Covid 19 Special Conditions

MANAGEMENT
GUIDELINES
FOR
COVID-19
PATIENTS WITH SPECIAL
MEDICAL CONDITIONS.
EGYPT
APRIL, 2020
COVID-19 Management with Special Co morbidities
Revised by
Name Affiliation
Professor of Chest Diseases. Head of Pulmonary
Dr.Hossam Hosny Masoud Hypertension Unit, Faculty of Medicine,
Cairo University
Professor of Pulmonary Medicine Ain Shams
Dr.Gehan Elassal
University
Professor of Hepatogastroenterology and
Dr.Samy Zaki
Infectious Diseases, Al Azhar University
Consultant of Hepatoogy, Gastroenterology and
Infectious Diseases. National Hepatology and
Dr.Amin Abdel Baki
Tropical Medicine Research Institute (NHTMRI),
Cairo, Egypt
General Director of Directorate of Fever
Dr.Hamdy Ibrahim Hospitals,
MOHP
Dr.Wagdy Amin Director General for Chest Diseases,MOHP
Professor of critical care medicine,
Dr.Akram Abdelbary Cairo University
Chairman elect of ELSO SWAAC chapter
Lecturer of critical care medicine,
Dr.Ahmad Said Abdel Mohsen
Faculty of Medicine, Cairo University
Fellow of Infectious Diseases and
Endemic Hepatogastroentrology,
Dr.Mohamed Hassany
National Hepatology and
Tropical Medicine Research Institute
Dr.Alaa Eid Head of Preventive Medical Sector MOHP
Minister's Advisor for Research and
Health Development.
Dr.Noha Asem Mohamed
Chairman of Research Ethics Committee MOHP.
Lecturer of Public Health, Cairo University.
Consultant Tropical Medicine Researcher of
Dr.Ehab Kamal Tropical Medicine.
Medical Division National Research Center
Consultant Obstetrician & Gynecologist
Dr. Mohammed Mourad Youssif
El-Galaa Maternity Teaching Hospital
Head of Hearing & Speech Institute-ENT
Dr. Ahmed M. Mustafa
consultant
Ass. consultant of ENT- Hearing & Speech
Dr. Ehab K. Sefein
Institute
Fellow of ENT- Hearing & Speech Institute.
Dr. Mohammad M. Gaballah
Professor of internal medicine and nephrology
Dr. Mohamed Salah Eldin Zaki
(National Institute of Urology and Nephrology)
Dr. Hesham Mohamed Elsayed
(Ain Shams University)
Dr. Hussein Saeed El Fishawy
(Cairo University)
Fellow(Lecturer)and Head of Clinical Pharmacy,
Critical Care Medicine Department, Head of
Dr Naglaa S. Bazan
Clinical Pharmacy Inspection Department, Cairo
University Hospitals
Assistant Professor of Critical Care Medicine,
Dr. Khalid M. Taema
1
COVID-19 Management with Special Co morbidities
Revised by
Name Affiliation
Lecturer and Senior Consultant of Critical Care
Dr. Mohamed Abo Hamila Medicine (Beni Suef University and Cairo
University)
Dr. Ahmed Badr Professor of Pediatrics, Cairo University
Dr. Hafez M. Bazaraa Professor of Pediatrics, Head of Pediatric Critical
Care Division, Cairo University
Dr. Randa Darwish Fellow of Pediatrics
General Organization for Teaching Hospitals and
Institutes
Professor, Department of Critical Care Medicine,
Dr. Akram M. Fayed, MD, ABIM
Faculty of Medicine, University of Aexandria
Professor of Internal Medicine and Nephrology,
Dr. Mohamed Salah Eldin Zaki
National Institute of Urology and Nephrology
Professor of Clinical Pathology, Faculty of
Dr. Nancy Mohamed El-Guindy Medicine, Kasr Al Aini, Cairo University
Head of the CPHL, MOH
Assistant Professor of Pulmonary Medicine,
Dr. Mohamed Said Ismail
Dr. Mohamed Seleem Mohamed Cardiology Consultant, National Heart Institute
Dr. Ashraf Ahmad Abdelmegid Cardiology Consultant, National Heart Institute
Dr. Karim Saeed Mostafa Professor of Cardiology, Cairo University
Dr. Walid El-hammady Professor of Cardiology, Ain Shams University
2
Table of Contents
Item Page
List of Tables 4
List of Figures 5
List of Abbreviations 6
1- COVID-19 in Pregnancy 8
2- COVID-19 in Children 16
3- Guidelines for Pediatric Otolaryngologic Practice in COVID-19 Positive 20
Patients
4- Guidelines of Kidney Transplantation during the COVID-19 Pandemic 31
1. 5- Guidelines for Management of COVID-19 in Kidney Failure 42
2. 6- Management of COVID-19 Patients with Liver Disease 51
7- Algorithm for Epistaxis in COVID-19 Positive Patients 54
8- Guideline Statements for Otologic Procedures in COVID-19 Positive 55
Patients
9- Guidelines for Tracheostomy on COVID19 Positive Patients 58
10- Guidelines for Tonsillitis and Quinsy in COVID-19 Positive Patients 62
11- Guidelines for STEMI 63

12- Guidelines for NSTEMI 64
13- COVID-19 and Heart Failure 65
14- Drug Related Factors to Consider during COVID-19 78
• Summary of Recommendations for Dosing and Monitoring of the
Selected COVID-19 Experimental Drugs
• Risk Categories for Most Common Drugs that Prolong QT and Induce
Torsades de Pointes (TdP)
• QTc monitoring Protocol
• Special Precautions and Monitoring Parameters in Special Populations
and in Patients with Chronic Diseases
References 116
3
List of Tables
Item Page
Table 1. Safety of Experimental and Adjunct Covid-19 Therapies in Pregnancy 14
and Lactation
Table 2. Safety of Antibiotics used in Covid-19 Disease in Pregnancy and 15
Lactation
Table 3. Evaluation of Respiratory distress: tachypnea, retractions or grunting in 23
Children
Table 4. Weight-band Dosing Table for Faripiravir in Children (age ≥ 1 y, 25
weight ≥ 10 kg) Infected with Ebola Virus Disease (Safety and efficacy not
established)
Table 5. Risk Score For Drug-Associated QTc Prolongation 68
Tab S Table 6. Summary of Recommendations for Dosing and Monitoring of the 97
sCOVI Selected COVID -19 Experimental Drugs
C
Table 7. CredibleMeds Classification of Possible COVID-19 Treatment 108
4
List of Figures
Item Page
Figure 1. Algorithm For Handling a Healthy Neonate Born to Mother with 19
Confirmed or Suspected COVID-19 Who is Able to Look after Neonate
Figure 2. Modulation of Immunosuppressive Medication for Kidney Transplant 34
during the COVID-19 Pandemic
Figure 3. Management Protocol for Dialysis Patients Suspected to have 50
COVID-19 Infection
Figure 4. Algorithm for Managing COVID-19 Patients with Liver Disease 53
F Figure 5. Algorithm for Prevention of Drug-induced Torsades de Pointes or 112
Sudden C Cardiac Death in COVID-19
5
List of Abbreviations
Abbreviation
ABO- ABO Blood Group System
ACEI Angiotensin Converting Enzyme Inhibitors
ACE2 Angiotensin-Converting Enzyme 2
ARBs Angiotensin Receptor Blockers
ARDS Acute respiratory Distress Syndrome
AST Aspartate Aminotransferase
AZA Azathioprine
CBC Complete Blood Count
CLQ Chloroquine
CIED Cardiovascular Implantable Electronic Device
3CL 3-Chymotrypsinlike
CNI Calcineurin Inhibitiors
COVID-19 Coronavirus Disease 2019
CPA cyclosporine
CRP C-Reactive Protein
CRRT Continuous Renal Replacement Therapy
CRT Cardiac Resynchronization Therapy
CVVH Continuous Veno-Venous Hemofiltration
CYP Cytochrome P450
EASL European Association for the Study of the Liver
ECMO Extracorporeal Membrane Oxygenation.
ENTUK Professional membership body representing Ear, Nose
and Throat surgery, as well as its related specialities, in
the United Kingdom
ERA/EDTA European Renal Association – European Dialysis and
Transplant Association
ESC European Society of Cardiology
ESICM European Society of Intensive Care Medicine
FAVI Favipiravir
GFR Glomerular Filtration Rate

G6PD Glucose-6-phosphate-dehydrogenase;
HBsAg Hepatitis B Surface Antigen
HCV Hepatitis C virus
HD Hemodialysis
HIV Human Immunodeficiency Virus
HRCT High Resolution Computerized Tomography
HCLQ Hydroxychloroquine
6
List of Abbreviations
Abbreviation
IHD Intermittent Hemodialysi
ILI Influenza Like Illness
INFN-ᵝ Interferon beta
IV Intravenous
LPV/r Lopinavir/ritonavir
MODS Multi-organ Dysfunction
mTORi mTOR Inhibitiors
NAT Nucleic Acid Testing
NICU Neonatal Intensive Care Unit
NIP National Immunization Program
NIV Noninvasive ventilation
NSTEMI Non-ST segment elevation myocardial infarction
PEEP Positive end-expiratory pressure
P-gp P-glycoprotein
PPE Protective Equipment
RBV Ribavirin
RDV Remdesevir
SARS-COV-2 Severe acute respiratory syndrome coronavirus 2
SLED Slow Low Efficiency Dialysis
SSC Surviving Sepsis Campaign
STEMI ST segment elevation myocardial infarction
TAC Tacrolimus
TdP Torsades de pointes
TCZ Tocilizumab
UGT1A1 UDP glucuronosyltransferase family
1 member A1.
VPDs Vaccine-Preventable Diseases
7
1. COVID-19 in Pregnancy
1.1. Introduction
Severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is a new strain of
coronavirus causing COVID-19 with an incubation period of 1-14 days.
Effect on the pregnant woman
It has long been known that, whilst pregnant women are not necessarily more susceptible
to viral illnesses, changes to their immune system in pregnancy can be associated with
more severe symptoms. This is particularly true towards the end of pregnancy.
Effect on the fetus
There are currently no data suggesting an increased risk of miscarriage or early
pregnancy loss in relation to COVID-19. Case reports from early pregnancy studies with
SARS and MERS do not demonstrate a convincing relationship between infection and
increased risk of miscarriage or second trimester loss. Maternal COVID-19 may be
associated with intrauterine growth restriction, intrauterine fetal death, and neonatal
death.
Currently, there is no evidence that the virus is teratogenic. However, very recent
evidence has suggested that it is probable that the virus can be vertically transmitted,
although the proportion of pregnancies affected and the significance to the neonate has
yet to be determined.
There are case reports of preterm birth in women with COVID-19, but it is unclear
whether this was always iatrogenic or whether some were spontaneous.
1.2. General advice

