and Maharashtra unprepared
for the sudden spike in cases, quickly running out of medical oxygen, hospital space, and
the capacity of cremation sites, and with some state governments threatening those ask-
ing for oxygen or a hospital bed with national security laws. Others, such as Kerala and
Odisha, were better prepared and have been able to produce enough medical oxygen in the
second wave to export it to other states. India must now pursue a two-pronged strategy.
First, the botched vaccination campaign must be rationalized and implemented with all
due speed. There are two immediate bottlenecks to overcome: increasing vaccine supply
(some of which should come from abroad) and setting up a distribution campaign that
can cover not just urban, but also rural and poorer citizens, who constitute more than 65%
of the population (over 800 million people), but face a desperate scarcity of public health
and primary care facilities. The government must work with local and primary healthcare
centers that know their communities and create an equitable distribution system for the
vaccine. Second, India must reduce SARS-CoV-2 transmission as much as possible while
the vaccine is rolled out. As cases continue to mount, the government must publish accu-
rate data in a timely manner and forthrightly explain to the public what is happening and
what is needed to bend the epidemic curve, including the possibility of a new federal lock-
down. Genome sequencing needs to be expanded to better track, understand, and control
emerging and more transmissible SARS-CoV-2 variants. Local governments have begun
taking disease containment measures, but the federal government has an essential role in
explaining to the public the necessity of masking, social distancing, halting mass gather-
ings, voluntary quarantine, and testing. Modi’s actions in attempting to stifle criticism and
open discussion during the crisis are inexcusable. The Institute for Health Metrics and
Evaluation estimated that India would see a staggering 1.5-2.0 millions (projected deaths)
from COVID-19 by August 1, 2021. If the outcome of the spreading of SARS–Cov-2 is deeply
rooted at the community level, the Indian national government would be responsible for
presiding over a self-inflicted national catastrophe. India squandered its early successes
in controlling COVID-19. As of April 2021, the government’s COVID-19 taskforce had not
met in months. The consequences of that decision are clear before us, and India must now
restructure its response while the crisis rages. The success of that effort will depend on the
government owning up to its mistakes, providing responsible leadership and transpar-
ency, and implementing a public health response that has science at its heart.
11.25 Conclusions
The coronavirus disease continues to spread across the world following a trajectory that
is difficult to predict. The health, humanitarian, and socioeconomic policies adopted by
countries will determine the speed and strength of the recovery. The ILO’s four-pillar
policy framework presented in this brief provides guidance not only for countries as they
progress through the various phases of the crisis, but also for the international community
as a whole. There must be a global human-centered response that is grounded in solidar-
ity. International labour standards (ILS) contain guidance for ensuring decent work that
is applicable even in the unparalleled context of the COVID-19 crisis. In particular, the
Employment and Decent Work for Peace and Resilience Recommendation, 2017 (No. 205),
emphasizes that crisis responses need to “ensure respect for all human rights and the
rule of law, including respect for fundamental principles and rights at work and for inter-
national labor standards.” The standards dealing with safety and health at work, social
security, employment, non-discrimination, working arrangements, and the protection of
specific categories of workers provide guidance on the design of rapid responses that can
facilitate a stronger recovery from the crisis. A coordinated global effort is required to
support countries that currently do not have sufficient fiscal space to finance social policy,
in particular universal social protection systems. Debt sustainability should be priori-
tized in this endeavor. Without long-term structural changes; the deep-rooted inequalities
exposed by the crisis will merely intensify. As well as tackling the immediate effects of the
crisis, the international community now has a unique opportunity to adopt policies aimed
at achieving social justice and a human-cantered future of work.
a. Improve international emergency response coordination.
b. Combat antimicrobial resistance.
c. Build public health capacity in low- and middle-income countries.
d. Envision the next generation of President’s Emergency Plan for AIDS Relief
(PEPFAR).
e. Confront the threat of tuberculosis.
f. Sustain progress toward malaria elimination.
g. Improve survival in women and children.

h. Ensure healthy and productive lives for women and children.
i. Promote cardiovascular health and prevent cancer.
j. Accelerate the development of medical products.
k. Improve digital health infrastructure.
l. Transition investments toward global public goods.
m. Optimize resources through smart financing.
n. Commit to continued global health leadership.
References
Agurto I. et al., Improving cervical cancer prevention in a developing country. Int J Qual Health Care
2006; 18: 81–86.
Agyepong I.A., Adjer S. Public social policy development and implementation: A case study of the
Ghana National Health Insurance scheme. Health Policy Plan 2007; 23(2): 150–160.
Aurora A. The constitutional propriety of India’s COVID-19 response from a distribution of powers per-
spective. IACL-AIDC Blog. 2 June 2020. https://blog-iacl-aidc.org/2020-posts/2020/6/2/the-
constitutional-propriety-of-indias-covid-19-response-from-a-distribution-of-powers-perspec-
tive.
Basavarajaiah D.M., Narasimha Murthy B. Ethical perspective of medical research. In: Design of
Experiments and Advanced Statistical Techniques in Clinical Research. Singapore: Springer Nature,
2020: 333–345.
Carter M., Shieh J. Molecular cloning and recombinant DNA technology. In: Carter M., Shieh J. (eds.)
Guide to Research Techniques in Neuroscience, Second edn. Cambridge, MA: Academic Press,
2015: 219–237. doi: 10.1016/B978-0-12-800511-8.00010-1.
Chen N., Zhou M., Dong X., et al. Epidemiological and clinical characteristics of 99 cases of 2019
novel coronavirus pneumonia in Wuhan, China: A descriptive study. Lancet 2020; 395: 507–513.
doi: 10.1016/S0140-6736(20)30211-7.
Ciliska D., et al. Diffusion and dissemination of evidence based dietary strategies for the prevention
of cancer. Nutr J, 2005; 4(13): 25–28
Cohen A. Organizational commitment and turnover: A meta-analysis. Acad Manag J 1993; 36(1):
1140–1157.
Coiera E. Communication systems in healthcare. Clin Biochem Rev 2006; 27(2): 89–98.
Collins T. Health policy analysis: A simple tool for policy makers. Public Health 2005; 119: 192–196.
Cousens S., Blencowe H., Stanton C., Chou D., Ahmed S., Steinhardt L., Creanga A.A., Tunçalp O.,
Balsara Z.P., Gupta S., Say L., Lawn J.E. National, regional, and worldwide estimates of still-
birth rates in 2009 with trends since 1995: a systematic analysis. Lancet, 2011, Apr 16; 377(9774):
1319–1330.
Edward A., et al. Configuring balanced scorecards for measuring health system performance:
Evidence from 5 years evaluation in Afghanistan. PLoS Med 2011; 8: 1001066.
Faden R.R., et al. An ethics framework for a learning health care system: A departure from traditional
research ethics and clinical ethics. Hastings Cent Rep 2013; 1(2): 16–27.
Fan V.Y., Mahal A., et al., Learning and getting better: Rigorous evaluation of health policy in India.
Nat Med J India 2014; 24(1): 325–327.
Guldenmund F.W. The nature of safety culture: A review of theory and research. Safety Sci 2000; 34(3):
215–257.
Hadaya J., Schumm M., Livingston E.H. Testing individuals for coronavirus disease 2019 (Covid-19).
J Am Med Assoc 2020; 323: 1981. doi:10.1001/jama.2020.5388.
Hansen P.M., et al. Measuring and managing progress in the establishment of basic health services:
The Afghanistan health sector balanced scorecard. Int J Health Plan Manag 2008; 23: 107–117.
Lam A. Tacit knowledge, organizational learning and societal institutions: An integrated framework.
Organ Stud 2000; 21(3): 487–513.
Lu H., Stratton C.W., Tang Y.W. Outbreak of pneumonia of unknown etiology in Wuhan, China: The
mystery and the miracle. J Med Virol 2020; 92(4): 40–41. doi: 10.1002/jmv.25678.
Mandala J., et al. Prevention of mother-to-child transmission of HIV in Zambia: Implementing effica-
cious ARV regimens in primary health centers. BMC Public Health 2009; 9: 314–315.
MoHFW report, January 2022 www.mohfw.gov.in.
North D.C. 1990. Institutions, Institutional Change and Economic Performance. Cambridge: Cambridge
University Press, vol. 5, pp. 30–32.
Patton C.V., Sawicki D.S. Basic method of policy analysis and planning. Vincent Navarro. What is
national health policy. Int J Health Serv 2016; 37(1): 1–14.
Peabody J.W., Rahman M.O., Gertler P.J., Mann J., Farley D.O., et al. 1990. Policy and Health Implications
for Development in Asia. Cambridge: Cambridge University Press, vol. 8, pp. 34–35.
Peters D.H., et al. A balanced scorecard for health services in Afghanistan. Bull World Health Organ
2007; 85: 146–151.
Remme J.H.F., et al. Defining research to improve health systems. PLoS Med 2010; 7(11): 58–56.
Remuzzi A., Remuzzi G. Covid-19 and Italy: What next. Lancet 2020; 395(10231): 1225–1228. doi:
10.1016/S0140-6736(20)30627-9.
Thaddeus S.D. Maine too far to walk: Maternal mortality in context. Soc Sci Med 1994; 38(8): 1091–1110.
Waddington C.J. A price to pay, part 2: the impact of user charges in the Volta region of Ghana. Int J
Health Plan Manag 1990; 5(4): 287–312.
Walt G., Schneider H., Murray S.F., Brugha R., et al. Doing health policy analysis methodological and
conceptual reflections and challenges. Health Policy Plann 2008; 23: 308–317.
WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division. Trends in
Maternal Mortality: 2000 to 2017. Geneva: World Health Organization; 2019.
World Health Organization. Weekly epidemiological update on COVID-19 - 15 March 2022. 2022.
https://www.who.int/publications/m/item/weekly-epidemiological-update-on-covid-19---
15-march-2022.
Yazdani A., Wells R. Barriers for implementation of successful change to prevent musculoskeletal
disorders and how to systematically address them. Appl Ergon 2018; 73(1): 122–132.
12
Statistical Ethics for Computational
Biology and Medical Science
12.1 Introduction
Statistics is a branch of science that deals with the formulation of new theoretical and
applied postulates. It is considered as a new horizon of science to address the realistic prob-
lems of biology, medicine, agriculture, and allied sciences. Computational biology applied
to medical sciences is one of the fastest growing sectors, wherein advanced techniques
of statistical tools are being used by scientists in every experimental design. Such novel
techniques are complementary for the existing situation to explore the different theoreti-
cal and applied postulates in testing the hypothetical statement about the population- and
sample-based studies. Recent statistical tools will help researchers in the formulation of
treatment of both infectious and non-infectious diseases not limiting to COVID-19, CVD,
cancer, HIV, and associated illnesses (Altman, 1994; Goodman et al., 2002). Appropriate
tools are used to extrapolate mathematical and statistical simulations, and such simula-
tion techniques are useful for the identification of risk factors at an early stage of disease
intervention. Moreover, the development of statistical methodologies is required to address
the various questions arising from electronic maintenance of health records. By using elec-
tronic health and patient records, biostatistics experts will formulate data-driven predictive
modeling techniques to measure the extent of disease and treatment modalities of exposed
population, and so the analyzed data will strengthen physicians to draw clinical decisions
at an early stage of infection (Jensen et al., 2012; Guillemin and Gillam, 2004; Fossey et al.,
2002). The data-driven model is used for assessing the effectiveness of a particular drug
administered at a given period; it also plays a major role in research in evidence-based
cancer therapy and identification of rare genes from artificial intelligence techniques. It also
helps in complex data analysis with respect to various parameters and clinical attributes.
In-depth knowledge will be required for the researchers for effective interpretation of the
resultant findings and hypothesis testing. A reliable statistical method provides effective
conclusions, garnishing our numerical data sets and upholding the conceptual founda-
tions of applied and fundamental science for the development of conceptual theory and
quantitative reasoning to extract the information intelligently from the ocean of data sets
(Colvin, 1992; Easterbrook et al., 1991). Statistical methods and analyses are often used to
communicate research findings and to support hypotheses and give credibility to research
methodology and conclusions. Advanced statistical tools are important for researchers and
also healthcare professionals for assessing the patients to understand statistics so that they
can be informed, to evaluate the credibility and usefulness of information and to make
appropriate decisions. Unfortunately, many scientists are not adopting statistical ethics in
DOI: 10.1201/9781003204794-12 335

