•COVID 19

History of Covid-19 Pandemic

• The Pandemic of SARS-CoV-2 (Covid-19) originated from the

Wuhan City in China in December 2019.
• On 5 January 2020, the WHO said that one in ten people around
the world (around 800 million) may have been infected with
COVID–19.
• As of 8 January 2020, 36.2 million cases have been reported
across 188 countries and territories with 
more than 1.05 million deaths; more than 25.2 million people
have recovered.
• On 11 March, WHO declared Covid-19 as a pandemic.
Clinical Features
• Incubation period: 2-14 days
• Fever
• Cough
• Shortness of breath
• Fatigue
• Hyperleukocytosis
• Lymphopenia
• Pneumonia
• ARDS
• Shock
• Arrhythmia
• Cardiac injury.
Comorbidities (more risk of severity)
• Asthma
• COPD
• Diabetes
• Hypertension
• Cardiac injury
• Cancer
• CKD
• More than 65 years
• Children < 10 years relatively spared
Samples for testing

There are different types of coronavirus tests that can be done: 

• Swab Test – In this case, a special swab is used to take a sample from your
nose or throat
• Nasal aspirate – In this case, a saline solution will be injected into your nose
and, then a sample is taken with a light suction
• Tracheal aspirate – In this case, a thin tube with a torch, also known as a
bronchoscope, is put into your mouth to reach your lungs from where a
sample is collected. 
• Sputum Test – Sputum is thick mucus that gets accumulated in the lungs and
comes out with a cough. During this test, you’re required to cough up sputum
in a special cup or a swab is used to take a sample from your nose. 
• Blood test – In this case, a blood sample is taken from a vein in the arm. 
Diagnostic tests

• Two kinds of tests are available for COVID-19:

• viral tests
• antibody tests.
• A viral test indicates a current infection.

• An antibody test indicates a present as well as past infection.

 Diagnostic tests developed
RT-PCR
• Polymerase chain reaction (PCR) is a process that amplifies (replicates) a small, well-defined
segment of DNA many hundreds of thousands of times, creating enough of it for analysis.
Test samples are treated with certain chemicals that allow DNA to be extracted. 
Reverse transcription converts RNA into DNA.
• Reverse transcription polymerase chain reaction (RT-PCR) first uses reverse transcription to
obtain DNA, followed by PCR to amplify that DNA, creating enough to be analyzed. RT-PCR
can thereby detect SARS-CoV-2, which contains only RNA. The RT-PCR process generally
requires a few hours.
• Real-time PCR  provides advantages including automation, higher-throughput and more
reliable instrumentation. It has become the preferred method.
• Average sensitivity for rapid molecular tests were 95.2% (ranging from 68% to 100%) and
average specificity was 98.9% (ranging from 92% to 100%).
• Sensitivity of clinical samples by RT-PCR is 63% for nasal swab, 32% for pharyngeal swab,
48.1% for feces, 72-75% for sputum, and 93-95% for bronchoalveolar lavage
Antigen Testing

• An antigen is the part of a pathogen that elicits an immune response.

Antigen tests look for antigen proteins from the viral surface.
• In the case of a coronavirus, these are usually proteins from the 
surface spikes. SARS-CoV-2 antigens can be detected before onset of
COVID-19 symptoms (as soon as SARS-CoV-2 virus particles) with
more rapid test results, but with less sensitivity than PCR tests for the
virus.
 Rapid Tests

• Rapid diagnostic tests based on antigen detection

A rapid test has also been started for the COVID-19, which involves
taking samples from the nose, throat, and lungs. This ensures a speedy
and accurate diagnosis and its usage is CDC-approved. 
• Rapid diagnostic tests based on host antibody detection
This test detects the presence of antibodies in the blood of COVID-19
infected people.
Rapid Diagnostic Tests

• Rapid diagnostic tests based on antigen detection

• A rapid test has also been started for the COVID-19, which involves
taking samples from the nose, throat, and lungs. Rapid diagnostic test
(RDT) of a sample of the respiratory tract of a person helps to detect
the viral proteins (antigens) related to COVID-19 virus. This ensures a
speedy and accurate diagnosis and its usage is CDC-approved. 
• Rapid diagnostic tests based on host antibody detection
• This test detects the presence of antibodies in the blood of COVID-19
infected people. The strength of antibody response depends on
several factors like age, medications, infections, and severity of
disease etc.
Antibody tests

•  Automated analyzer for immunoassays, used to find SARS-CoV-2 antibody test.

• The body responds to a viral infection by producing antibodies that help neutralize
the virus. Blood tests (serology tests) can detect the presence of such antibodies.
Antibody tests can be used to assess what fraction of a population has once been
infected, which can then be used to calculate the disease's mortality rate.

• SARS-CoV-2 antibodies' potency and protective period have not been established. [ A
positive antibody test may not imply immunity to a future infection

• The most notable antibodies are IgM and IgG. IgM antibodies are generally detectable
several days after initial infection. IgG antibodies generally become detectable 10–14
days after infection and normally peak around 28 days after infection. 

• Generally, however, median IgM detection occurs 5 days after symptom onset,
whereas IgG is detected a median 14 days after symptom onset.  IgG levels
significantly decline after two or three months.

• Average specificity of antigen tests is 99.5%, and average sensitivity is 56.8

 Different Types of Coronavirus Tests
  Molecular Test
Tests Diagnostic test, viral test,
molecular test, nucleic acid
amplification test (NAAT), RT-PCR
test, LAMP test
Antigen Test
Rapid diagnostic test
(Some molecular tests are
also rapid tests.)
Antibody Test
Serological test, serology, blood
test, serology test

How the sample Nasal or throat swab (most tests) Nasal or throat swab Finger stick or blood draw
is taken...
Saliva (a few tests)

How long it takes Same day (some locations) One hour or less Same day (many locations)
to get results...
or up to a week or 1-3 days

Is another test This test is typically highly
needed... accurate and usually does not
need to be repeated.
Positive results are usually Sometimes a second antibody
highly accurate but negative test is needed for accurate
results may need to be results.
confirmed with a molecular
test.