• Social distancing: pregnant women should increase their social distancing to reduce
the risk of infection and should avoid contact with people who are known to have
COVID-19 or those who show possible symptoms. Women above 28 weeks
gestation should be particularly attentive to social distancing minimizing contact
with others (STAY HOME).
• Hand washing: pregnant women should wash their hands regularly for 20 seconds
with soap and water or alcohol-based hand rub. They should not touch their eyes,
nose, or mouth if their hands are not clean.
8
• They should cover their nose and mouth with a disposable tissue or flexed elbow
when coughing or sneezing.
• They should stop smoking.
1.3. Advice for caring for pregnant women during the COVID-19
epidemic period
• Women should be advised to attend antenatal care, despite being advised to otherwise
keep social distancing. Studies have shown that if women do not attend antenatal
services they are at increased risk of maternal death, stillbirth, and other adverse
perinatal outcomes.
• Wherever possible, scans and antenatal appointments and required investigations
should be provided within a single visit in a one-step clinic, involving as few staff as
possible. Some appointments can be conducted remotely (teleconferencing and
videoconferencing) especially for women in self-isolation. At all remote
appointments, women should be asked about wellbeing and, if in third trimester, fetal
movements. If a woman is concerned about fetal movements or her physical
wellbeing, physical attendance should be advised.
• During the COVID-19 epidemic period, a detailed history regarding recent travel,
occupation, contact and clustering (TOCC) and clinical symptoms should be
acquired routinely from all pregnant women attending for routine care. The hospital
should have a system in place for identifying potential cases as soon as possible to
prevent potential transmission to other patients and staff. This should be at first point
of contact (either near the entrance or at reception) to ensure recognition and
infection control. This should be employed before a patient takes a seat in the
waiting area.
• For women who are self-isolating because someone in their household has possible
symptoms of COVID-19, appointments should be deferred for 14 days.
• Consider outpatient induction of labor for low-risk women.
1.4. Advice for caring for pregnant women with suspected or confirmed
COVID-19
9
Antenatal care
• Appointments
- For women who have had symptoms, appointments should be deferred until 7 days
after the start of symptoms, unless fever persists.
- For women who are self-isolating because someone in their household has possible
symptoms of COVID-19, appointments should be deferred for 14 days.
- Women should be advised to attend via private transport where possible.
- The hospital should allocate a separate antenatal clinic for women with suspected or
confirmed COVID-19. Remove non-essential items from the clinic room. Only
essential staff should enter the clinic and should wear the appropriate PPE.
- If ultrasound equipment is used, it should be decontaminated after each use. Ensure
surfaces of transducers are cleaned and disinfected according to manufacturer
specifications, taking note of the recommended wet time for wiping transducers and
other surfaces with disinfection agents. Consider using protective covers for probes
and cables.
• Admissions
- Pregnant women admitted to the hospital with suspected or confirmed COVID-19
should be managed with a multidisciplinary team (obstetrician, intensivist,
anesthetist, microbiologist, neonatologist, infection control specialist).
- Suspected cases should be treated in isolation and confirmed cases should be
managed in a negative-pressure isolation room. Critically ill patients should be
admitted to a negative-pressure isolation room in ICU. If negative-pressure isolation
rooms are not available, suspected patients should be isolated in single rooms, or
grouped together once COVID-19 has been confirmed.
- All attending medical staff should wear the appropriate PPE.
- It should be noted that young fit women can compensate for a deterioration in
respiratory function and are able to maintain oxygen saturation before they then
suddenly decompensate. So, a rise in the respiratory rate, even if the oxygen
saturation is normal, may indicate a deterioration in respiratory function and should
be managed by starting or increasing oxygen. Titrate oxygen to keep saturation
>94%.
10
- Chest imaging, especially CT chest, is essential for the evaluation of the unwell
patient with COVID-19 and should be performed when indicated and not delayed
because of fetal concerns. Abdominal shielding can be used to protect the fetus.
- Apply caution with IV fluid management (beware of fluid overload)
- There are some reports that even after a period of improvement there can be a rapid
deterioration. Following improvement, consider an ongoing period of observation,
where possible, for a further 24-48 hours. On discharge, advise the woman to return
immediately if she becomes unwell.
- Health professionals should be aware that asymptomatic pregnant women admitted
for obstetric conditions may develop symptoms of COVID-19 later (fever,
respiratory symptoms, lymphopenia)
• Corticosteroids for lung maturation
- There is no evidence to suggest that steroids for fetal lung maturation cause any harm
in the context of COVID-19. Tocolysis should not be used in an attempt to delay
delivery in order to administer steroids.
Intrapartum care
• Women should be advised to attend via private transport where possible.
• Staff providing care should wear the appropriate PPE.
• Women should immediately be escorted to an isolation room. Only essential staff
should enter the room.
• Once settled in an isolation room, a full maternal and fetal assessment should be
conducted by a multidisciplinary team:
- Assessment of severity of COVID-19 symptoms
- Maternal observations (temperature, respiratory rate, oxygen saturation)
- Continuous cardiotocography in labor is currently recommended for all women with
COVID-19
- If the woman attends with a fever, investigate and treat as a case of intrapartum sepsis
but also consider active COVID-19 as a cause.
• The mode of birth should not be influenced by the presence of COVID-19, unless the
woman’s respiratory condition demands urgent delivery
- Shortening of the second stage with instrumental delivery may be performed in
women who become exhausted or hypoxic.
11
- Given the lack of evidence to the contrary, delayed cord clamping is still
recommended after birth.
- Elective cesarean sections should be scheduled at the end of the operating list.
- Emergency cesarean sections should be carried out in a second obstetric theatre where
available.
- The number of staff in the operating theatre should be kept to a minimum, and all
must wear the appropriate PPE. With general anesthesia, all staff should wear the
appropriate PPE. The scrub team should scrub and wear PPE before the general
anesthesia is commenced. With regional anesthesia, all staff not required should stay
outside until the block is effective.
- There is no evidence that epidural or spinal analgesia or anesthesia is contraindicated
in the presence of COVID-19. Therefore, epidural analgesia should be recommended
in labor in women with suspected or confirmed COVID-19 to minimize the need for
general anesthesia if urgent delivery is needed.
- Miscarried embryos/fetuses and placentae should be treated as infectious tissues and
disposed of appropriately.
Neonatal management
• The baby can be cleaned and dried as normal. It is recommended to leave the vernix
caseosa in place for 24 hours as it contains antimicrobial peptides.
• Neonatologists should attend deliveries on their normal center-specific policies;
maternal COVID-19 alone is not an indication to do so. This is important to conserve
use of PPE. In addition, hospitals may reevaluate the appropriateness of institutional
traditions for mandatory attendance by the neonatologist in the delivery room at low-
risk deliveries and instead allow the neonatal team to standby to conserve PPE. If
neonatologists are needed for newborn resuscitation, they should wear the
appropriate PPE. Clinicians should not change indicated newborn care due to
maternal COVID-19.
• There is currently insufficient evidence regarding the need for mother-baby separation
and the safety of breastfeeding. If the mother is severely or critically ill, separation
appears to be the best option with attempts to express breast milk with a pump to
maintain milk production (the pump should be cleaned after each use). If the mother
is asymptomatic or mildly affected, rooming-in and breastfeeding can be considered.
Since the main concern is that the virus may be transmitted by respiratory droplets
12
rather than breast milk, breastfeeding mothers should wash their hands and wear a
mask before touching the baby and should avoid coughing or sneezing on the baby
while feeding. In case of rooming-in, the baby’s cot should be kept at least 2 meters
from the mother’s bed and a physical barrier such as a curtain may be used.
• Infants requiring neonatal intensive care optimally should be admitted to a single
room. If this is not available, infants should be maintained at least 2 meters apart
and/or placed in air temperature-controlled incubators.
• Where testing capacity is available, neonates of COVID-19 infected mothers should
be tested. If testing is not readily available, centers may opt for clinical monitoring
only. Testing infants who require neonatal intensive care should be performed to
determine the potential contribution of COVID-19 to neonatal observed illness. In
addition, testing will allow centers to conserve PPE if testing is negative.
- Testing should be done first at 24 hours of age.
- Testing should be repeated at 48 hours of age. For well newborns who will be
discharged prior to 48 hours, clinicians may consider not obtaining this test.
However, it should be noted that there have been reports of neonates who test
negative at 24 hours but positive at 48-72 hours.
• Treatment of COVID-19 infected infants mainly depends on adult patients’ clinical
experience due to few cases in infants. Symptomatic and supportive treatment is the
mainstay of therapy including the supply of oxygen, the maintenance of water-
electrolyte balance and the maintenance of acid-base balance. For infants with severe
acute respiratory distress syndrome, high-dose pulmonary surfactant, inhaled nitric
oxide, high-frequency oscillatory ventilation, and extracorporeal membrane lung
may be useful.
• Infants who test positive (or whose status can not be determined due to lack of
testing), but with no symptoms of COVID-19, may be discharged home with
appropriate precautions and plans for frequent outpatient follow-up contacts (either
by phone, telemedicine, or in-office) through 14 days after birth. Specific guidance
regarding use of masks, gloves and hand hygiene should be provided to all
caretakers.
• After hospital discharge, a COVID-19 infected mother is advised to maintain a
distance of at least 2 meters from the newborn, and when in closer proximity use a
13
mask and hand-hygiene for newborn care until at least 7 days have passed since
symptoms first appeared.
1.5. Use of drugs during pregnancy and lactation