their research work; plausibly, this kind of deviation would affect the experimental objec-
tives and testing of hypothesis. Statistical ethics play a vital role in data collection, analy-
sis, interpretation, explanation, and presentation of a researcher. The use of statistics in an
ethical manner should guide the researchers in so many ways, for example formulation of
research for proper characterization, summarization, presentation, and interpretation of
results. Statistical ethics will provide a platform for research at all stages of experiments,
such as how to conduct the research, whether to consider a sample or the whole population,
the techniques to use in data collection and observation, and how to interpret the result part
effectively for research paper publication in peer-reviewed journals (Figure 12.1).
Scientifically, research ethics are formulated using a set of principles about how
researchers and institution, organization, and university setups should conduct them-
selves when dealing with research conducted at micro-, macro-, and human intervention
trials. Particularly relevant to the biological research, ethics are associated with selection
of sample, formulation of research design, data collection, analysis, and interpretation.
In case of social science, ethics is associated with projects involving human participants,
including surveys, focus groups, and uses of secondary data sets (Figure 12.2).
There are several ethical issues that must be considered when designing a research that
will utilize participants who are human beings (Figure 12.3) (American Psychological
Association, 2010). Unfair discrimination: In their work-related activities, psychologists
do not engage in unfair discrimination based on age, gender, gender identity, race, ethnic-
ity, culture, national origin, religion, sexual orientation, disability, socioeconomic status,
or any basis proscribed by law. Sexual harassment: Psychologists do not engage in sexual
harassment. Sexual harassment is sexual solicitation, physical advances, or verbal or non-
verbal conduct that is sexual in nature, that occurs in connection with the psychologist’s
activities or roles as a psychologist, and that either (i) is unwelcome, is offensive, or cre-
ates a hostile workplace or educational environment, and the psychologist knows or has
told this, or (ii) is sufficiently severe or intense to be abusive to a reasonable person in
Experiments -
Control the Research
variation, diagnose data
the problems
Solve the numerical

Knowledge
problems by using
predictive modeling Interpret practical and
statistical significance
techniques
Understanding-
Make scientifically
sound decisions
and communicate
them
FIGURE 12.1
Flagship of statistical approach for research data.
Statistical Ethics 337
FIGURE 12.2
Biological research new insight research hypothesis based on research ethics.
the context. Sexual harassment can consist of a single intense or severe act or of multiple
persistent or pervasive acts. Other harassment: Psychologists do not knowingly engage
in a behavior that is harassing or demeaning to persons with whom they interact in their
work based on factors such as those persons’ age, gender, gender identity, race, ethnicity,
culture, national origin, religion, sexual orientation, disability, language, or socioeconomic
status. Avoiding harm: Psychologists should take reasonable steps to avoid harming their
clients/patients, students, supervisees, research participants, organizational clients, and
others with whom they work, and to minimize harm where it is foreseeable and unavoid-
able. Multiple relationships: A multiple relationship occurs when a psychologist is in a
professional role with a person and (i) at the same time is in another role with the same
person, (ii) at the same time is in a relationship with a person closely associated with or
related to the person with whom the psychologist has the professional relationship, or
(iii) promises to enter into another relationship in the future with the person or a person
closely associated with or related to the person. A psychologist refrains from entering
into a multiple relationship if the multiple relationships could reasonably be expected to
impair the psychologist’s objectivity, competence, or effectiveness in performing his/her
functions as a psychologist, or otherwise risks exploitation or harm to the person with
whom the professional relationship exists. Multiple relationships that would not reason-
ably be expected to cause impairment or risk exploitation or harm are not unethical.
12.1.1 Importance of Research Ethics
1. To understand and follow healthcare laws.

2. To understand the moral structure of our actions both ethically and legally.
3. To understand and appreciate the differences in moral reasoning among individuals
and groups of individuals.
FIGURE 12.3
Flowchart of research ethics.
4. To understand and learn from bioethical dilemmas that clients face.

5. To understand our own values, morals, and ethical stances.
6. To understand the need to confront biases and bigotry.
Research misconduct is triggered by the lack of personnel and professional integrity, pres-
sure in the working environment, the peril of publish or perish and failure to sanction
and misconduct (Figure 12.4). Predatory publishing disseminates false information to the
scientific community. The process model involves charging publication fees to authors
without providing peer review.
12.1.2 How to Recognize Predatory Journals
1. Superficial peer review or there is no peer review process.

2. No editorial board.
3. Missing affiliation information.
FIGURE 12.4
Issues and challenges that arises due to misconduct of research.
4. Lack of transparency in publishing operation.

5. Information about author fees is not disclosed.
6. Boastful language for author.
7. False claims about impact factors and indexing agency.
8. Spam e-mail sent to author e-mail.
9. Spam request to author.
10. Inconsistent publication policy and license for common attributes.
11. Minimal or no copywriting or proofreading for submission.
12.2 Statistical Ethics
Since ethical issues play a major role in medical and biological research, as researchers of
institutions that produce or use statistics, we have to explore the ethical issues that arise in
statistics in general and applied research in particular. Below is the list of some parameters
which might mislead the statistical science; although not exhaustive, ethical consideration
do arise in research studies. If you consider in-depth practical knowledge, in many ways,
the researchers mislead the statistics at the time of inception of experimentation or research,
selection of study population, framing of hypothesis, wrong intervention of methodology,
data falsifiability, deliberate fraudulent behavior by the researcher, use of incorrect procedure,
omitting data which do not support a researcher’s ideas, wrong use of statistics in the analysis
and interpretation phase, and also guidance of the researcher by persons other than statistical
experts. The researchers should strictly adhere to the following ethical considerations.
12.2.1 Honesty
To strive for honesty in reporting data, results, methods and procedures, and publication status.
12.2.2 Objectivity
To avoid bias in experimental design, data analysis, data interpretation, peer review, per-
sonnel decisions, and other aspects of research where objectivity is expected or required.
12.2.3 Integrity
To keep the promises and agreements, act with sincerity; strive for consistency of thoughts
and actions.
12.2.4 Carefulness
To avoid careless errors and negligence, one’s own and peer’s work should be carefully
and critically examined. Researchers should keep good record of research activities such
as data collection, research design, and correspondence with publishers.
12.2.5 Openness
To share research data, results, ideas, tools, and resources to the institutional library for
dissemination purpose and also to be open to criticism and new ideas.
12.3 Research Ethics in Human Interventions

Research ethics involve the application of fundamental ethical principles to a variety of
research topics taken by the researchers with respect to human intervention trials, such as
a drug trial, plasma therapy, organ transplantation, and termination of pregnancy driven
by rape victims. These include the design and implementation of research involving
human and animal experimentation, including various aspects of academic and research
scandals to deviation of regularity guidelines of research. The following ethical principles
are listed for the researchers.
12.4 Educate the Participants about Risks and Benefits

A written consent needs to be obtained before involving participants in the research and
to keep the participants informed accordingly.
12.4.1 Confidentiality
Protect the confidentiality of communications, such as research questionnaires, confiden-
tial papers with respect to the research project, and personal records and publications.
12.4.2 Responsible Publication
Publish in order to advance research and scholarship, not to advance just your own carrier.
Avoid wasteful and duplicative publication.
12.4.3 Non-Discrimination
Avoid discrimination on the basis of sex, race, ethnicity, or other factors that are not related to
their scientific competency, and also integrate to follow the basic principle of ethics. (i) Discuss
intellectual property rights. (ii) Be conscious of multiple roles. (iii) Follow the informed con-
sent rules. (iv) Respect confidentiality and privacy at all times. (v) Tap into ethical resources.
12.4.4 Human Subject Protection