What it shows... Diagnoses active coronavirus
infection
What it can't do... Show if you ever had COVID-19
or were infected with the
coronavirus in the past
Diagnoses active
coronavirus infection
Rule out active coronavirus
infection. Antigen tests are
more likely to miss an active
coronavirus infection
compared to molecular
tests.
Shows if you’ve been infected by
coronavirus in the past
Diagnose active coronavirus
infection at the time of the test
or show that you do not have
COVID-19. IgM 5 days after
symptom onset, IgG 14 days
after symptom onset.  IgG
decline after two or three
months.
 Imaging
• Typical visible features on CT initially include bilateral multilobar 
ground-glass opacities with a peripheral or posterior distribution. 
• COVID-19 can be identified with higher precision using CT than with RT-PCR
•  Chest CT scans and chest x-rays are not recommended for diagnosing
COVID-19.
• Radiologic findings in COVID-19 lack specificity
 Virology
 Coronaviruses are positive-sense,
single-stranded enveloped RNA
viruses with helical capsids that infect
a wide range of hosts including
humans, bats, other mammals, and
birds

 Further sub-classified into four

genera: alpha, beta, delta, and
gamma coronaviruses, of which alpha
and beta coronaviruses are known to
infect humans.
Virology

• Coronaviruses have the largest genome of all ribonucleic acid (RNA)

viruses infecting human
• Microscopically coronaviruses have club-shaped trimeric surface
spike glycoproteins that give the virions the appearance of a crown,
hence their name (from the Latin corona meaning “crown”).
• Coronaviruses contain four major structural proteins: the spike (S),
hemagglutinin-esterase (HE) in some beta corona viruses, membrane
(M), and envelope (E) all located on the membrane envelope, and the
nucleocapsid (N) protein found in the core.
Virology

• The S surface protein plays key roles in the viral life cycle and in host
defense: it is responsible for receptor binding, host range, membrane
fusion, hemagglutinin activity, and is a target for eliciting host
neutralizing antibodies
Pathogenesis
Pathogenesis
• SARS-CoV-2 enters host cells through interacting with ACE2,
an interferon-induced gene expressed on type 2
pneumocytes, intestinal epithelial cells, nasal goblet
secretory cells olfactory epithelial support cells and stem
cells, and nasal respiratory epithelium
Like pulmonary epithelial cells, vascular endothelial cells express ACE2, and SARS-
COV-2 has been found inside of endothelial cells in pulmonary capillaries, leading to
inflammatory cytokine production, endothelial cell death, and endothelial barrier
disruption.

This endotheliitis is associated with diffuse thickening of the alveolar wall and
infiltration of mononuclear cells and macrophages into the airspaces, which
collectively are seen as ground-glass opacities in the lungs on CT imaging As the
inflammation progresses, pulmonary edema and hyaline membrane formation
occur and cause acute respiratory distress syndrome (ARDS), which interferes with
oxygen diffusion.
Transmission
Transmission

• Intermediate host
• Wuhan Fish market
• Aerosol
• Fomites
• Gastrointestinal tract
• Conjunctiva
• Vertical transmission
 Immunology
• Like pulmonary epithelial cells, vascular endothelial cells express ACE2, and
SARS-COV-2 has been found inside of endothelial cells in pulmonary
capillaries, leading to inflammatory cytokine production, endothelial cell
death, and endothelial barrier disruption.
• This endotheliitis is associated with diffuse thickening of the alveolar wall
and infiltration of mononuclear cells and macrophages into the airspaces,
which collectively are seen as ground-glass opacities in the lungs on CT
imaging As the inflammation progresses, pulmonary edema and hyaline
membrane formation occur and cause acute respiratory distress syndrome
(ARDS), which interferes with oxygen diffusion.
Immunology

• Activation of the coagulation cascade and consumption of clotting

factors have been associated with severe COVID-19.

• In one study, 71% of patients who died of COVID-19 met criteria for
disseminated intravascular coagulation (DIC)
Cytokine storm

• Cytokine storm is when a hyperimmune reaction occurs and abnormally

high quantity of cytokine proteins are released into the blood too quickly
• Acute respiratory distress syndrome (ARDS) is the main cause of death in
COVID-19 disease. It further states that one of the main features of ARDS
is the cytokine storm – an uncontrolled systemic inflammatory response
resulting from the release of pro-inflammatory cytokines by immune
activated cells.
• High blood levels of cytokines have been detected in patients with
COVID-19 infection.
Effect of Cytokine storm

• In a COVID-19 patient, cytokine storm starts in lungs, which is why

the lungs get affected initially, then as the storm loses control and
starts attacking other organs which lead to multi-organ failure. As
oxygen starts decreasing in the body, it starts working inefficiently
including the immune system.
Intervention

• Hypoxia- the state of insufficient oxygen as it kills cells, which leads to

multiple organ failure like kidney failure, heart failure and even
impact
• Various drugs such as anti-tumour necrosis factor, cyclooxygenase
inhibitors, are potential cytokine storm inhibitors. Some of them are
currently in clinical trials for COVID-19.
Drugs to stop cytokine storm

• The current evidence indicates that tocilizumab, an IL-6 inhibitor, is

relatively effective and safe.
• Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1
checkpoint inhibition, cytokine-adsorption devices,
• Intravenous immunoglobulin,
• Antimalarial agents could be potentially useful and reliable
approaches to counteract cytokine storm in COVID-19 patients.