• Any drug, even if it is not clearly safe to the fetus, should be used if the maternal
condition necessitates its use.
• No drug within the drug list for COVID-19 management indicates induction of
abortion, Tables 1 and 2. Refer to Section 14 for further guidance on drug dosing
and monitoring recommendations.
Table 1. Safety of Experimental and Adjunct Covid-19 Therapies in Pregnancy
And Lactation
Drug During Pregnancy During Lactation
Chloroquine sulfate Safe to use Safe to use
Hydroxychloroquine Category
undetermined
Lopinavir/ritonavir No safety concerns Probably safe
Favipiravir Potentially Limited data
teratogenic
Remdesivir Limited data Limited data
Tocilizumab Limited data Limited data
Azithromycin Category B Monitor infant for possible effects
on GIT flora e.g. vomiting,
diarrhea, thrush
Oseltamivir Studies suggest Safe to use
(Tamiflu) that it is its safety
14
Table 2. Safety of Antibiotics used in Covid-19 Disease in Pregnancy and
Lactation
Drug During Pregnancy During Lactation
Amikacin Category D Discontinue
Gentamycin Ototoxic & nephrotoxic breastfeeding
Levofloxacin Category C Monitor infant for

possible effects on GIT
flora
Fluconazole Increased risk of Acceptable
miscarriage
Reported skeletal &
cardiac malformations with
high doses
Piperacillin/tazobactam Category B Low levels in breast milk
No expected adverse
effects
Meropenem No controlled data Low levels in breast milk
Only use when clearly No expected adverse
needed effects
Imipenem Category C Low levels in breast milk
No expected adverse
effects
Linezolid Category C No published data
(alternate drug
preferably)
Teicoplanin Potential risk of inner ear and Unknown whether it is
renal damage to the fetus excreted in breast milk or
not
15
2. COVID-19 in Children
2.1. Children at increased risk of COVID-19 complications

1- Long term respiratory conditions e.g., severe asthma, cystic fibrosis…
2- Immunocompromised e.g., children receiving chemotherapy or high dose steroids
3- Hemodynamically significant and/or cyanotic heart disease
4- Chronic Kidney Disease stages 4, 5 or on dialysis
2.2. Assessment of children in COVID-19 pandemic

• Wear personal protective equipment (PPE)
• Oropharynx of children should NOT be examined unless essential
• If the throat needs to be examined, PPE should be worn, irrespective of whether the
child has symptoms consistent with COVID-19 or not.
• Ideally only one parent
• Patient and all family members should wear surgical masks in ED
2.3. Emergency Department

• If a child with possible COVID-19 presents directly to ED, they should be redirected
to your local COVID-19 isolation area.
• If the child has severe respiratory compromise, they will need to be transferred
immediately to your isolation cubicle for management.
• A record should be kept of all staff in contact with a possible case
• Basic pediatric resuscitation and life support
• Advanced pediatric resuscitation and life support
2.4. Clinical Manifestations of COVID-19 in Children

• Clinical Manifestations of COVID-19 are similar in children and adults, however,
children have generally mild symptoms
16
2.5. Face masks and children in COVID-19 pandemic
• CDC recommends cloth face covering for all people
• Children younger than 2 years should not wear a cloth face covering because of
concern of suffocation
2.6. Medications in Children suspected to have COVID-19

A. Immunosuppressive medications:
• Examples of medications: steroids, tacrolimus, ciclosporin, mycophenolate (MMF),
azathioprine, cyclophosphamide, sirolimus, eculizimab and rituximab
• Examples of diseases: Kidney transplant patients, nephrotic syndrome, Henoch-
Schonlein Purpura, IgA nephropathy, vasculitis (including SLE), MPGN,
membranous nephropathy, tubulo-interstitial nephritis
• Recommendations:
• Continue the immunosuppressant medications without exception.
• Relapse of the underlying condition may have higher risk than the virus itself
• Follow the general precautions
• Any fever or respiratory symptoms MUST be properly assessed
B. Antipyretics:
• Regular paracetamol is safe
• Avoid NSAIDs such as Ibuprofen/Naproxen
C. Anti-hypertensives:
• Continue any anti-hypertensive including ACE inhibitors (captopril, enalapril,
lisinopril, ramipril) and ARBs (Losartan, candesartan)
2.7. Vaccination in Children suspected to have COVID-19

• There is currently No vaccine to protect against COVID-19
• Any disruption of immunization services, even for short periods, can increase the
occurrence of VPDs (Vaccine-preventable diseases)
• National Immunization Program (NIP) should be continued without any disruption
• All newborns, infants and children should be vaccinated according to the schedule
• Consideration of the guidelines on COVID-19 infection prevention measures during
immunization sessions (avoid crowding, social distancing…)
17
• Avoid mass vaccination campaigns until the COVID-19 situation resolves
• Avoid introduction of any new vaccine in the NIP
2.8. Neonatal Management for 2019 Novel Coronavirus Infection

• Relatively few cases have been reported of infants confirmed with COVID-19; those
that have been reported experienced mild illness.
• No vertical transmission has been documented. Amniotic fluid, cord blood, breast
milk samples and throat swabs from the neonates all tested negative for the COVID-
19 virus by RT-PCR.
• Multidisciplinary consultations from obstetric, perinatal, neonatal and intensive care
specialists are essential.
Feeding neonates born to Mother with Confirmed or Suspected COVID-19
Infection
• Breast milk is the BEST source of nutrition in ALL neonates and infants
• Early initiation of breastfeeding within 1 hour of birth results in greater benefits due
to dose-response effect.
• Exclusive breastfeeding should continue for 6 months with timely introduction of

adequate, safe complementary foods at age 6 months, while continuing breastfeeding
up to 2 years of age or beyond.
• Mothers who are not able to initiate breastfeeding during the first hour after delivery
should still be supported to breastfeed as soon as they are able.
• Respiratory hygiene For all confirmed or suspected COVID-19 cases, during skin-
to-skin contact or kangaroo mother care and feeding ( medical mask when near a
child), perform hand hygiene before and after contact with the child, and routinely
clean and disinfect contact surfaces.
• Breastfeeding counselling, basic psychosocial support, and practical feeding support

should be provided to all pregnant women and mothers with infants and young
children, whether they or their infants and young children have suspected or
confirmed COVID-19.
• Mothers and infants should be enabled to remain together and practise skin-to-skin
contact, throughout the day and night, during establishment of breastfeeding,
18
whether they or their infants have suspected, probable, or confirmed COVID-19.
(WHO 13 March 2020), Figure 1.
Contact & Droplet Precautions
Room-in with Mother who can look after neonate

Confirm NP swab from mother and neonate
- Monitor neonate for symptoms

- Vital Signs every 4 hours
- Support breastfeeding
- Mother’s hand and breast hygiene
- Mother to wear a mask during breast feeding
- Plan for early discharge of mother and
baby if well
- Provide instructions for follow-up
Mother COVID-19 Mother COVID-19 positive

negative Neonate
COVID-19 test expected
to be negative
- Maintain Contact & Droplet precautions till -Isolation of both in a single room
other infectious causes of mother’s symptom has - Breastfeeding is allowed
been ruled out - Aim for 2 meter separation when not
- Routine Newborn care & Discharge planning providing direct care for baby
Figure 1. Algorithm For Handling a Healthy Neonate Born to Mother with Confirmed or Suspected
COVID-19 Who is Able to Look after Neonate
19
3. Guidelines for Pediatric Otolaryngologic Practice in
COVID-19 Positive Patients
3.1. Introduction
Recommendations herein have been made to ensure that the risk of
spread of the life threatening COVID19 infection is minimized among patients, families
and staff. They are also guided by the current knowledge of Covid-19 characteristics in
the paediatric population, namely that 13% of infected children are asymptomatic and
those symptomatic infected children have mild symptoms and that children may play a
major role in community-based viral transmission including faecal-oral transmission.
3.2. Management of elective and semi-elective paediatric out-patient

clinic and surgery
• The majority of paediatric ENT conditions will not result in serious harm or life
threatening situations over a period of 3 months, therefore operating and face-to-face
clinics must cease to prevent harm.
• There is recognition that a small amount of paediatric ENT pathology may rarely pose
a risk to life or cause serious harm to health, including rapidly enlarging neck
masses. These conditions must be recognised and treated.
• Adenotonsillectomy should be delayed unless despite maximal medical treatment,
delaying surgery would result in irreversible cardiopulmonary complications or
necessitate endotracheal intubation.
• The chosen technique for Adenotonsillectomy should depend on available expertise.
In the absence of any evidence that intracapsular tonsillectomy causes any increase
in aerosolisation over conventional dissection tonsillectomy, it would be the
preferred method to adopt due to the considerably reduced incidence of secondary
haemorrhage.
• Full AGP-PPE precautions should be taken during surgery.
3.3. Management of paediatric otolaryngological emergencies

Foreign bodies
• Retained button batteries remain an absolute emergency with respect to removal.
• Ingested foreign bodies causing absolute dysphagia will require removal.
20
• Otherwise, foreign bodies in the ear, nose and throat should be treated conservatively
unless there is significant risk to the airway or may cause long term sequelae if
removal is delayed (e.g. sharp objects).
• There will be many children who develop a cough and have a soft history of “playing
with small toy parts/food etc”. Unless they have stridor, dyspnoea or localizing signs
these should be observed and the CXR repeated. If available, a local CT scan may
help differentiate foreign body from other pathologies.
Periorbital abscess
Where vision is at risk, and conservative measures have failed, an external approach is
recommended.
Fractured nose
In the absence of a nasal septal haematoma, it is recommended that manipulation of
fractured nasal bones should not be carried out at the present time.
Acute mastoiditis
• Acute mastoiditis should be managed medically, and if appropriate by needle
aspiration of a subperiosteal abscess and a CT scan acquired only if symptoms
progress despite conservative management.
• A ventilation tube should not be used to manage intratemporal complications.
• If surgery is required due to life-threatening complications, it should be carried out in
line with the guidelines using curettage instead of drilling if possible.
Neck abscess
• Infective neck masses should be managed as outpatients as far as it is possible to.
• Progressively enlarging cervical or retropharyngeal collections may require surgical
treatment with full PPE.
3.4. Management of children with tracheostomy

• In line with ENTUK guidance, elective tracheostomy should be avoided at this time.
• Unavoidable tracheostomy should be carried out with full PPE using a cuffed un
fenestrated tracheostomy tube.
• Tracheostomy tube changes should be minimized.
• Tracheostomy training of parents of children who underwent tracheostomy prior to
Covid-19 should have their training accelerated to permit discharge as soon as it is
21
safe to do so.
3.5. Sick neonates