When conducting research on human subjects, minimize the harm and risk factors,
while maximizing the benefits with respect to human dignity, privacy, and autonomy.
Researchers should take special precautions with vulnerable population and strive to dis-
tribute the benefits and burden of research fairly.
12.4.5 Legality
Know and obey the relevant laws of institutional and government policy intervention.
12.5 Statistical Implications for Research Study

In many research problems, either medical, social, or agricultural research study, the statisti-
cal implication is a very important factor to describe the overall research envoi. We have seen
in many research studies, findings, or inputs described in the discussion part of the thesis
that experts were asked to write about the implications of their results. While many research
scholars will often just descriptively repeat the resultant figures in numbers, chairs are look-
ing at the larger picture when it comes to research findings. As such, this is where research
implications come in. However, the most important questions to ask yourself when looking
at your findings are the following: Why is this study important? How do my findings apply
to real-world problems? What are the things that could potentially happen because of this
new formation? These are the roots of your implications. By discussing the importance of
findings within a real-world context instead of theoretical postulates or research gaps in the
review of literature context, the researchers should be demonstrating the practical, social,
and economic feasibility of any kind of research. This is what institutional or extramural
research is looking for. The implications not only details part of the practical significance
of your study, but can also provide realistic methods for addressing the problem you pre-
sented within the background of the research. Even researchers fail to solve the problem,
which often happens. Researchers are still able to talk about why their findings matter in the
larger realm of interests on the issue they addressed. If you believe that your findings would
turn out one way and previous researchers also believed the same notion, yet your findings
turned out entirely different, you have essentially created entirely new avenues for future
researchers to explore. Implications also act as a road map to sort of individuals interested in
public policy decisions, who will often apply your findings and show why they are important
to whatever cause in which they are interested. It should be noted that research implications
are not the same thing as your recommendations for the practice of future research, which
will be covered in the forthcoming edition. While those sections deal with the shortcomings
of your study, implications are based solely on the strength of the study, what we can found,
why it is important, and how we can apply it within real-world settings.
12.6 Selection of Appropriate Statistical Methods for Testing

Research Hypotheses and Research Implications
The selection of suitable or appropriate statistical method is the prime step for the analysis
of research data and testing of hypotheses on the medical, agricultural, and biological data
frames. An unrealistic selection of the statistical method creates some serious problems not
only during the interpretation of describing your research findings, but also in the conclu-
sion part. In statistical terms, for each specific situation, suitable methods are available to
analyze and interpret the data. We should select the appropriate statistical method. One
needs to know the assumptions and conditions of the statistical tools or methods so that the
proper method can be selected for data compilation. Other than the knowledge of the sta-
tistical methods, another very important aspect is the nature and type of the data collected
and the objective of the study because, statistical methods are selected based on the objec-
tives. As far as the authors’ expertise and experience in medical and veterinary and life
science discipline is concerned, the researchers think that this discipline does not require
statistical methods (example clinical science). We will describe the resultant findings by
using frequency distribution and graphical representations. This type of arbitrary assump-
tions is wrong, because your resultant data will not be tested by suitable statistical methods,
your hypothesis framework is incomplete, and also your research part is invalid. The use
of a wrong or inappropriate statistical method is a common phenomenon in the published
articles in clinical and biomedical research. The use of incorrect statistical methods can be
seen in many conditions, for example the use of unpaired t test on paired data or the use of
parametric test when the data do not follow normal distribution (normalcy of data). At pres-
ent, many statistical software packages such as SPSS, STAT, Statistica, Minitab, R, and SAS
are available, and using these, one can easily perform statistical analyses, but the selection
of appropriate statistical test is still a difficult task for biomedical and veterinary science
researchers, especially those with nonstatistical background (Figure 12.5 and Table 12.1).
12.7 Generalized Linear Model (GLM)

12.7.1 Model
Model is the theoretical postulates driven by the salient practical aspects to formulate
mathematical derivation by using real data sets. There are three types of models:
i. State mathematical model—generalized linear and nonlinear models.

ii. Dynamic model.
iii. Compartmental model.
FIGURE 12.5
Factors affecting the selection of statistical methods.
TABLE 12.1
Statistical Methods Used for Different Conditions of Data Frame
Description Parametric Non-Parametric
(i) General Method

Descriptive statistics Mean, SD, variance Median, IQR
Sample with population (or One-sample t test (n ≤ 30) One-sample Wilcoxon rank test
hypothetical value) One-sample Z test (n ≥ 30)
Two unpaired groups Independent sample t test Mann–Whitney U test/Wilcoxon
(unpaired test) rank-sum test
Two paired groups Paired t test Related samples; Wilcoxon rank test
Three or more unpaired groups One-way ANOVA Kruskal–Wallis H test
Three or more paired groups Repeated measures ANOVA Friedman test
Degree of relationship between two Karl Pearson’s correlation Spearman rank correlation coefficient
variables coefficient
Predict one outcome variable by at Linear regression model Nonlinear regression model
least one independent variable
(ii) Compare Proportion

Description Statistical method Data frame
Test the association between two Pearson chi-square test/Fisher’s Variable has ≥2 categories
categorical variables (independent exact test
groups)
Test the change in proportion McNemar’s test/Cochran’s Q Variable has 2 categories
between 2/3 groups (paired test
groups)
Comparison between two Z test for proportion Variable has 2 categories
proportions
(Continued)

Statistical Methods Used for Different Conditions of Data Frame
Description Parametric Non-Parametric
(iii) Semi-Parametric and Non-Parametric Method

Description Statistical method Data frame
To predict the outcome variable Binary logistic regression Outcome variables (two categories,
using independent variables analysis independent variable(s); categorical ≥2
variables or continuous variables or
both)
To predict the outcome variable Multinomial logistic regression Outcome variables (≥3 categories,
using independent variables independent variable(s); categorical
≥2 variables or continuous variables
or both)
Area under cutoff values in the Receiver operating Outcome variable (2 categories), test
continuous variable characteristics curve or analysis variable: continuous
To predict survival P values of the Life table analysis Outcome variable two categories,
subjects for the given equal follow-up time: continuous variable
intervals
To compare the survival time in ≥2 Kaplan–Meier curve Outcome variable (two categories),
groups follow-up time: continuous variable, one
categorical variable
To assess the predictors influencing Cox regression model or Outcome variable (two categories),
the survival probability analysis follow-up time: continuous variable, one
categorical variable; categorical ≥2
variables or continuous variables or both
To predict the diagnostic accuracy Diagnostic accuracy (sensitivity Both variables of gold standard methods
of the test variable as compared to and specificity analysis) and the test method should be
gold standard categorical 2 × 2 contingency table
Absolute agreement between two Unweighted and weighted Between two nominal variables—
diagnostic methods kappa statistics/intraclass unweighted kappa, two ordinal variables
correlation (weighted kappa, two continuous
variables—intraclass correlation
coefficient)
Thus, for our research hypothesis convenience, the focus has been on describing the
interaction or association between two or more three categorical variables mostly via
single summary of statistics and with significance testing. The model can handle more
complicated situations and analyze the simultaneous effects of multiple variables,
including mixtures of categorical and continuous variables. The structural form of the
GLM model describes the various patterns of interactions and correlation between the
variables. The model parameters provide measures of strength of associations. The
basic prerequisites of model are point estimation, hypothesis testing, and confidence
intervals. When we formulate the model, we will always keep in our mind the fol-
lowing: the objective of the research, model structure (equations), model assumptions,
parameter estimates and interpretation, model fit (goodness-of-fit and statistics), and
model selection.
For example, if we want to build a model of GLM of risk of CVD associated with vital
parameters of CBC (SGOT, SGPT, TG, etc.), we consider the following key points.
12.7.2 Objective
Model the expected value of a continuous variable Y as a linear function of the continuous
predictors.
(
Yij ~ N µ , θ 2 )
12.7.3 Model Structure
X , E(Yij ) = a + β 0 X 0 + β1 X 1 + β 2 X 2 ….β n (12.1)
where a = the intercept ; β n = coefficients of X n; X 0 , X 1 , X 2  X n are the random state vari-

ables of CBC (SGOT, SGPT, TG, CRP, etc.); and Yij = thedependent variableof ith variable with
jth cases.
12.7.4 Model Assumptions
The dependent variable Yij is normally distributed with mean µand common variance σ 2
( )
and errors eij ~ 0, σ 2 , i.e., normalcy assumptions.
12.7.5 Parameter Estimates and Interpretation

Estimate the coefficient by using predictors β0 , β1 … βn .
12.7.6 Model Fit
Diagnose your model by using coefficient of determination, residual analysis, and F-statistic.
12.8 Model Selection
As per the model criteria, we should decide on the basis of a plethora of possible predic-
tors, i.e., which variables to be included for the result part. As per the literature, the GLMs
are a broad class of models that include linear regression, ANOVA, Poisson regression, log-
linear analysis, and multinomial distribution. Table 12.2 summarizes the GLM processes.
There are three components in the GLM model.
TABLE 12.2
Different Methods Used for Model Construction
Model Random State Criteria Systematic
Linear regression Normal Identity Continuous
ANOVA Normal Identity Categorical
ANCOVA Normal Identity Mixed
Logistic regression Binomial Logit Mixed
Log-linear Poisson Log Categorical
Poisson regression Poisson Log Mixed
Multinomial response Multinomial Generalized logit Mixed
12.8.1 Random State Components

Random state components refer to the probability distribution of the response variable
“Y”, e.g., normal distribution for “Y” in the linear regression or binomial distribution of
“Y” in the binary logistic regression. It is also called a noise model or an error compo-
nent model.
X , E (Yij ) = a + β 0 X 0 + β1 X 1 + β 2 X 2 ….β n X n + (12.2)
( )
ij ~ N µ , σ 2 , where ij = the error associated with ith row and jth column in real data sets.
12.8.2 Systematic Components
Specify the explanatory variable (X1,X2…Xn) in the model, more specifically their linear
combination in creating the so-called linear predictor, e.g., β 0 + β1 + β 2 ….β n , as we have
seen in a linear regression model or as we will see in a logistic regression.
12.8.3 Link Function η or g ( µ )
Specify the link between random and systematic components. It says how the
expected value of the response relates to the linear predictor of explanatory variables,
e.g., η = g (Yi ) = E (Yi ) for linear regression, or η = Logit ( π i ) for logistic regression.
12.8.4 Assumptions of the Model
1. The dependent variables Y1, Y2…Yn are independently distributed; i.e., all cases are
independent.
2. The dependent variable Y does not need to be normally distributed, but it typi-
cally assumes a distribution from an exponential family (e.g., binomial, Poisson,
multinomial, or normal distribution).
3. The GLM does not assume any kind of linear relation between X and Y. However,
the assumptions were correlated with the linear relationship between the trans-
formed response in terms of the link function and the explanatory variables;
e.g., for binary logistic regression Logit ( π i ) = β 0 X 0 + β1 X 1.
4. Explanatory or independent variable can be even the power or some other nonlin-
ear transformations of the original independent variables.
5. The term of homogeneity of σ 2 does not need to be satisfied. In fact, it is not even
possible in many cases given the model structure, and over-scatterdness distribu-
tion may be present.
6. The error component needs to be independent, but not normally distributed.
7. GLM uses MLE rather than OLS to estimate the parameters and thus relies on
large sample approximations.
8. The goodness-of-fit measures rely on sufficiently large samples, where a heuristic
that is not >20% of the expected cell counts is <5.
12.9 Model Diagnosis Test

After the construction of the model, we should cross-check the model accuracy and robust-
ness by using various methods of statistical interpretations. Usually, we can test the model
by using the dissimilarity index.
For a table of any dimension, it equals
D=
∑ 
n −µ
i
i i
(12.3)
2n
D=
∑ n − µ =
i
i i 55.36
= 8.70% of the observations of the sample to achieve a perfect fit
2n 2 * 315
of the model.
The dissimilarity index lies between 0 ≤ D ≤ 1,where D = the proportion of sample cases
that need to move to a different cell to have the model fit perfectly.
A small D means there is little difference between the fitted values and observed counts;
a large D signifies the larger differences between the observed cell counts. The thumb rule,
if D < 0.03, indicates non-important lack of fit.
12.10 Model Diagnosis by Information Criteria

The information criteria are very useful for model diagnosis; these are different statistics
that compare the fitted and observed values, that is the likelihoods of the models, but take
into account the complexity of the model and/or sample size. The two most commonly
used to test the diagnosis are the following:
Akaike information criterion (AIC):
AIC = −2*Log L + 2*Numberof parametrs
Bayesian information criterion:
BIC = G 2 − df * Log N = −2Log * B
where N = the total number of observations and B = the posterior odds (Table 12.3).
12.11 Bayesian Analysis
The probability of occurrence of an event when calculated based on the degree of belief
(based on prior knowledge) is called the Bayesian probability. Such events do not fall
TABLE 12.3
Difference between Frequentisitc and Bayesian analysis
Frequentist Analysis Bayesian Analysis
Data are a repeatable random sample; there is a Data are fixed, probably a few samples
frequency
No expression of beliefs (formally not present); Approach deals with belief, i.e., subjective view on
objective view on probability probability. It helps to update their beliefs in the evidence
of new data frame (thus creating posterior distribution)
Provides us with a point estimate using MLE and Provides us with a posteriori distribution with high-
least square estimates density interval with mean, mode, and median stats
Parameters are fixed and unknown Parameters are unknown, random, and described
probabilistically
Confidence interval: Over an infinite sample size Credible interval: a 95% probability that the population
taken from population, 95% of these contain the value is within the limits of the interval
true population size
Statistical hypothesis: Testing with p-value and Bayes factor considered a direct test of null and alternative
significance level is employed to deduce a solution hypotheses, yielding a measure of strength of evidence
in the decision-making process
Less computationally intensive Computationally intensive
No credibility Credible
under repetitive kind of events. For example, what is the likelihood of nCov19 in different
countries to spread? But the likelihood depends on various parameters such as degree of
transmission, speed of disease progression, and how many people could be infected in
particular time. Mathematically, BA is determined by using Bayes law or rule which is
used for determining how strongly a set of evidence support the hypothesis.
P( A) ∗ P(B/A)
P ( A/B ) = (12.4)
P(B)
P ( A/B ) is the probability of hypothesis A to take place (or, B is true) given that
evidence B happened (or, B is true). It is also termed as “posterior probability of
hypothesis A”.
P ( A ) is the probability of the hypothesis before learning about evidence B. It is also
called “prior probability of hypothesis A”.
P ( B/A ) is the likelihood that evidence B is true or happened given hypothesis A is
true.
P ( B ) is the probability of evidence B to occur irrespective of whether hypothesis A
is true or false. It is also called “the total probability” of the evidence.
Illustration: We determine the astigmatic occurrence of 20 cases in the following illustra-

tive example (Figures 12.6 and 12.7).
12.11.1 Random Error
Random error occurs when one measurement is taken and its results are not the same as
the previous one. It occurs through a hit and trial method or by change. Random errors
will arise due to various factors, viz. faulty selection of sample for experiment, inception
of research without prior designing of experiments, lack of determination of sample size
FIGURE 12.6
Illustration of Bayesian problem.
FIGURE 12.7
Problems of research without the application of suitable statistical methods for data analysis.
FIGURE 12.8
Error components in a research.
(number of cases to be included), and improper selection of study material without prior
knowledge of the statistician. Random errors can be evaluated through data analytics,
applying suitable statistical methods for data analysis. These errors cannot be eliminated
completely (Figure 12.8).
12.11.2 Systematic Error
The error occurs when there is a problem in the measurement system that affects all the
measurements in the same way. A systematic error in which scale measurements differ con-
sistently from the true values is called calibration error. It has non-zero mean. The system-
atic error includes instrumental, environmental, and observational errors. The systematic
error always affects the accuracy of experimentation.
12.11.3 Research Hypothesis Is Reliable, but Not Valid

Sometimes, we describe research hypothesis and conclusion validity. The validity of the
hypothesis refers to the degree to which the statistical tools are used for testing the null
hypothesis, which is reasonable or correct. Because the null hypothesis typically states that
a relationship between two variables does not exist, the validity of a research hypothesis
and conclusion also refers to whether a relationship exists between the selected parameters
for research. Although the validity of the research hypothesis is distinct from construct
validity and external validity, it is important distinguish conclusion validity clearly from
internal validity. The validity mainly depends upon the application of suitable statistical
methods for data analysis.
12.11.4 New Research Findings Are Unrealistic Phenomena