All sick neonates will be managed in neonatal intensive care unit (NICU).
3.6. Treatment
Covid-19 disease is a new issue. Little is based on high-level evidence. Pediatric
experience and evidence are even less. Many pediatric recommendations are based on
indirect evidence.
A. Non-specific therapy
• Isolation, rest and diet (as appropriate for age and tolerated).
• Nasogastric feeding should be initiated in those not tolerating oral feeds after 24h of
admission.
• I.V. fluid therapy for patients hospitalized with severe disease and those with
dehydration or intolerance to oral fluids
• Patients should be kept normally hydrated. Both overhydration and
dehydration should be avoided.
• Serum electrolytes & fluid balance should be monitored at least daily in all
patients receiving IV fluids.
• An initial prescription of 70% of normal maintenance is appropriate for most
patients provided that dehydration is corrected (deficit is added), losses due to
fever are accounted for and the patient is not accumulating a negative balance.
• Saline: glucose 1:1 with 20 mEq/L potassium is initially recommended when
electrolytes are normal and the patient is passing urine. Blood glucose should
be kept in the normal range & not exceeding 180-200 mg/dL.
• Significant hypoalbuminemia (<3g/dL) should be corrected with 0.5-1g/kg of
albumin (max. 20g).
Symptomatic treatment
Paracetamol is recommended for fever and pain (15 mg/kg/6h). Iboprufen may be added
with caution (max. 10 mg/kg/8h) if paracetamol is not adequate.
B. Assess/ monitor severity criteria
• General: lethargy, unconsciousness, convulsions or inability to drink/ breastfeed.
• Respiratory distress: tachypnea, retractions or grunting (Table 3)
22
• Hypoxemia: SpO2 <94% by pulse-oximeter in room air
• Severe or rapidly progressive pulmonary infiltrates on imaging (50% in 24-
48hrs)
• Other organ dysfunction (shock, heart failure, AKI, etc)
N.B. Patients with hypoxemia despite oxygen therapy, severe or increasing
respiratory distress, respiratory exhaustion, CO2 retention or other organ failure
should be managed in the ICU, Table 3.
Table 3. Evaluation of Respiratory distress: tachypnea, retractions or grunting
Age group Tachypnea limit (RR equal or above)
< 2 Mo 60/min
2 – <12 Mo 50/min
1 – <5y 40/min
5y & above 30/min
C. Respiratory support
Oxygen
• All patients with dyspnea, respiratory distress, hypoxemia or hemodynamic
compromise must receive oxygen to maintain SpO2≥94%
• Oxygen by face mask or hood is preferred to nasal cannula when feasible (Nasal
cannula is associated with higher expired air dispersion; i.e. risk of aerosolizing
virus)
Nebulization
Not routine and a highly aerosolizing procedure. To be used only when there is
definite indication eg bronchospasm
Mechanical ventilation
For respiratory failure (see below)
D. Antimalarial and Antiviral therapy (Refer to Section 14 for further guidance on
drug dosing and monitoring recommendations)
Despite limited evidence, hydroxychloroquine or one of the antiviral agents should be
used in patients requiring hospitalization
Hydroxychloroquine
6.5-10 mg/Kg (max. 400 mg) hydroxychloroquine sulfate
Given every 12 h in the first day; then given daily in 2 divided doses
23
Duration 5 days. May be extended in those with ongoing need for M.V. &
immunocompromised patients. Given with food or milk. May be dissolved & given
by NG tube.
Contraindicated in G6PD deficiency, QTc >500ms (do ECG before), arrhythmias,
liver disease, advanced renal impairment and myasthenia. May cause/ increase
seizures.
Antiviral agents
Lopinavir-Ritonavir
Dosing (orally twice daily)
14 d age - <15kg: (16 mg+4mg)/kg/ dose
15-25 kg: (200 mg+50 mg)/ dose
26-35 kg: (300 mg+75 mg)/ dose
>35 kg: (400 mg+100 mg)/ dose
Duration 5 days. May be extended in those with ongoing need for M.V. &
immunocompromised patients . Consider drug interactions (see Drug-interaction
section)
Remdesivir:
It needs to be administered as early as possible in the infection cycle.
5 mg/Kg (max. 200 mg) IV on day 1; then
2.5 mg/Kg (max. 100 mg) IV every 24h
Contraindications: Evidence of Multi-organ failure, pressor requirement, ALT levels
> 5 X upper limit, Cr Clearance <30 mL/min or need for dialysis
Favipiravir
Safety and efficacy data regarding the dosing recommendation in children were not
published. Manufacturer label states that it has not been administered to children. In
animal studies, death cases, abnormal gait, atrophy and vacuolation of skeletal
muscular fiber, degeneration/necrosis/mineralization of papillary muscle have been
reported, Table 4. For Children weighing > 55 kg see drug section for adult
dosing used in COVID-19
24
Table 4. Weight-band Dosing Table for Faripiravir in Children (age ≥ 1 y, weight ≥
10 kg) Infected with Ebola Virus Disease (Safety and efficacy not established)
Day 1 Days 2-10
H0 (First H8 H16
Dose)
10-15 kg 500 mg 500 mg 200 mg 200 mg three times
daily
16-21 kg 800 mg 800 mg 400 mg 400 mg twice daily
H=Hour
Oseltamivir
Given if influenza is suspected. Has been used despite some negative studies in Covid19.
Children and Adolescents: For 5 days
≤15 kg: Oral: 30 mg twice daily.
>15 to 23 kg: Oral: 45 mg twice daily.
>40 kg: Oral: 75 mg twice daily.
Infants ≤8 months: Oral: 3 mg/kg/dose twice daily (AAP 2019; CDC 2019; IDSA
[Uyeki 2019]; IDSA/PIDS [Bradley 2011]).
Infants ≥9 months: Oral: 3.5 mg/kg/dose twice daily (AAP 2019; IDSA [Uyeki 2019]);
some experts still recommend 3 mg/kg/dose twice daily (CDC 2019; IDSA [Uyeki
2019]).
Azithromycin
Given in a dose of 12 mg/kg/day (max. 500mg) for 5 days
May also have an immunomodulatory role
Other antibacterial antibiotics
Not routinely indicated
Use for prevention/ treatment when bacterial infection is possible or for prevention of
secondary bacterial infection in the ICU
25
E. Therapies targeting immune response
Corticosteroids
Hydrocortisone in those with volume refractory shock
(50-100 mg/m2 initial dose then 50-100 mg/m2/day divided q6h)
Methylprednisolone:
For those with cytokine storm if Tocilizumab is not available
May be started in those with severe progressive lung disease & rising inflammatory
markers 2mg/Kg/day for a maximum of 5 days
Tocilizumab:
Monoclonal antibody to IL-6, used in those with cytokine storm & can be considered
for those with partial improvement on steroids with high inflammatory markers
Dose: 12 mg/Kg in those weighing <30 Kg, 8 mg/kg (max. 400 mg) in larger patients
Given IV over 1 hour and may be repeated if response is inadequate after 8-12 h
(max. 3 doses)
CVVH
In those with AKI and MODS, can have the additional benefit of cytokine clearance
Convalescent antibody-rich plasma
Obtained from recovered subjects who are HBsAg, HCV & HIV negative and ABO-
compatible has been used in limited series with some success in severe cases not
responding to antiviral therapy
F. Multisystem support
• Hemodynamic support
• Shock: normal saline 10 mL/Kg bolus, reassess before repeating
• Early use of vasopressor support in volume-refractory cases:
Noradrenaline 100ng/kg/min, titrated to response, If not available,
dopamine 10μg/Kg/min
• Blood transfusion to a relatively higher target Hb (eg 10g/dL) may be
beneficial in those with refractory shock &/or hypoxemia
• Patients with myocardial dysfunction (high filling pressures, impaired
contractility) and evidence of low cardiac output require inotropic support
Dobutamine or Milrinone. Levosimendan may be used in refractory cases.
Caution of arrhythmias with adrenaline in those with myocarditis
26
• Control of seizures & management of coma
• Control of metabolic disturbances
• Management of AKI
• Fluid balance
• Correction of electrolyte/ acid-base disturbances
• Review/ adjustment of medication doses
• Furosemide (2mg/Kg followed by 0.5-1 mg/kg/h infusion) may be used for
oliguric patients so long there is a response
• When renal replacement is needed, CVVH (with systemic anticoagulation
unless contraindicated) is the treatment of choice if available. PD is also
possible. Few patients will be fit for HD & transfer to the dialysis unit may not
be feasible.
• Hematological support
Anticoagulation
May be considered for those with D-dimer >2 or pulmonary wedge infarcts on
imaging.
Low molecular weight heparin (enoxaparine) 1mg/Kg/12 h or unfractionated heparin
guided by PTT may be used unless contraindicated.
G. Mechanical ventilation:
Non-invasive ventilation
Non-invasive ventilation can be associated with increased virus dissemination. A
short trial may be acceptable in those with severe RD/ cannot maintain adequate
oxygenation and are otherwise suitable for NIV (adequate consciousness, adequate
airway, adequate drive and adequate hemodynamics). Patients should be in a single
room. Patients should be intubated if there is no clear improvement on NIV. Avoid
prolonged trials.
Indications of mechanical ventilation:
- Respiratory exhaustion
- Refractory severe hypoxemia (PaO2 <50-60 mmHg) on maximal oxygen therapy
- Progressive CO2 retention with academia
- Failure of NIV
- Non-respiratory indications especially refractory hemodynamic compromise and
Deep coma
27
Intubation
• Emergency intubations on the ward may increase the risk of exposure. Patients
should ideally be admitted to the PICU before the need arises.
• Bagging, especially before intubation, can increase the risk of exposure.
Bagging should be minimized or avoided if possible both before & after
intubation. Have ventilator ready to enable immediate connection once
intubated.
• Use filters between the bag valve & ET tube, and on the ventilator circuit.
Ensure the absence of leaks on patient circuit
• Ensure full appropriate PPE and minimum personnel necessary for intubation
• Rapid sequence intubation with sedation & paralysis unless contraindicated.
Avoid awake intubations:
Use ketamine (1-2 mg/Kg) or propofol (2-4 mg/Kg; only in hemodynamically
stable patients). Premedicate with atropine (0.02 mg/Kg) and paralyze with
atracurium (0.6 mg/kg)
• Used cuffed ET tubes when available and inflate as soon as possible after
intubation
• Minimize/ avoid open suction. A closed system is recommended