As per the literature, the research may be very broadly defined as systematic gathering of
data and information and their compilation and interpretation of data sets for advance-
ment of scientific knowledge in any discipline. The research will attempt to find answer to
intellectual and practical questions through applications of systematic methods (revision
of accepted theories or laws in the light of new facts or practical application of such new or
revised postulates). It is one kind of movement of knowledge from the known to unknown.
However, before embarking on the process of research techniques, it seems appropriate to
present a brief overview of the research flow. The research process consists of a series of
actions or steps necessary to effectively carry out the research and the desired sequencing
of many steps. Compilation of data sets by suitable statistical methods and interpretation
is one of the key indicators for describing new research findings. Without applying reliable
statistical methods for data analysis, the entire research information would be unrealistic
approach and disseminate wrong information to the scientific community and we should
not expect further research from the tested research.
12.12 Discussion
Statistical methods to produce findings for a study are the culmination of a long process.
This process includes constructing the study design, selecting and measuring the variables,
devising the sampling techniques and sample size determination, editing the data sets, and
determining the compilation of data sets based on the objectivity of the study (Altman,
1994). The overall quality of a research depends on the entire chain process of research
flowchart events (Angell, 1997; D’Agostino et al., 2003; Beecher, 1966). The unrealistic use
of statistics can cause serious problems in the research hypothesis and also mislead the
audience and research scholars (Behrend et al., 2011; Brown and Lilford, 2006; Button et al.,
2013; Chalmers, 1990; Cios and Moore, 2002). Without statistical methods, there would be
no research to show whether the data are in support or in disagreement with the research
hypothesis (Colvin, 1992; Danyllo et al., 2013; Dicicco et al., 2006; Easterbrook et al., 1991).
Since the burden of evidence lies in the results of statistical tests or tools, without the use
of reliable statistical tools in research, we would be buried in the knowns, more questions,
open-ended conclusions, and more data than we can handle. The absence of reliable sta-
tistical methods for testing hypotheses is unable to credit new discoveries, answer new
questions, and confidently advance with new developments (Ellis, 2007; Emanuel et al.,
2000; Ford et al., 2014; Fang et al., 2012). Statistical tests form the basis on which we can trust
what the data are saying and make sense of what the raw data sets and volumes of data are
communicating. Statistical tests provide us with means to interpret the data sets accurately
so that we can make unbiased decisions on how to proceed knowing what the data are
communicating in the aspects of decision support for testing the null hypothesis (Fossey
et al., 2002; Gallagher et al., 2003; Grunwald, 2001; Guillemin and Gillam, 2004; Herkert,
2001). It also guides the way we communicate our results, and it calls for us to define why
these methods were chosen and how we arrived at our explanation based on a series of fig-
ures and charts. Besides research study design, the statistical simulation is also a great (Joly
et al., 2016; Lo, 2015; Mishra et al., 2019; McCabe et al., 2001; McGrath et al., 2010; Minkler,
2005; Narayanan et al., 2016; Portaluppi et al., 2010) way of communicating and condensing
large data sets into digestible, bite-sized pieces of information easily understood by the
researchers (Jensen et al., 2012; Kelley et al., 2003; Kuschel, 1997; Cho et al., 2008; Goodman
et al., 2002; Joly et al., 2016). These summary statistics are helpful in providing people with
an immediate idea of the big picture and whether your conclusion is valid. The important
pitfalls are listed based on the experience of researchers we noticed in real-world research,
either in vivo, in vitro, biomedical, animal, social science, or epidemiological research. After
the completion of research intervention or experimentation, researchers are willing to take
consent of a statistician to take necessary statistical inputs for data analysis and interpreta-
tion. It is one kind of haphazard movement that is observed worldwide. In addition to that,
hiding and fabrication of data are simple to project only what anyone wants to do and not
what the actual data speak. This gives rise to suspicion and non-reliability of statistical
science (Rothman and Michels, 1994; Runeson and Host, 2009; Sweeney, 2002; Shewan and
Coats, 2010; Tenopir et al., 2011; Tracy, 2010; Tunis et al., 2003; Walsham, 2006; Williams, 2008;
Zook et al., 2017). The following need to be observed and practiced while applying statisti-
cal techniques to draw inferences: (i) The statistical analysis should be carried out relevant
to the objectives of the study and there should not be any deviation; (ii) Commitment, sin-
cerity, and honesty about data collection, validation, imputation, etc., are necessary to know
the truth; (iii) Plagiarism to favor the researcher should be avoided; (iv) Statistical tech-
niques and/or the data should not be modified to get the statistical significance; (v) Above
all, the interpretation of findings should not be based merely on statistical significance, but
on the clinical, empirical, and practical evidence; and (vi) Data should be made available in
the public domain once the results are published.
12.13 Conclusions
Statistics are no substitute for a judgment; figures will not lie, but liars will figure. The ulti-
mate proper use of statistical ethics in research must rest with integrity of the individual
researchers. All research experts should follow strict ethical consideration for conducting
research to maintain data integrity, transparency, reproducibility, and institutional and
government regularity guidelines for human and animal intervention research.
References
Altman D.G. The scandal of poor medical research: We need less research, better research, and
research done for the right reasons. Br Med J 1994; 4(308): 283–284.
Angell M. The ethics of clinical research in the third world New England. J Med 1997; 12(337): 847–849.
Beecher H.K. Ethics and clinical research. N Engl J Med 1966; 274(24): 1354–1360.
Behrend T.S., Sharek D.J., Meade A.W., et al. The viability of crowdsourcing for survey research.
Behav Res Methods 2011; 43(3): 800–813.
Brown C.A., Lilford R.J. Stepped wedge trial design: A systematic review. BMC Med Res Methodol
2006; 6 (2):153–158.
Button K.S., Ioannidis J.P.A., Mokrysz C., et al. Power failure: Why small sample size undermines the
reliability of neuroscience. Nat Rev Neurosci 2013; 14 (5): 365–376.
Chalmers I. Underreporting research is scientific misconduct. J Am Med Assoc 1990; 263(10): 1405–1408.
Cho M.K., Tobin S.L., Greely H.T., McCormick J., Boyce A., Magnus D. Research ethics consultation:
The Stanford experience. IRB 2008; 30(6): 1–6.
Cios K.J., Moore G.W. Uniqueness of medical data mining. Artif Intell Med 2002; 6(26): 1–24.
Colvin J.G. A code of ethics for research in the 3rd world. Conserv Biol 1992; 6(3): 309–311.
D’Agostino Sr. R.B., Massaro J.M., et al. Non-inferiority trials: Design concepts and issues the encoun-
ters of academic consultants in statistics. J Stat Med 2003; 22(2): 169–186.
Danyllo W.A., Alisson V.B., Alexandre N.D., Moacir L.M., Jansepetrus B.P., Oliveira R.F. Identifying
relevant users and groups in the context of credit analysis based on data from Twitter. In Cloud
and Green Computing (CGC) Third International Conference IEEE 2013; Sep 30: 587–592.
Dicicco-Bloom B., Crabtree B.F. The qualitative research interview. Med Educ 2006; 40(4): 314–332.
Easterbrook P.J., Gopalan R., Berlin J.A., Matthews D.R. Publication bias in clinical research. The
Lancet 1991; 337(8746): 867–872.
Ellis C. Telling secrets, revealing lives; Relational ethics in research with intimate others. J Qual.
Inquiry 2007; 13(1): 3–29.
Emanuel E.J., Wendler D., et al. What makes clinical research ethical. J Am Med Assoc 2000; 283(20):
2701–2711.
Fang F.C., Steen R.G., Casadevall A. Misconduct accounts for the majority of retracted scientific pub-
lications. Proc Natl Acad Sci USA 2012; 109(42): 17028–17033.
Ford H. Big data and small; Collaborations between ethnographers and data scientists. Big Data Soc
2014; 1(2):256–259.
Fossey E., Harvey C., McDermott F., et al. Understanding and evaluating qualitative research. Aust
N Z J Psychiatry 2002; 36(6): 717–732.
Gallagher T.H., Waterman A.D., Ebers A.G., et al. Patients’ and physicians, attitudes regarding the
disclosure of medical errors. J Am Med Assoc 2003; 289 (8):1001–1007.
Goodman A., Pepe A., Blocker A.W., Borgman C.L., Cranmer K., Crosas M., et al. Ten simple rules for
the care and feeding of scientific data. PLoS Comput Biol 2002; 10(4):156–165.
Grunwald A. The application of ethics to engineering and the engineers moral responsibility:
Perspectives for a research agenda. Sci Eng Ethics 2001; 7(3): 415–428.
Guillemin M., Gillam L. Ethics, reflexivity and ethically important moments in research. Qual Inq
2004; 10(2): 261–280.
Herkert J.R. Future directions in engineering ethics research: Microethics, macroethics and the role of
professional societies. Sci Eng Ethics 2001; 7(3): 403–414.
Jensen P.B., Jensen L.J., Brunak S., et al. Mining electronic health records: Towards better research
applications and clinical care. Nat Rev Genet 2012; 13(6): 395–405.
Joly Y., Dyke S.O.M., Knoppers B.M., Pastinen T. Are data sharing and privacy protection mutually
exclusive. Cell 2016; 167(5):1150–1154.
Kelley K., Clark B., Brown V., Sitzia J. Good practice in the conduct and reporting of survey research.
Int J Qual Health Care 2003; 15(3): 261–266.
Kuschel R. The necessity of ethical codes in research psychiatry today. J Yugoslav Psychiatric Assoc
1997; 2 (3): 147–174.
Lo B. Sharing clinical trial data: Maximizing benefits, minimizing risk. JAMA 2015; 313(8): 793–794.
McCabe D.L., Trevino L.K., Butterfield K. Cheating in academic institutions: A decade of research.
Ethics Behav 2001; 11(3): 219–232.
McGrath J.C., Drummond G.B., McLachlan C., et al. Guidelines for reporting experiments involving
animals: The ARRIVE guidelines. Br J Pharmacol 2010; 160(7): 1573–1576.
Minkler M. Community-based research partnerships: Challenges and opportunities. J Urban Health
2005; 82(2): 223–226.
Mishra P., Pandey C.M., Singh U., Keshri A., Sabaretnam M. Selection of appropriate Statistical
Methods for data Analysis. Ann Card Anaesth 2019; 22(3): 297–301.
Narayanan A., Huey J., Felten E.W. A precautionary approach to big data privacy. In: Gutwirth
S., Leenes R., De Hert P. (eds.) Data Protection on the Move. Dordrecht: Springer, 2016:
357–385.
Portaluppi F., Smolensky M.H., Touitou Y. Ethics and methods for biological rhythm research on
animals and human beings. Chronobiol Int 2010; 27(9): 1911–1929.
Rothman K.J., Michels K.B. The continuing unethical use of placebo controls. N Engl J Med 1994;
331(6): 394–398.
Runeson P., Host M. Guidelines for conducting and reporting case study research in software engi-
neering. Empir Softw Eng 2009; 14(2): 131–164.
Science & Justice Research Center (Collaborations Group). Experiments in collaboration: interdisci-
plinary graduate education in science and justice. PLoS Biol 2013; 11(7): 1001619.
Shewan L.G., Coats J.S. Ethics in the authorship and publishing of scientific articles. Int J Cardiol 2010;
144(1): 1–2.
Sweeney L. A model for protecting privacy-fuzziness and knowledge-based systems. Int J Uncertain
2002; 10(05): 557–570.
Tenopir C.S., Allard K., Douglass A.U., et al. Data sharing by scientists: Practices and perceptions.
PLoS One 2011; 6(6): 174–178.
Tracy S.J. Qualitative quality: Eight big-tent criteria for excellent qualitative research. Qual Inq 2010;
16(10): 837–851.
Tunis S.R., Stryer D.B., Clancy C.M. Practical clinical trials: Increasing the value of clinical research
for decision making in clinical and health policy. J Am Med Assoc 2003; 290(12): 1624–1632.
Walsham G. Doing interpretive research. Eur J Inf Syst 2006; 15(3): 320–330.
Williams J.R. The declaration of Helsinki and public health. Bull World Health Organ 2008; 86(8):
650–652.
Zook M., Barocas S., Boyd D., Crawford K., Keller E., Gangadharan S.P., et al. Ten simple rules for
responsible big data research. PLoS Comput Biol 2017; 13(3): 1005399. doi: 10.1371/journal.
pcbi.1005399.
Index
Note: Bold page numbers refer to tables and italic page numbers refer to figures.
ACF residual plot 198 asymptomatic carrier 12
active carrier 12 attenuated virus vaccine 176, 177
Acute Encephalitis Syndrome (AES) 304 auditable standard 315
ADALINE 58 Aurora, Akshay 328
adaptive invasive response 103 autocorrelation function (ACF) 290, 292
additive method 81 average model decomposition method 88, 89
administrative commitment lack 322
age adjusted relative risk (aRR) 275 “Backdrop to National Health Policy 2017—
age-specific time series 278, 278–280, 279 Situation Analyses” 309
age-specific infection, Karnataka 281, 282 backward bifurcation 26, 29
age-wise prevalence breakup 281, 281 Bailey, N. T. 48
Granger causality test 289 Barcelo J. 249
LOESS model 287 Basavarajaiah, D.M. 22, 25, 301
mortality rates 275 Bayesian analysis 347–348
output 280–290 random error 348–350
percentage need for oxygen 283 research hypothesis 350–351
projection of surge 285 systematic error 350
seasonal components 286, 287 Bayesian and frequentist approaches 219
AlexNet 58 Bayesian classifier method 220, 225–226
alignment parameters 146 Bayesian IA score 231
amplification 172 Bayesian real probability 225
analytical research gap 219 Bayesian support network decision model
Anderson, R. M. 48 267–269
ANOVA F-Table 180 Bayes stochastic vaccination mode 210–211, 212
antiretroviral (ARV) 303 Bayes theorem 220
Applied Biosystems 7500 Fast Dx Real-Time Bayes weighted regression model 221–226
PCR Instrument 163, 164 behavioral risk factors 246
Apyrase 144 best linear unbiased estimation (BLUE) 62
ARIMA forecasting model 7 binary logistic regression model. 170
additive time series, decomposition of 89, 89 Bitsouni, V. 212
average model decomposition method 87, black fungus 245
88, 89 bootstrap techniques 80
backward selection 88 broad research spectrum 310–311
exponential smoothening, data 82, 82–83, 83 Burnt Finger Poisson distribution 258, 265, 267
forecasting output 86 Byun, J. H. 51
limitations 92
model output 86 Cai, L. 48
PAF distribution 91 carefulness 340
process of 83–85, 84, 86 cascade linkage model 183
reproducibility measures 87, 89, 90 case fatality rate (CFR) 14–15, 15, 288
residual density plot 87, 87 Cauchy distribution 126, 126, 127
steps 81–82 Centers for Disease Control and Prevention
artificial intelligence (AI) method 73, 253 (CDC) 217
artificial neural network (ANN) 58 chain termination PCR method 119, 120
ASCII score 140, 141 challenges 317–318
355
356 Index
Chi, E. M. 51 pandemic control 302

Chowell, G. 25 personal stress level 111, 111
chronic carrier 12 prevention measures 92
chronic lung diseases 245 priority group 183
classification tree 228 progression, majority of cases 14
client–server model 254 psychological problems 101
Coburn, B. J. 7 real data sets 80
collaborative endeavour 310 relative risk 42
communication-driven model 254 reproductive rate 9, 23
compartmental mathematical model 7, 212 research articles published 8
conditional probabilities 220, 221 seasonal variation of 90–91
confidentiality 340 second wave 278
consultation 315 side effects, vaccination 182
convalescent carrier 12 socioeconomic impact 4
COVID-19 spread of disease 12
age-specific incidence 275 stages 83
analytical-based study interventions 72 surveillance 5
anatomical structure 10–11 transmission mechanisms 11, 15
anxiety and fear 102 (see also fear and vaccination priority order 215
anxiety levels) vaccination program,
behavioral characteristics 110, 110 Government of India 215
carriers 12, 12–13, 13 vaccine allocation scheme 182
cascade linkage model 183 vaccine and their merits 182
common symptoms 11, 11 vaccine efficacy 184
conflict of interest 74 vaccines available at global level 181
containment measures 101 vaccine trials 175
control measures 5, 5 virus outbreak 101
convalescent phase 165 WHO's advise 1
decision making 1–2 COVID deaths 217, 228
diagnostic test 96 COVID sequencing 146–147
disease-free endemic equilibrium 29, 30 COVID Worldometer 179
dysfunction of immune system 172 Cox, D. R. 51
economic crisis 5 Coxian distributed SEIR model 51
economic impact assessment 17–18, 18 Cox proportional hazards model 31, 167
epidemiological aspects 15–17, 16 cross-lagged growth model 39, 39–40
epidemiology, flowchart 34 cycle threshold (Ct) values 164
government sectors 102, 112 asymptomatic cases 170, 171–172
health crisis 1–2 elderly population 172
human livelihood 79 high threshold value 165–166
hydroxychloroquine 4 lowering of 171–172
incubation periods 11–15, 13, 14 mean value 169
infectious disease pandemics 3, 4 nasal vs. oropharyngeal specimens 171
limitations 74 urban population 172
lives lost 275 younger population 165
mathematical model approach, Indian
scenario 65–70, 67, 68, 68, 69 DAG see directed acyclic and acyclic network
mathematical models 6–7, 9, 9–10, 18–27 graphs (DAG)
modeling approaches 3–4 data-driven assessment 304
mode of transmission 13 data-driven decision support model
mortality due to 2, 2 Bayesian support network decision model
non-government sectors 102, 112 267–269
nonpharmaceutical interventions 213 Burnt Finger Poisson distribution 258
optimization of cases, transition matrix communication-driven model 254
95–96 document-driven model 254
Index 357
inverse Gaussian distribution 259 door-to-door services lack 323

model results 260–267 Dundee stress scale 111
knowledge-driven model 255
Maxwell–Boltzmann (MB) distribution 259 The Economic Times 4
model-driven decision support system effective policies and procedures
255–256 auditable standard 315
model formulation 256–258 consultation 315
reciprocal distribution 258–259 employees in policies and procedures 316
SARS-Cov-19 crisis 253, 254 policies and procedures 315, 316
Skellam distribution 258 policy implementation 316
Davis, C. E 200 policy realistic 315–316
death rate 260–261 procedures regularly 316–317
decision-making process 226, 310 workplace policies and procedures 317
DeepFace 58 efficacy 184
DeepMind 58 “emergency” declaration 328
delta plus variant 217–218 emergency, rationality 304–308
delta variant 218 Emergency Use Authorization (EUA) 175, 181, 305
Demongeot, J. 6 employees in policies and procedures 316
Department of Health Research (DHR) 313 endemic equilibria 21–25
dependent variable 222 endemic free equilibrium (EFE) 25
deterministic fitted epidemiological model 51 Epidemic Diseases Act 307, 326
deterministic model 7 epidemic equilibria 21–25
diagnosis test model 347 epidemiological methods 307
dideoxyribonucleotides (ddNTPs) 119, 120, 121 epidemiological model approach 36–37
direct contact 27 Gauss–Markov Theorem (GMT) 38–42, 39, 42
directed acyclic and acyclic network graphs Gauss–Markov weighted least squares
(DAG) 267, 270 analysis 44–46
direct way of transmission 27 maximum likelihood estimation (MLE) 43
Disaster Management Act 307, 326 model formulation 37–38
disease-free equilibrium (DFE) 25, 48 epidemiological risk assessment model 28–36,
disease impact 219 34–36
disease prediction 219 EP model 52–56
DNA gene sequencing 117 E484Q mutation 152
alignment parameters 146 Esteva, L. 48
Cauchy distribution 126, 126, 127 “expanded access” program 305
COVID sequencing 146–147 exponential distribution 127, 127, 128, 260
exponential distribution 127, 127, 128 exponential smoothing model 80, 140, 141, 142,
gamma distribution 128, 129, 129 292, 294
gene sequencing alignment 145–146 exponential structural smoothing model 289
Illumina Solexa sequencing 134–139
logistic regression distribution model factor analysis (FA) 240
131, 131, 131 practical approach of 240
log-normal distribution 129–130, 130, 130 unrotated factor loadings 246
long-read sequencing methods (see long-read false sense of security 164
sequencing methods) FCV-19S scale 106, 107, 107
Maxam and Gilbert method 118, 119 FDA vaccine guidance 305
next-generation sequencing (NGS) 134, 134 fear and anxiety levels
poisson distribution 132, 132, 132 adaptive invasive response 103
pyrosequencing 144–145, 145 anxiety score 112, 113
RNA vs. DNA 117, 117–118 behavioral changes 103
sanger sequencing (see sanger sequencing) confounding effect, watching TV/
Weibull distribution model 133, 133, 133 social media 105, 105
DNA vaccine 176, 177 emotional feeling 103
document-driven model 254 healthcare professionals 111–112
358 Index
fear and anxiety levels (cont.) health policy 79, 219

multiple linear regressions 105, 106 health policy and systems research (HPSR) 312
QOL correlation 113, 114 health policy research 313–315
questionnaire 102–103 health professionals responsibilities 324–326
respondents, age of 103, 104, 105 health-related outcomes 301
social media/watching TV 103, 105, 111 health service center 247
stigma 107, 108–109, 109–110, 112 herd immunity 176
fitted agent-based model 7 assessment 185
fitted model 6–7, 26–27 Bayesian evaluation test statistics 213
forward bifurcation 29 comorbidity 189, 189
four-set Venn diagram, significantly correlation with BMI 188, 188
differentially expressed genes Frontline Healthcare Professionals 190, 191
(SDEGs) 125, 126 hospital-based secondary data 186–187
frequentist approach 225, 226 immigrant population 189–190, 190
immunization programs 186
gamma distribution 128, 129, 129, 257, 264, 266 limitation 185
gap analysis 301 minimum proportion of population 186
Gaussian normalcy model 154 prevalence of disease 190, 190
Gauss–Markov Theorem (GMT) 38–42, 39, 42 prime factor, disease eradication 189
Gauss–Markov weighted least squares analysis selection of target population 193, 193
44–46 types 184, 185
gene alignment 148 vaccination coverage, Russia 191–192,
global alignment 148–149 193, 194
scoring matrices 149, 149 vaccine efficacy, estimation of 187, 187
sequencing 145–146 Hethcote, H. W. 48
generalized linear model Heydari S.T. 249
model 342–344 hidden Gauss–Markov Theorem (HGMT)
model assumptions 345 62–65, 64–65
model structure 345 “high-risk” group 329
objective 345 high-risk populations 304
geometric disease progression 217 Hinkley, D. V. 51
Gilbert, W. 118 HIV/AIDS control 303
global alignment 148–149 Hoff, M. 58
Google Brain 58 Holt–Winters exponential model 194–195
government and public responsibilities 312–313 Holt–Winters (HW) triple exponential
government health policy 248 smoothing method 80–81
government policies lack 324 homoscedasticity 39–40
Greenhalgh, D. 48 honesty 340
growth model 7 Hong Zhang 6
Gumel, A. B. 51 Hsieh, Y. H. 51
Guo, S. 48 Hulley, S. 27
human interventions 340
Hahn, Stephen 305 human subject protection 341
Hamer M. 249 hydroxychloroquine 4
Hara, T. 51 hygiene and preventive measures 245
Harrell–Davis quintiles 200, 201–203
hazards regression model 37–38 Iavicoli S. 237
HD estimation 200, 203 ICMR see Indian Council of Medical
HDI see health domain-Human development Research (ICMR)
index (HDI) IDSP see Integrated Disease Surveillance
health care workers 79, 261 Programme (IDSP)
health domain-Human development index Illumina Solexa sequencing 134, 135
(HDI) 253 different platforms 137
Index 359
flowchart 138, 138 long-read sequencing methods