Invasive mechanical ventilation
NOTE:
• Hypoxemia and extent of pulmonary lesions do not correlate well.
• Patients have variable degrees of lung compliance, V/Q mismatching &
recruitability. Not all initially have severe ARDS pathology.
• Treatment therefore should be individualized with monitoring responses and
adjustment.
• Pressure control, volume control & dual control modes are all acceptable.
Initial suggestions are as follows
• Patients should be initially well sedated & possibly paralyzed
• Initial FiO2 should be high (1.0 in most patients) and decreased as soon as
feasible. Monitor oxygenation & arterial/ inspired oxygen ratio (either
PaO2/FiO2 or SpO2/FiO2 is acceptable)
28
Gas exchange Mild Moderate Severe
impairment
PaO2/FiO2 <300 <200 <100
SpO2/FiO2 <235 <181 <118
• Initially use the normal rate for age (40 in infants, 30 in children, 20-25 in
older children) and an i/e ratio of 1:2. Longer Ti may be used if needed,
up to 1:1.
• Attempt to start with ‘normal’ PEEP eg 5cmH2O; and
- Start with a normal tidal volume (6-8 mL/Kg), provided PIP ≤30cmH20 and
∆P (above PEEP) up to 15-20cmH2O
- Using pressure control, aim for adequate tidal volume & oxygenation with
pressures within above limits
• Patients with poor lung compliance and low arterial/ inspired ratios (severe
ARDS pathology) would not be able to achieve adequate tidal volume &
oxygenation within these PIP & ∆P values. These are likely to benefit from a
high PEEP strategy (from 8-10 cmH2O) and prone ventilation, with possibly
lower tidal volumes & permissive hypercapnia
• Benefit from the use of further PEEP must be demonstrated in terms of
improved oxygenation, otherwise it may cause excessive lung strain even
with a ‘normal’ tidal volume
• High frequency ventilation may be considered for patients with poor
oxygenation (hypoxemia or persistent need for toxic FiO2) despite high PEEP
• ECMO support, if available, may be considered for those failing MV
3.6.Tips for families facing long periods of time isolated at home during
the COVID-19 Pandemic
1. Prevent boredom: Keep kids busy with a healthy and productive schedule at
home.
2. Address fears: Talk with children about any frightening news they hear.
3. Use time-outs: This discipline tool works best by warning children they will get
a time-out if they don't stop. (1 minute per year of age is a good guide).
4. Redirect bad behavior: Children need some guidance. Find something else for
your child to do.
29
5. Know when not to respond. As long as your child isn't doing something
dangerous and gets plenty of attention for good behavior, ignoring bad behavior can
be an effective way of stopping it.
6. Praise success. Notice good behavior and point it out,
7. Allow time for attention. When parents are trying to work at home with children
who are out of school or child care, this can be tough.
8. Avoid physical punishment. Physical punishment can increase aggression , fails
to teach children to practice self-control and may take away a child's sense of safety
and security at home, which are especially needed now.
9. Take care of yourself. physically: eat healthy, exercise and get enough sleep. Find
ways to decompress and take breaks. If more than one parent is home, take turns
watching the children if possible.
10. Remember to take a breath. In addition to reaching out to others for help, try to
take just a few seconds to ask :
• Does the problem represent an immediate danger?
• How will I feel about this problem tomorrow?
• Is this situation permanent?
In many cases, the answers will deflate the panic and the impulse to lash out
physically or verbally at children.
30
4. Guidelines of Kidney Transplantation during the COVID-19
Pandemic
4.1. Introduction
The WHO announced COVID-19 as a pandemic on March 19 with rapidly increasing
number of cases all over the world. The pressure on the health care system is very high
in several countries and increasing numbers of infected health care staff are being
reported. Many countries have imposed major restrictions on meetings, travel, and
everyday life. This is likely to impact greatly on the transplant activity in many other
parts of the world. By analogy with other infectious diseases, it is considered that kidney
transplant patients under immunosuppression are at higher risk of poor outcomes,
although this has not been proven to date. It is important to note that information about
this disease and our understanding of this virus and its impact on transplantation is
evolving rapidly so the guidance may change over time.
Mortality appears to be age dependent, with the highest rates among older adults (Age
50-59: 1.3%, 60-69: 3.6%, 70-79: 8%, 80+: 14.8%). Although many patients had co-
morbidities in the reported series, data on transplant patients is limited. Nevertheless the
lymphocyte count was lower in those who required ICU care. It is not possible to tell if
lymphopenia was a manifestation of a more severe form of disease, or if it predisposed
to severe disease. Many transplant recipients have medication-induced lymphopenia.
Particularly close attention should be paid to transplant patients with suspected or
confirmed COVID-19 infection who are lymphopenic.
4.2. Recommendations
Transplant program
• All transplant-related teams should develop plans to reduce burden on the
healthcare system and mitigate against interruption in care of transplant patients.
• Temporary suspension of the living-donor kidney transplant programs should be
considered when donation can safely be deferred to a later date.
• If transplantation is required as a life-saving procedure, it can be conducted with
appropriate assessment of infection donor and recipient and with appropriate
informed consent.
31
• If donors or recipients are suspicious, SARS-CoV-2 should be excluded.
Transplant centres
• Outpatient clinic visits that are not critical should be either deferred or substituted
with telemedicine.
• Visitors should be restricted as much as possible to transplant floors.
• Specify team members who may be impacted with suspicious transplant patients
• Determine who can work remotely and ensure they have the resources to do so.
• Develop messaging for candidates and recipients about how and when to contact
the transplant centre in case of illness.
• Develop guidance for candidates and recipients about risk mitigation, including
limiting exposure to large crowds, hand hygiene and avoidance of sick exposures.
• Staff and facility should be prepared to receive suspicious patients.
• They should develop guidance for which suspicious transplant recipients need
evaluation, testing and management by the transplant centre vs. which can remain
at home with close remote follow-up.
• Staff with respiratory symptoms should stay at home (National policies should be
applied).
• Testing of staff should be done according to national and local guidelines
• Prevention policies and procedures: National, local and institutional guidelines
should be followed. .
Transplant donors
• In case of diagnosis of COVID-19 infection, donor must be excluded from
donation at least three months, deferral can be considered unless the need for
donation is urgent when individual consideration should be made with at least 28
days lapse.
• In case of close contact with a person diagnosed with SARS-CoV-2 infection, the
donor shall be excluded from donation for at least 28 days. Donor should be
closely monitored for the presence of COVID-19.
• In case of travel to high risk areas for COVID-19 infection (as defined by health
authorities) or being a close contact with person travelling from such an area,
donor shall be excluded from donation for at least 28 days.
32
• If the patient’s need for transplant is urgent, SARS-CoV-2 infection must be
excluded completely according to MOH criteria for both donor and recipient.
• Donors within 28 days before donation should practice good hygiene (The WHO
recommendations) and avoid crowded places and large group gatherings. .
Transplant Recipients
• Transplant recipients should avoid travel.
• Transplant recipients with higher incidence of infection:
1. In contact with COVID-19 infected people or within 14 days prior to the
onset of the disease
2. History of travel within 14 days
3. In contact with patients who have fever or respiratory symptoms.
• They should avoid elective clinic visits.
• Suspicious transplant recipients should be instructed to call the transplant centre
and avoid presenting to the clinic without notifying it in advance to avoid
inadvertent exposures.
• They should be examined clinically, laboratory and radiologically according to
our national policies, to exclude or confirm COVID-19 virus infection.
• Algorithm for modulation of immunosuppressive medication for kidney transplant
during the COVID-19 pandemic should be followed, Figure 2.
33
Figure 2. Modulation of Immunosuppressive Medication for Kidney Transplant during the COVID-19 Pandemic
34
4.3. Management of immunosuppressive medication for kidney transplant
patients during the COVID-19 pandemic
A. Asymptomatic patients, no knowledge of COVID-19 status (ambulatory, stable
patients):
No change of immunosuppressive medications
B. Mild disease (the patient has only mild upper respiratory, temperature < 38°C, and
does not refer symptoms suggestive of COVID-19 pneumonia such as dyspnea,
persistent chest pain and intensive cough; oxygen saturation in room air is >95%,
respiratory rate < 25/min); no evidence of pneumonia on CT:
• If patient is on triple therapy: Stop MPA/AZA/mTORi, maintain on dual therapy
CNI-steroids.
• If patient is on dual therapy: continue dual therapy. If dual therapy is a steroid-free
regimen: for CNI + MPA/mTORi, consider replacing MPA/mTORi with low dose
steroids. If on MPA+mTORi, consider replacing MPA or mTORi with low-dose
steroids.
• Consider CNI dose reduction (to the lower bound of the therapeutic range according
to the immunological risk) if there is no clear improvement over the first 3-5 days.
C. Patients with evidence of mild COVID-19 pneumonia (oxygen saturation 94-95% in