massive parallel signature 136, 136 massive parallel signature sequencing
procedure 136–139 (MPSS) 123–125
quality scores 139 nanopore DNA sequencing 122, 123, 124
implementation policy 309, 314–315 single-molecule real-time (SMRT)
pilot study for 318–320 sequencing 122
implementation research methods 310 SOLiD sequencing 121
incubation carrier 12 statistical methods, testing MPSS data 125, 126
India low- and middle-income countries (LMICs) 311
COVID deaths in 217 L452R mutation 152
delta plus variant 217
first wave 217 machine learning model 57, 57–59, 59, 194–195, 253
legal framework 326–328 hidden Gauss–Markov Theorem (HGMT)
second wave 217 62–65, 64–65
Indian Administrative Service (IAS) 325 measurement error (u) 60
Indian Council of Medical Research (ICMR) stochastic error (u) 60–61
164, 217, 219, 232 MADALINE 58
Indian Health Policy 328 Mallet, A. 51
innate (inherent) herd immunity 185 Marco-Franco, J. E. 214
innate immunity 175 Markov chain model 96, 97
insecticide-treated bed nets (ITNs) 310 massive data sets 253
Integrated Disease Surveillance Programme massive parallel signature sequencing
(IDSP) 301 (MPSS) 123–125
integrity 340 statistical methods, testing data 125, 126
International Health Policy 328–329 mathematical model 212
intervention model 25 COVID vaccination 180
inverse Gaussian distribution 259 flowchart, with or without vaccination 191
model results 260–267 mathematical model, prediction of novel
ITNs see insecticide-treated bed nets (ITNs) Coronavirus 18–19
Iwami, S. 51 disease simulation 24
endemic equilibria 21–25
Jentsch, P. C. 214 epidemic equilibria 21–25
Johnson, L. 51 transmission rate 24
variables used, model building 19, 19–21, 20
Kermack, W. O. 48 mathematical models 219
Khachatryan, K. A. 185 Maxam, A. 118
k-NN model 228 Maxam and Gilbert method 118, 119
knowledge-driven model 255 maximum likelihood estimation (MLE) 43
Maxwell–Boltzmann (MB) distribution 259
Laplace distribution 257, 264, 265 MC stochastic model 96–97
latent growth model 38 mean value theorem (MVT) 221
least squares estimator (LSE) 41 measurement error (u) 60
legality 341 medical facilities lack 323
leprosy elimination 303 Melesse, D. Y. 51
level of agreement 103 methodology 300–302
Levy distribution 257 Milian, J. 51
linear regression fixed model 222 Miller I.F. 234
link function 346 Model 1 291
lipid nanoparticles (NLPs) 177 model construction
Logarithmic distribution 257, 266 age-specific model parameters 276
logistic regression distribution model 131, 131, age-standardized rate 276
131, 223, 224, 231 age-wise breakup 277, 278
log-normal distribution 129–130, 130, 130, 259, 264 output 277
360 Index
model-driven decision support (MDDS) International Health Policy 328–329

system 255–256 leprosy elimination 303
model formulation 178, 256–258 methodology 300–302
rejection of vaccination 178–179 need and ensuring quality 311
Monte Carlo simulation 228 objective of 300
Moore, S. 185, 213 public feedback propagation 321–322
moving average method 196 public health and social measures
mRNA vaccines 176 administrative commitment lack 322
multilevel factor analysis 245, 247 door-to-door services lack 323
multiple logistic regression 222 government policies lack 324
multiple regression analyses 105, 105 medical facilities lack 323
ordinary least squares 106 poor safety culture 322
multiplicative method 81 proper communication lack 324
multi-system inflammatory disease of children public stigmatization 324
(MIS-C) 232 resources lack 323
multi-system inflammatory syndrome safety commitment lack 322
(MIS-C) 245 strict enforcement lack 323
MVT see mean value theorem (MVT) support at community level 322–323
social and economic attributes 308–309
naive Bayes algorithms 227, 228 take-home message 331–332
nanopore DNA sequencing 122, 123, 124 tuberculosis control 302–303
Narasimha Murthy, B. 301 uniform civil code formulation 320–321
National Commission on Macroeconomics and vector-borne disease control 304
Health (NCMH) 313 WHO policy 330
National Executive Committee 326 National Health Research Policy 313
National Expert Group on Vaccine National Rural Health Mission (NRHM) 313
Administration for COVID-19 National Urban Health Mission (NUHM) 313
(NEGVAC) 181 need and ensuring quality 311
National Health Policy next-generation sequencing (NGS) 134, 134
broad research spectrum 310–311 non-discrimination 341
challenges 317–318 non-probability snowball sampling technique 102
collaborative endeavour 310 numerical model output 241–248
COVID-19 pandemic control 302 Nuraini, N. 212, 213
effective policies and procedures auditable
standard 315 objective risk stratification (ORS) 241
consultation 315 objectivity 300, 340
employees in policies and procedures 316 OmicsBox 125
policies and procedures 315, 316 OpenAI 58
policy implementation 316 openness 340
policy realistic 315–316 opportunistic infections (OIs) 228
procedures regularly 316–317 ordinary least squares (OLS) 45, 62
workplace policies and procedures 317 ORS see objective risk stratification (ORS)
emergency, rationality 304–308 OSH national system 237
government and public responsibilities Otoo, D. 7
312–313 Oxford Nanopore Technologies 122
health policy research 313–315
health professionals responsibilities 324–326 Pacific Biosciences (Pacbio) 122
“high-risk” group 329 Pareto distribution 257, 263
HIV/AIDS control 303 Pareto, Vilfredo 263
implementation policy 309, 314–315 partial differential equation (PDE) 6
pilot study for 318–320 patrimonial model 157
India, legal framework 326–328 PDF see probability density function (PDF)
Indian Health Policy 328 PDSA cycle 319
Index 361
Pfizer–BioNTech vaccine 181 proper communication lack 324

Phred encoding. 140, 143–144 public stigmatization 324
phylogenetic models 6 resources lack 323
phylogenetic trees study 156–157 safety commitment lack 322
pneumonia 7 strict enforcement lack 323
poisson distribution 132, 132, 132 support at community level 322–323
Poisson process 258 public health emergency 237
policies and procedures 315, 316 public policy 301
policy, definition 300 public stigmatization 324
policy design and adoption 317 pyrosequencing 144–145, 145
policy implementation 307, 316
policy implications 243 quality of life (QOL) 105–106, 175, 299, 301
policy maker 311 correlation 113, 114
policy realistic 315–316 quality score 140, 141, 142
poor safety culture 322 quantitative technique 301
population density 264 quarantine and isolation 307
positivity rates 228, 229
power law function 263 random error 348–350
prediction dynamics model 219 random state components 346
predictive approach 157 Random Walk Markov Chain Stochastic
predictive modeling 194–195 Transient (RMCST) model 92–95, 95
ACF residual plot 198, 199 rape victims 340
extrapolation, COVID-19 outbreak 197, 198 Rayleigh distribution 257, 264, 265
Harrell–Davis quintiles 200, 201–203 realistic approach 253
HD estimation 200, 203 real probability 220, 221, 225, 227
interpolation of model–expected cases real-time polymerase chain reaction (RT-PCR)
196, 197, 199 97, 97–98
model construction 194–195 real-time reverse transcriptase PCR (RT-PCR)
population-level quintiles 200 asymptomatic cases 170, 170–171
vaccination coverage in India 204 cycle threshold (Ct) values (see cycle
prevention strategies 231, 237 threshold (Ct) values)
probabilistic graphical method 267 diagnostic procedure 163
probability density function (PDF) 256 model formulation 166–167, 166–168
probability values 226 output 168–171
procedures regularly 316–317 positivity rate 170–171, 171
projection modeling 205 predicted probability outcomes 169, 169
classical vs. COVID-19 vaccines 209 technique 163
forecasting figures, phase I vaccination VL RNA, detection of 164, 165
coverage 207, 208 reciprocal distribution 258–259
F-test, vaccination 205–206 regression model output 262
I Dose vs. II Dose 207, 207 religious mass gathering 238
model output 206–209 reproduction number approach 53–56,
projection models 79 55–56, 56
proof-of-principle projects 319 research ethics
proper communication lack 324 in human interventions 340
protein subunit viral vaccine 176, 177 importance of 337–338
public feedback propagation 321–322 research hypothesis 350–351
public health and social measures research implications 342
administrative commitment lack 322 resources lack 323
door-to-door services lack 323 responsible publication 341
government policies lack 324 right-skewed distribution 258
medical facilities lack 323 “right to try” movement 305
poor safety culture 322 Rihan, F. A. 47, 48
362 Index
risk analysis Skellam distribution 258, 267