room air, respiratory rate 25-29/min; or suspect lesions on CT scan):
a. High risk patient: (age 70+, or because of comorbidities or risk factors diabetes,
cardiac or pulmonary disease, heavy smoking, BMI > 30 kg/m2, eGFR <30
ml/min/1.73m2, lymphocyte depletion therapy within previous 3-6 months):
• Stop MPA/AZA/mTOR, stop CNI, increase (or start) steroids 15-25 mg/day
b. Not high-risk patient (as defined above):

• Stop MPA/AZA/mTOR, maintain on dual therapy CNI-steroids. Always reduce CNI
levels to target CsA: 50±15 ng/ml, TAC: 3±1 ng/ml. Continue steroids in
maintenance dose.
c. If starting anti-retroviral (Lopinavir/Ritonavir) treatment is thought to be life

saving: stop CNI (to avoid severe drug interaction) , and monitor as shown below.
35
D. Patients with more severe COVID-19 pneumonia (oxygen saturation <94% in room
air, respiratory rate ≥30/min), unstable or deteriorating course or requiring non-
invasive ventilation or transfer to the intensive care unit (with or without
mechanical ventilation):
• Discontinue all IS drugs, if possible; increase/start steroids at 15-25 mg/day (or
higher according to local practice). Carefully consider to continue with low dose CNI
in patients with higher risk of rejection.
When to resume immunosuppressive therapy?
A proposed approach is to resume the calcineurin inhibitor at half of the previous dosage,
starting at least 30 days after clinical resolution (apyrexial patient, no need for oxygen
therapy, negative CT chest) and after two negative swabs (one at discharge and one at 3
days), with the aim of gradually reaching a level of 3-5 ng/ml of tacrolimus and 200-300
ng/ml of cyclosporine at the second hour. Resumption of full‐dose calcineurin inhibitor
dosage and maintenance of the prednisolone (based on clinical judgement) after 15 days
free of symptoms and an additional negative swab. Case-by-case evaluation of re-
initiation of MMF, azathioprine and m-TOR inhibitors.15
Drug interactions between chloroquine/hydroxychloroquine, anti-retroviral drugs,
and IS drugs:
1. There is a possible increase in the exposure of cyclosporine, tacrolimus, and mTOR
inhibitors with chloroquine/hydroxychloroquine.. As chloroquine/hydroxychloroquine
are given for only 5 days, it is advised, to follow the trough levels of cyclosporine,
tacrolimus, and mTOR inhibitors in this setting.16
2. Patients starting anti-retroviral drugs that contain ritonavir or cobicistat must stop
mTOR inhibitors and CNIs. If the aim is to continue tacrolimus, it should be administered
only when blood levels are < 5 ng/ml, and the dose should not exceed 0.5 mg (overall
dose reduction 1/5 or lower). Cyclosporine should be given only when levels are below
50 ng/mL (overall dose reduction 1/5 or lower, administered once a day).17
3. Administration of azithromycin should be accompanied with monitoring of
cyclosporine levels closely. There is a possibility of rise cyclosporine level. AS,
azithromycin may cause the increased cyclosporine concentrations through glycoprotein
inhibition and/or competition for biliary excretion.18
36
Currently recommended medications for COVID-19
Drug Dose Mechanism Rationale for Notable Other
use Adverse considerations
Reaction
s
Hydroxychloro 400mg PO -Prevents -In-vitro data -QTc -There is a
quine q12h x 24h acidification shows prolonga theoretical
(HCQ)* followed by of potent SARS- tion potential for
200mg endosomes COV-2 -Rash an increase in
q12h x 4 interrupting inhibition and - hydroxychloro
days for a 5 cellular early Retinopa quine levels
day total functions clinical data thy is when used
duration and shows rare with
then replication possible (Baseline atazanavir
reassess - Prevents benefit eye exam therefore
viral entry -HCQ was is not monitor for
via ACE2 found more required possible QTc
binding potent than for prolongation
-Reduction of chloroquine use for - For patients
viral in inhibiting COVID- with
infectivity SARS-CoV-2 19) NG/OG/NT
- in vitro hydroxychloro
Immunomod quine can be
ulator crushed for
enteral
administration
-Therapy can
be extended
past 5 days
based on
patient’s
clinical
response, but
should not
exceed 10 total
days
IMMUNOMODULATING AGENTS
Tocilizumab* 8mg/kg IV Monoclonal -IL-6 receptor - -The use of
x 1 dose antibody to antagonist Headach IL-6 levels
(actual IL6 may attenuate e should NOT
body receptor cytokine - guide decision
weight); release in Elevated to
dose max patients with liver administer
800 mg) severe disease Enzymes tocilizumab at
-Retrospective -Infusion this time
data reactions - Additional
suggest (e.g. doses not
possible flushing, indicated at
37
benefit chills) this time
(clinical trials
ongoing)
Medications which may be available through Clinical Trials
Remdesevir* Clinical Viral RNA In-vitro data -Nausea, -As of 3/22/20
Trial dependent reveals vomiting, remdesivir is
dosing RNA potent SARS- - available
polymerase COV-2 Elevated through
inhibitor inhibition and liver clinical trials
early enzymes only and not
clinical data -Rectal through
shows bleeding compassionate
possible use except for
benefit pregnant
patients and
those < 18
years of age
still have
the option for
compassionate
use program
-Gilead is
working on an
expanded
access
program
Medications which may be available through Clinical Trials
Sarulimab 400mg/100 Monoclonal IL-6 receptor- -Available
mg PO antibody to antagonist Elevated through
q24h x 5 IL6 may attenuateliver clinical trial
days then receptor cytokine enzymes only at this
reassess release in - time
patients withLeukope
severe disease
nia
-Infusion
reactions
(e.g.
flushing,
chills
Medications NOT currently recommended as first line for COVID-19
Drug Dose Mechanism Rationale for Rationale for NOT
possible including as first line
efficacy agent
Lopinavir/ 400mg Viral In-vitro data Limited availability, poor
Ritonavir* (2-200mg protease reveals potent tolerability (such as GI
caps) PO inhibitor SARS-COV-2 sideeffects) and recent
q24h x 5 inhibition data demonstrated
days then questionable clinical
38
re-assess efficacy
Atazanavir 500 mg x 1, Viral -More potent -Mild indirect
NO LONGER followed by protease binding to the hyperbilirubinemia is
RECOMMEN 250 mg inhibitor virus common and not
DED q24h x 4 compared to indicative of hepatic
AS FIRST days other dysfunction
LINE protease -CYP enzyme inhibitor
due to updated inhibitors in (3A4, 2C8)
Lopinavir vitro (lower monitor/discuss with
/ritonavir than pharmacy potential for
data19 lopinavir) drug-drug interactions
-Drug more -For patients with
widely NG/OG/NJ open capsules
available than for enteral administration
other PI’s -Atazanavir needs an
including acidic environment for
lopinavir/rito absorption and therefore
navir and antacids, H2 blockers,
better proton pump inhibitors
tolerated (PPIs) should be avoided.
If these agents must
be given the
administration should be
separated as below:
1.Atazanavir should be
given 2 hours before or 1
hour after antacids
2.Atazanavir should be
given at the same time as
the H2 blocker or the
atazanavir should be
given 10 hours after or 2
hours before the H2
blocker
-For PPIs avoid
concomitant use
Azithromycin* 500 mg x 1, Not well In a small -Very limited data on use
followed by defined; study, of azithromycin alone or
250 mg possible combination in combination with other
q24h x 4 immunomod of HCQ and agents
days ulator azithromycin 1.Gautret, et al. study is
was associated limited by small sample
with size (only 6 patients
significant a received HCQ &
reduction in azithromycin
SARSCoV- combination) and those
2 viral load patients had lower viral
loads than other included
patients
39
-Combination of HCQ
and azithromycin and
atazanavir can increase
the risk for QTc
prolongation
Darunavir/ 800 mg Viral In-vitro data Decreased binding to viral
Cobicistat23 /150 mg protease shows SARS- protease compared to
PO q24h inhibitor COV-2 atazanavir. No clinical
x 5 days inhibition data at this time
Ribavirin N/A Viral RNA In vitro data -Limited evidence for
polymerase for use in SARS-CoV-2 and toxicity
inhibitor and SARS-CoV risk outweighs benefit of
inhibition of and MERS- use
elongation of CoV -Typically used with
RNA indicates interferon
fragments possible -Studied in patients with
activity other coronaviruses with
mixed results
Oseltamivir* N/A Inhibits Activity -No current data to
influenza against support use of this drug.
virus influenza -Additionally, SARS-CoV-
neuraminidas virus 2 does not use
e neuraminidase in
blocking viral the replication cycle so
release mechanistically there
would be no
benefit
Nitazoxanide N/A Augments In-vitro data No clinical data available
host reveals SARS-
antiviral COV-2
response inhibition
Interferonbeta N/A Immunomod -Possible -Limited data with SARS-
ulator activity CoV-2, toxicity risk
against SARS- outweighs benefit of use
CoV and -Have been studied for
MERS-CoV patients with other
-Typically coronaviruses with mixed
used in results
combination -Not interferon-alpha or
with ribavirin interferon-gamma
Corticosteroid If Inhibit May be -Lack of effectiveness and
s indicated production helpful in potential harm shown in
per of attenuating literature specifically
protocol: inflammatory cytokine inhibition of viral
Methylpred cytokines that release in clearance in severe
nisol regulate patients with influenza and SARS,
one neutrophil severe disease though possible benefit
40mg and T-cell with critically ill
q8hr IV responses COVID19 patients 35
for three leading -May be considered for
40
days, then to immune use by critical care team
re-assess suppression for salvage therapy
-Corticosteroids should be
used if clinically indicated
as part of standard of care
such as for an asthma or
COPD exacerbation, or
shock with history of
chronic steroid use
Intravenous N/A Neutralizing -May have Drug is on critical
immunoglobuli antibodies both antiviral national shortage and has
n against and an unclear role as current
(IVIG the virus immunomodu preparations will not
latory contain antibodies against
effects SARS-CoV-2 at this time
-A recent
observational
study
reported
clinical and
radiographic
improvement
in 3 patients
who
received high
dose IVIG at
time of
respiratory
distress
Baricitinib N/A Janus Kinase May have -Not available for off label
(JAK) targeted use
inhibitor antiviral and -No clinical data available
binding immunomodu -Risk of severe infections
cyclin G - latory with use
associated effect with less References:
kinase,may side-effects at
inhibit an effective
viralentry via dose than
endocytosis other JAK
inhibitors
* Refer to Section 14 for further guidance on drug dosing and monitoring recommendations
41
5. Guidelines for Management of COVID-19 in Kidney Failure
5.1. Suspected Cases

Take an electrolyte panel to see whether dialysis is immediately needed, or that this can be
postponed until the results of the nasopharyngeal swab polymerase chain reaction and
computer-aided tomography of the chest are known.1
• Early recognition and isolation of individuals with respiratory infection.
• Facilities should implement sick leave policies that are non-punitive, flexible and
consistent with public health policies that allow ill healthcare personnel (HCP) to stay
home. HCP should be reminded to not report to work when they are ill.
• Facilities should identify patients with signs and symptoms of respiratory infection
(e.g., fever, cough) before they enter the treatment area.
• Instruct patients to call ahead to report fever or respiratory symptoms so the facility
can be prepared for their arrival or triage them to a more appropriate setting (e.g., an
acute care hospital).
• Patients should inform staff of fever or respiratory symptoms immediately upon
arrival at the facility (e.g., when they check in at the registration desk).
• Patients with symptoms of a respiratory infection should put on a facemask at check-
in and keep it on until they leave the facility.
• Facilities should provide patients and HCP with instructions) about hand hygiene,
respiratory hygiene, and cough etiquette.
• Instructions should include how to use facemasks, how to use tissues to cover nose
and mouth when coughing or sneezing, how to dispose of tissues and contaminated
items in waste receptacles, and how and when to perform hand hygiene.
• Post signs at clinic entrances with instructions for patients with fever or symptoms of
respiratory infection to alert staff so appropriate precautions can be implemented.
• Facilities should have supplies positioned close to dialysis chairs and nursing stations
to ensure adherence to hand and respiratory hygiene, and cough etiquette. These
include tissues and no-touch receptacles for disposal of tissues and hand hygiene
supplies (e.g., alcohol-based hand sanitizer)
42
• Patient placement: Facilities should have space in waiting areas for ill patients to sit
separated from other patients by at least 6 feet.
• Medically stable patients might opt to wait in a personal vehicle or outside the
healthcare facility where they can be contacted by mobile phone when it is their turn
to be seen.
• Patients with respiratory symptoms should be brought back to an appropriate
treatment area as soon as possible in order to minimize time in waiting areas.
• Facilities should maintain at least 6 feet of separation between masked, symptomatic
patients and other patients during dialysis treatment. Ideally, symptomatic patients
would be dialyzed in a separate room (if available) with the door closed.
• If a separate room is not available, the masked patient should be treated at a corner or
end-of-row station, away from the main flow of traffic (if available). The patient
should be separated by at least 6 feet from the nearest patient (in all directions).
• Health care workers should be trained for dealing with all cases under PPE according
to individual case scenario.
• When COVID-19 is suspected or confirmed in a patient receiving hemodialysis
at the facility, the following additional measures apply:
• The health department should be notified about the patient.
• HCP should follow the Interim Infection Prevention and Control
Recommendations for Patients with Confirmed Coronavirus Disease 2019
(COVID-19) or Persons Under Investigation for COVID-19 in Healthcare
Settings.
• This includes recommendations on PPE. Routine cleaning and disinfection are
appropriate for COVID-19 in dialysis settings. Any surface, supplies, or
equipment (e.g., dialysis machine) located within 6 feet of symptomatic patients
should be disinfected or discarded.
• Minimize patient exposure
o Encourage patients, and their care giver if needed, to use their own transport,
and to travel alone to the dialysis unit when possible.
o Minimize time in the waiting area by:
43
Careful scheduling
Encouraging patients not to arrive early
Texting patients when you are ready to see them, so that they can wait outside,
for example, in their car.
o If a patient is COVID-19 negative and has symptoms, ensure that other
explanations for the symptoms have been considered and treated.
o At subsequent assessment, retest the patient if there is still a clinical suspicion
of COVID-19.
o Outlining restrictions to the dialysis unit to those staff and visitors essential to
the delivery of the service
Key notes
• Educate your patient how to stay safe at home.
• Educate patients relatives how to protect themselves from COVI-19.
• Encourage patients not to use public transportation if possible? If not, use all protection
tools e.g face mask and gloves.
• Patients entrance and exit should not be in groups leaving about 6 feet (1.8 m) spacing in
between.
• Meals are not allowed on session, only allow controlled snack e.g small candy to prevent
hypoglycaemia.
• Washing hands upon entry and before leaving the center.
• Patients never share thier personal belongings.
• On praying do not use carpets, only pray while seated.
• Pass route for entering hospital and dialysis unit: -
-The pick-up and drop-off should not be shared with other dialysis patients.
-Entering and exiting with other patients at the same time should be avoided.
-The route, mode and time of transport of dialysis personnel should be fixed.
• Management Protocol for Dialysis Patients Suspected to have COVID-19 Infection is

presented in Figure 3.
44
5.2. How should facilities monitor or restrict dialysis facility staff?
• The same screening performed for patients should be performed for facility staff
• Dialysis staff who have signs and symptoms of a respiratory infection should not report
to work. Facilities should implement sick leave policies that are nonpunitive, flexible
and consistent with public health policies that allow ill staff members to stay home.
• Any staff member that develops signs and symptoms of a respiratory infection, should:
• Immediately stop work (if working), put on a facemask, and self-isolate at home
• Inform the facility administrator, and collect information on individuals,
equipment, and locations the person came in contact with; and
• Contact and follow the local health department recommendations for next steps
(e.g., testing, locations for treatment).
• The medical waste from confirmed or suspected patients with COVID-19
infection should be considered as infectious medical wastes and disposed
accordingly.
• The health department should be notified in instances of suspected or confirmed COVID-
19 infection.
• All the family members living with dialysis patients must follow all the precautions and
regulations given to patients to prevent person-to-person and within family transmission
of the COVID-19, which include body temperature measurement, good personal
hygiene, handwashing, and prompt reporting of potentially sick people.
• Dialysis patients, who have a family member or caregiver subject to "basic quarantine",
can have dialysis as usual in accordance during the 14-day period.
• Once the family members or caregiver of dialysis patients have been converted to a
confirmed case, the patient's identity should be upgraded and treated in a designated area
with check for a confirmatory test for COVID 19.
5.3. HD prescriptions in regular HD patients
According to the Egyptian HD Guidelines
• All patients should receive their regular HD sessions in both duration and frequencies.
• It is advisable to use the High Flux dialysis Membranes.
45
• Always individualize therapy according to patient needs.
5.4. HD Modality
• Cytokine storm associated with elevated levels of IL-6, IL-18 and IFN gamma are
associated with more severe disease and higher mortality.
• Extracorporeal therapies using high volume hemofiltration or adsorption to decrease
cytokine levels may theoretically be expected to confer benefit.
5.5. Peritoneal Dialysis

• Acute PD
• Use of acute peritoneal dialysis can be lifesaving and should be used as and when
required and, in the setting, where hemodialysis facility is not available. Health care
worker should use all precautions while initiating acute PD and discard used
consumables properly.
5.6. AKI management with covid-19 positive patients
• Preliminary considerations
• Dialysis procedures, in chronic HD patients and in patients with AKI, are at risk of
transmission and dissemination of COVID-19 for multiple procedural and logistical
aspects
• Indications to start RRT are similar to other patients with AKI
• CRRT filter changes can be performed every 72 hours or at longer intervals per
institution protocols.
• After treatment, dialysis equipment should be cleaned with a disinfectant as per CDC
and manufacturer’s recommendations.
• The equipment should be disinfected before removed from the room.
• Some institutions make require additional cleaning before machine can be used for
another patient.
• All disposable RRT machine equipment (tubing/filter sets, CRRT solutions bags,
etc.) should be discarded as directed by hospital infection control & policy
46
5.7.CRRT and SLED in ICU American Society of Nephrology Release
Date: March 21, 2020
• The preferred modality for RRT in critically ill patients is CRRT or sustained low
efficiency dialysis (SLED) and other terminologies.
• In ICUs where ICU nurses are all trained and competent on the use of CRRT,
hemodialysis nurses do not need to have direct contact with patients, thereby limiting
healthcare staff exposure
• Patient fluid removal rate will depend on various factors, and may be regulated by ICU
physicians, if patients are undergoing CRRT or SLED.
• If patient surge overwhelms CRRT capacity at an institution, consideration should be
given to using CRRT machines for prolonged intermittent treatments (e.g. 10 hours
instead of continuous) with higher flow rates (e.g. 40 - 50 ml/kg/hour) and then using the
machine for another patient, after terminal cleaning. Institutional policies.
• For dialysis treatment of patients hospitalized in dedicated spaces or rooms, use of
monitors for continuous techniques (CRRT).
• Management modalities of the session defined by the Nephrologist based on the clinical
complexity.
• No contraindications to the use of intermittent or SLED techniques if the logistical
conditions allow it with the use of portable osmosis.
• Currently there is no scientific evidence of the need for dedicated dialysis monitors;
thorough cleaning / disinfection of the equipment at the end of the session
• CRRT
• CRRT is beneficial to maintain volume balance, hemodynamics, and to allow plenty
of nutritional support
• Improve the clearance efficiency of medium and small molecular toxins, maintain
body temperature
• CRRT is highly indicated in patients with AKI who is suspected to have high levels
of cytokines and hemodynamic instability.
47
• According to ERA/EDTA 2020
• Patients with COVID-19 are reported to have a high risk of thromboembolic events
and, therefore, several centers use higher dosages of thrombosis prophylaxis than
usual (often double-dose).
• SLED and IHD
• If CRRT is unavailable
• Theoretically use HDF with a dialyzer capable of removing cytokines identified by
Membrane SC values (SC of Myoglobin > 0.5)
• Use more prolonged sessions to overcome the continuous cytokine production
(balance between production and removal)
• Control of drug doses accordingly
• If HDF is not available, use SLED technique with the same dialysis membrane
above.
• In presence of our inability to obtain instantaneous monitoring of biological levels of
cytokines, the reasonable approach is to promote a nonspecific removal assuming
that those cytokines with the highest concentration will be removed in higher amount
5.8. CYTOKINES MOLECULAR WEIGHT

• IL-6 Homodimer 19-26 KD
• IL-7 Monomer 25 KD
• IL-8 Homodimer 16 KD
• IL-10 Homodimer 20.5 KD
• IL-11 Monomer 19 KD
• IL-12 Heterodimer 35 KD
• IL-16 Homotetramer 56 KD
• IL-17A 35 KD
• IL-18 Heterodimer 22.3 KD
• IL-19 Monomer 20.5 KD
• TNF-a Homotrimer 26 KD
48
5.9. Drug modification in patients on hemodialysis
N.B. Should be carried out in collaboration with clinical pharmacist
The components of these drugs are highly protein-bound; significant removal via dialysis
is not likely. Experimental COVID-19 drug therapies include hydroxychloroquine and
antivirals (lopinavir/ritonavir).
Refer to Section 14 for further guidance on drug dosing and monitoring
recommendations
49
Management Protocol for Dialysis Patients Suspected to have COVID-19 Infection
At Home In Triage
At Home
1. Complaining of Fever, Cough, Syspnea, sore throat or ILI.
‫ش‬2. In contact with COVID-19 infected people or within 14 days prior to the onset of the disease
3. History of travel within 14 days
4. In contact with patients who have fever or respiratory symptoms.
If the patient is suspicious. Proceed

for KFTs, ABG and clinical
assessment. If the patient is not
indicated for urgent dialysis postpone Yes No
dialysis until results are obtained
HRCT Chest & Chest Consultation
CT appearance CT appearance non- Normal

suggestive of suggestive of COVID-
COVID-19 19
Nasopharyngeal swab for Laboratory Tests suggestive of

PCR (NAT) COVID-19 (CRP, CBC, D-
dimer, Ferritin, Fibrinogen, TG,
Liver enzymes, & others)
Negative first sample or
waiting for results
Yes No
No Yes
Routine dialysis in isolation

Routine dialysis in zone last shift
isolation zone last shift
Repeat Repeat CT Chest after