behavioral risk factors 246 skill-based techniques 253
chronic lung diseases 245 Smith, H. L. 51
data frequency weightage 244 social and economic attributes 308–309
defined 237 social mobility measures 247
discussion 248–250 social science methods 300
fundamental basic principles 238 SOLiD sequencing 121
model construction 239–241 Spanish flu 219
numerical model output 241–248 spelled-out policy 314
religious mass gathering 238 spike protein variants 268
risk model in health science 238 statistical ethics
risks and benefits assumptions of 346
confidentiality 340 Bayesian analysis 347–348
human subject protection 341 random error 348–350
legality 341 research hypothesis 350–351
non-discrimination 341 systematic error 350
responsible publication 341 discussion 351–352
generalized linear model
Saad Roy, C. M. 185 model 342–344
safety commitment lack 322 model assumptions 345
sanger sequencing 118, 119 model structure 345
chain termination PCR method 119, 120 objective 345
DNA sequence, identification of 120–121 information criteria 347
long-read sequencing methods (see long-read link function 346
sequencing methods) model diagnosis test 347
size-based separation, gel electrophoresis 120 model selection 345
sanitizer usage 243 random state components 346
SARS-CoV-2 see COVID-19 research ethics in human interventions 340
SARS-Cov-2 217 importance of 337–338
SARS-Cov-19 research implications 342
data-driven model 255 risks and benefits
health risk assessment tools 237 confidentiality 340
pandemic crisis 239 human subject protection 341
SARS-Cov-2 attributes legality 341
model construction 220 non-discrimination 341
prior and posterior probability values 227 responsible publication 341
SARS-Cov-19 crisis 253, 254 statistical implications 341
Satterfield, B. C. 28 systematic components 346
scoring matrices 149, 149 testing research hypotheses 342
second wave in India 217 statistical implications 341
sensitivity analysis 213–214, 226 statistical methods
sequencing annotations 156 testing MPSS data 125, 126
Sergeev, A. 185 statistical model 27–28, 176, 179, 212
serial correlation 198 stigma 107, 108–109, 109–110, 112
serial dependency 198 stochastic convergence simulation 253
Serrana Province of Brazil 232 stochastic convergent model 293
Seventh Schedule of the Indian Constitution 326 stochastic error (u) 60–61
sexual harassment 337 stochastic time series analysis 79
Shekhar, K. 156 exponential smoothing 80
significantly differentially expressed genes Holt–Winters (HW) triple exponential
(SDEGs) 125, 126 smoothing method 80–81
simple analytical model 212 strict enforcement lack 323
single-molecule real-time (SMRT) sequencing 122 structural stochastic model 290
SIR mathematical model 232 structural time series model 10, 282
Index 363
structured questionnaire 102–103 uniform civil code formulation 320–321

suitable mathematical equation 239 US Centers for Disease Control and Prevention
support at community level 322–323 (CDC) 231
surge projection US Food and Drug Administration (FDA) 304
Bayes weighted regression model 221–226
discussion 232–234 vaccination effect, estimation of 209, 210
Frequentist and Bayesian approache 230 variant of concern (VOC) 217
model construction 220–221 variation, coefficient of 222
conditional probabilities 220, 221 vector-borne disease control 304
SARS-Cov-2, attributes 220 Verelst, F. 185
model results 226–231 Villela, D. A. M. 6
calculation summary 231–232 viral vector vaccines 176, 177
projective model 231 VL RNA 164, 165
sensitivity analysis 226 VOC see variant of concern (VOC)
susceptible-infectious-susceptible (SIS) V-safe smartphone app 181
stochastic process models 4
susceptible–infective–recovered (SIR) 47–48 Wang, N. 51
formulation 49–50 Weibull distribution model 133, 133, 133,
model discussion 50–52 260, 262
Susceptioble – exposed – Infection and whole genomic analysis (WGA) 149–155,
recovered (SEIR) model 214 150–151, 175
systematic components 346 correlation matrix of distance 153
systematic error 350 E484Q mutation 152
Gaussian kernel density 157, 157, 158
take-home message 331–332 L452R mutation 152
testing research hypotheses 342 maximum density of gene mutation 154, 154
third wave 219 scale of measurement 155
Bayesian IA score 231 virulence 152
in children 243 workplace policies and procedures 317
of COVID-19 241, 242 World Health Organization (WHO) 328
Thompson iteration method 80 policy 330
three-dimensional dynamic model, regulations 323
HIV infection 22 SARS-Cov-2 Variants 218
time series stochastic model 278
transplacental transmission 27 Zheng P. 234
Trump, Donald 304 Zhou, R. 185
tuberculosis control 302–303 Z-test 125
Taylor & Francis eBooks
www.taylorfrancis.com
A single destination for eBooks from Taylor & Francis

with increased functionality and an improved user
experience to meet the needs of our customers.
90,000+ eBooks of award-winning academic content in

Humanities, Social Science, Science, Technology, Engineering,
and Medical written by a global network of editors and authors.
TAYLOR & F RANCIS EBOOKS OF FERS:
Improved
A streamlined A single point search and
experience for of discovery discovery of
our library for all of our content at both
customers eBook content book and
chapter level
REQUEST A FREE TRIAL

support@taylorfrancis.com

Covid

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Covid

Uploaded by

Copyright:

Available Formats

COVID Transmission

and by CRC Press

CRC Press is an imprint of Taylor & Francis Group, LLC

© 2022 DM Basavarajaiah and B Narasimha Murthy

Library of Congress Cataloging‑in‑Publication Data

ISBN: 9781032069708 (hbk)

All victims of Novel Coronavirus 2019

1. Mathematical Modeling Approach to COVID-19: Vetted Real Data........................... 1

1.16 Study Limitations......................................................................................................... 74

3. Study of Anxiety and Fear of COVID-19........................................................................ 101

4. COVID-19 Gene Sequencing Modeling......................................................................... 117

4.14 Model Formulation.................................................................................................... 140

5. Real-Time PCR (RT-PCR) for COVID-19 Diagnosis and Changes in

6. COVID-19 Vaccination Modeling Approach to Public Health Policy...................... 175

7. Trend of COVID-19 Surge Projection............................................................................. 217

8. Risk Analysis of COVID-19—Vetted by Real Data Sets............................................. 237

9. Data-Driven Decision Support Model for COVID-19................................................. 253

10. Age-Specific SARS-Cov-19 Incidence Modeling.......................................................... 275

11.2 What Is Health Policy?..............................................................................................300

11.17.5  Lack of Resources for Implementing Public Health and Social

12.8  Model Selection..........................................................................................................345

parameters when diagnosing COVID-19 using RT-PCR. Chapter 6 describes a COVID-19

Dr. DM Basavarajaiah is Associate Professor and Head,

Prof. B Narasimha Murthy is a well-known academician

1.1.1 Main Objectives of This Book

(2020) proposed a mathematical model to simulate chikungunya spread; the compartmen-

1.2 Anatomical Structure of COVID-19 Virus

1.3 Virus Incubation Period

Type of Portal exit

Clinical cases (mild, Duration

Severely infected Asymptomatic Symptomatic

1.3.2 Case Fatality Rate (CFR, %)

No. of deaths from a specified disease at defined period of time

1.3.3 COVID-19 Transmission Mechanisms

1.4 Epidemiological Aspects of nCov2019 (SARS-Cov-19)

Droplets generated Touching a

1.5 Economic Impacts of Novel Coronavirus

1.6 Mathematical Model for the Prediction of

1.6.1 Variables Used for Model Building

Suscepble Infecon Treated (T)

Recovered Death (D)

Sh Susceptible population β vh Rate of infectiousness of human

where c is constant parameters.

1.6.2 Endemic and Epidemic Equilibria

Differentiating w. r. t. “t”, we get the dynamic vector model (DVM).

highly effective in mitigating future outbreaks. This conclusive description is sometimes

1.8 Epidemiological Model for the Estimation of Hazard

• Direct contact—physical contact with body parts of an infected person, such as

1.8.1 Formulation of the Epidemiological Risk Assessment COVID Model

∑ log Y = N log α + log β ∑ x

∑X log Y = log α ∑ X + log β ∑ x

After antilog substitution, equation (1.5) becomes

Yt =  log α + xn log β + xn2 log c  (1.15)

When t = 0, N = N0; therefore, c = ln N0.

Agent pathogen Environment Host Management Policy

Characteristics Characteristics Characteristics

Virulence (x2) Physical structure (x2) Prior exposure(x2)

Prevention services(x3) Immunize(x2)

0.2 PD Linear (PD)

1.9 Epidemiological Model Approach of New Diseases

( exp z )(1 + exp z ) − ( exp z )2

1.9.1.1 Latent growth model of novel coronavirus

1.9.2 Gauss–Markov Theorem (GMT)

1.16 Study Limitations......................................................................................................... 74

11.2 What Is Health Policy?..............................................................................................300

11.17.5 Lack of Resources for Implementing Public Health and Social

12.8 Model Selection..........................................................................................................345

1.1.1 Main Objectives of This Book

1.2 Anatomical Structure of COVID-19 Virus

1.3 Virus Incubation Period

1.3.2 Case Fatality Rate (CFR, %)

1.3.3 COVID-19 Transmission Mechanisms

1.4 Epidemiological Aspects of nCov2019 (SARS-Cov-19)

1.5 Economic Impacts of Novel Coronavirus

1.6 Mathematical Model for the Prediction of

1.6.1 Variables Used for Model Building

Suscepble Infecon Treated (T)

1.6.2 Endemic and Epidemic Equilibria

1.8 Epidemiological Model for the Estimation of Hazard

1.8.1 Formulation of the Epidemiological Risk Assessment COVID Model

1.9 Epidemiological Model Approach of New Diseases

1.9.2 Gauss–Markov Theorem (GMT)

CI ( 95% ) = exp ( ln ( RR ) − 1.96SE ln(RR )  to exp ( ln ( RR ) + 1.96SE ln ( RR ))

1.9.3 Maximum Likelihood Estimation (MLE) of Gauss–Markov Theorem (GMT)

1.9.4 Gauss–Markov Weighted Least Squares Analysis

1.10.2 SIR Model Discussion

1.11 EP Model with Varying Population

1.11.1 Reproduction Number Approach to Binomial Distribution (R 0)

1.12 Machine Learning Model for SARS-Cov-19

1.12.1 Machine Learning Model

1.13 Models of Machine Learning

1.13.3 Hidden Gauss–Markov Theorem (HGMT)

1.14.1 M odel Formulation

2.2 Time Series Stochastic Models

2.2.2 Holt–Winters (HW) Triple Exponential Smoothing Method