Nasopharyngeal swab for 14 days of treatment
PCR (NAT) after 48 hours
Positiv Negative
Worsening Improving or
e Within Normal
50
Transfer to dialysis ward
in COVID-19 designated Routine Dialysis
hospital
ILI: Influenza Like Illness, NAT: Nucleic Acid Testing, HRCT: High Resolution Computerized Tomography, CBC: Complete Blood Count, CRP: C-Reactive protein
Figure 3. Management Protocol for Dialysis Patients Suspected to have COVID-19 Infection
6. Management of COVID-19 Patients with Liver Disease
6.1. Introduction
The incidence of elevated serum liver biochemistries in patients with COVID-19 (primarily
elevated AST and ALT, and slightly elevated bilirubin) ranges from 14% to 53%. Systemic
viral infections are often associated with transient elevations of transaminases which may
reflect general immune activation or inflammation caused by circulating cytokines without
compromising liver function, a phenomenon called “bystander hepatitis”. SARS-CoV-2 may
also directly infect Cells of biliary radicle as the receptor of the virus, angiotensin-
converting enzyme 2 (ACE2) , has been shown to be expressed on cholangiocytes which
may explain cases of viral shedding into the faeces.
The outcome of patients with liver injury is satisfactory, alterations of liver enzymes seem
usually transient and severe liver injury is rare. No death was documented to be directly
related to hepatic decompensation in patients without pre-existing liver disease so far.
Currently, there are limited data on the impact of pre-existing liver disease and the course of
SARS-CoV-2 infection. However, patients with advanced liver disease and recipients of
liver transplants represent vulnerable groups and are likely to be at an increased risk of
infection and/or a severe course of COVID-19.
6.2. General considerations
● It is important to stress that all general recommendations and guidelines with regards to
prevention, diagnosis and treatment of COVID-19 from local authorities must be
adhered to.
● The presence of abnormal liver biochemistries should not be a contraindication to using
investigational or off-label therapeutics for COVID-19.
● Regular monitoring of liver biochemistries should be performed in all COVID-19
patients.
● Acetaminophen at a daily dosage of ≤2 g/d is the preferred analgesic and anti-pyretic for
patients with known or suspected COVID-19.
● Serologic testing for hepatitis B and C and investigation of other causes of liver disease.
● Algorithm for managing COVID-19 patients with Liver Disease is presented in Figure 4.
51
6.3. Specific treatment considerations
● With regards to patients with chronic liver disease, possible adverse events have to be
kept in mind. This is particularly important with respect to drug-interactions in patients
with certain immunosuppressive therapies.
● In addition, patients with impaired liver function are at high risk of drug toxicities.
● The presence of abnormal liver biochemistries should not be a contraindication to using
investigational or off-label therapeutics for COVID-19.
Chloroquine/hydroxychloroquine
● Hydroxychloroquine therapy has not been associated with ALT abnormalities and
is an extremely rare cause of clinically apparent acute liver injury.
● Drug-interactions with immunosuppressive drugs: close monitoring of drug level
is required
Lopinavir/ritonavir
● The risk of lopinavir-associated hepatotoxicity in patients with very advanced liver
disease is low.
● Patients with decompensated cirrhosis should not be treated.
● Known and well-studied drug-interactions with immunosuppressive drugs.
Favipiravir
● Elevation of ALT and AST possible.
● No data in cirrhosis available.
Remdesivir
• No experience in liver cirrhosis but a nucleos(t)ide analogues(NUC) might be safer than
other drug classes based on experience with NUCs in chronic hepatitis B and C.
• Liver toxicity (elevated ALT) possible.
Tocilizumab
● ALT elevations are frequent but clinically apparent liver injury with jaundice seem to be
rare.
● Patients with decompensated cirrhosis should not be treated.
● Consider risk of HBV reactivation.
Convalescent plasma
● No experience in patients with chronic liver disease
52
Figure 4. Algorithm for Managing COVID-19 Patients with Liver Disease (EASL Guidelines)
53
7. Algorithm for Epistaxis in COVID-19 Positive Patients
PPE: full gear as the risk is doubled by aerosol and blood splash
Nasal pressure, 15 minutes

- Tranexamic acid
- Control of risk factors (blood pressure, aspirin, anticoagulants)
Bleeding continues: Bleeding cessation:

Silver nitrate cautery Topical Antibiotic
+/- alternative non-packing technique Follow up
Bleeding continues:
- Bilateral +/- posterior packs
- Significant medical co-morbidities
Bleeding continues:
Consider surgical intervention
• Full PPE
• Negative pressure theatre or
closed door theatre with
anteroom
• Closed suction
• Minimal technique
• Clipping rather cautery
54
8. Guideline Statements for Otologic Procedures in COVID-19
Positive Patients
Prof. Ahmed M. Mustafa; Head of Hearing & Speech Institute-ENT consultant
Prof. Ehab K. Sefein; Ass. consultant of ENT- Hearing & Speech Institute
Dr. Mohammad M. Gaballah; Fellow of ENT- Hearing & Speech Institute.
8.1. Mastoid Surgery

• The duration of the COVID-19 pandemic period is unclear but, assuming a 3-month
period before normal practice can resume, cholesteatoma surgery and cochlear
implantation, including in children, should not be regarded as urgent. Further guidance
will be offered in the event that ongoing precautions will be required beyond 3 months.
• Testing for COVID-19 is unlikely to be helpful as sensitivity of throat/nose swabs has
been reported to be as low as 32%. In addition, long turnaround times make testing
impractical. All patients should therefore be presumed to be positive.
• Significant aerosolisation of bone and other tissues occurs during mastoid drilling.
• Mastoid surgery should therefore be avoided unless there is a life-threatening urgency to
proceed.
• Urgent indications may include:
• Acute mastoiditis
• Otogenic intracranial sepsis
• Operable temporal bone malignancy.
• If mastoid drilling is unavoidable, drilling should be kept to a minimum and PPE
including FFP3 mask, close fitting eye protection (glasses are preferable to a visor),
water proof gown and gloves should be used as a minimum whilst not using the
microscope (subsequently referred to as full PPE).
• Use of the microscope may offer some degree of eye protection during drilling but
drilling should still be kept to a minimum. If possible, the surgeon should continue to
wear eye protection.
55
• Some clinicians may feel more comfortable using a hazmat suit with external
filtration if undertaking mastoid surgery, particularly if the patient is confirmed as
COVID-19 positive. The decision to use this level of protection lies with the clinician.
• A rigid otoscope with camera may be used instead of the microscope, accepting the
limitations of single-handed surgery if the PPE equipment makes use of the
microscope difficult.
• All unnecessary staff should leave theatre and those that remain should wear PPE as
above.
• For acute mastoiditis, curettage should be carried out rather than mastoid drilling, if
possible.
• If drilling is required, slowing drill speed, reducing irrigation volume and using
effective suction may reduce aerosolisation.
• Good hypotension will minimise bleeding and may also reduce aerosolisation.
• Surgery should be carried out by the most experienced otological surgeon available.
8.2. Other Otology Procedures

• Most otology procedures should be deferred until after the COVID-19 pandemic has
passed. Urgent cases (e.g. biopsy of suspected neoplasia) will need to be assessed on a
case-by-case basis.
• Full PPE as per mastoid surgery should be used.
• Additional guidance for microsuction. Significant aerosolisation of biological materials
may occur during microsuction, particularly with fenestrated suction.
• The risk of COVID-19 transmission with micro suction is; however, low, particularly
with wax clearance in the absence of inflammation. Nevertheless, full PPE as outlined
above is recommended.
• Unfenestrated suction probably reduces the risk of aerosolisation.
• Current opinion is that high dose steroid use to treat Meniere’s disease, Sudden
Sensorineural Hearing Loss (SSNHL) and idiopathic facial palsy (Bell’s palsy), whether
to manage Covid 19 infection or to treat an unrelated condition, may be associated with
a worse outcome.
56
• The systemic dose of steroid following intratympanic treatment is significantly lower
than that of oral treatment, and it is therefore likely that the impact on COVID-19
outcomes will be less. It is therefore preferable to use intra-tympanic steroid to treat
these conditions.
• If undertaking intra-tympanic treatments, it has been usual practice to ask the patient to
spit and not swallow for 20 minutes after the injection. This should be avoided during
the COVID-19 pandemic as spitting generates aerosol containing viruses.
• In idiopathic facial palsy, the use of oral steroids should be discussed with the patient.
Evidence from the Scottish Bell’s Palsy study suggests that the use of oral steroids
improves recovery from 85% to 96%
8.3. Necrotising Otitis Externa:

The fundamental management of necrotising otitis externa should not be affected by
COVID-19.
57
9. Guidelines for Tracheostomy on COVID19 Positive Patients
9.1. Logistics
58
9.2. Pre-operative
59
9.3. Procedure
60
9.4. Post-operative
61
10. Guidelines for Tonsillitis and Quinsy in COVID-19 Positive
Patients
Personal protection
• High flow O2
Equipment for all ENT Concerned about airway
examenations and AGPs: YES • Adrenaline
compromise or sepsis
• Surgical Gown nebulizer(1-5mg of
• Respirator (FPP3 1:1000)
or Equivelant) • Consider He liox
NO
• Eye protection • IV dexamethasone
• Gloves (with caution)
• Hat • IV Antibiotics
Treat with history alone when possible • Consider Resus
No
Resrve oral examination only to severe cases transfer
• Contact ENT
No History suspicious of Quinsy? &Anaesthsia
No
Refer to ENT
Can patient swallow medication? Avoid oral exam, consider:
Drainage
Betadine gargles
No
Initial treatment regime

IV Antibiotics
IV Dexamethasone (with caution)
IV fluids & analgesia
YES
CBC, liver functions, Kidney Functions, CRP, Glandular fever screen
Observe for 3-4 hours
yes
No
Can patient swallow?
Oral Antiiotics IV antibiotics
Oral Analgesia IV analgesia
Consider IV fluids
Short course of steroids (with caution) Quinsy not drained or case worsens?
PPI cover Surgery scheduled
Quinsy not drained or case worsens? with full PPE
precautions in
negative pressured
theatre and closed
suction, cold sugery ,
62 diathermy
avoid
11. Guidelines for STEMI
(1) Started within 30 minutes. Dose: I.V streptokinase 1.5 million units over 30-60 min. and preferably fibrin specific agent like
tPA or Tenecteplase
(2) Criteria for successful reperfusion: disappearance of chest pain within 90 minutes of starting SK infusion + resolution of ST-
segment elevation by > 50% after starting SK within 90 minutes ( in the lead with maximum elevation on baseline ECG)
(3) Plan for early discharge (2nd day) in patients with successful primary PCI + complete revascularization + no arrhythmias + no
CHF + age < 70 year + EF > 45%
(4) Discharge after 48 hours of successful fibrinolysis with arrangement of elective CA ± PCI may be considered as per policy of
each hospital and according to the availability of cath labs and staff. In those patients, intensification of DAPT (
Ticagrelor+Aspirin), subcutaneous enoxaparin or fondaparinaux, and follow-up telephone calls should be considered
63
12. Guidelines for NSTEMI
64
13. COVID-19 and Heart Failure
The corona virus disease-2019 (COVID-19) is an infectious disease caused by severe acute
respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular
care of patients. First, those with COVID-19 and preexisting cardiovascular disease (CVD)
have an increased risk of severe disease and death. Second, infection has been associated
with multiple direct and indirect cardiovascular complications including acute myocardial
injury, myocarditis, arrhythmias and venous thromboembolism. Third, therapies under
investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to
COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular
conditions.
Case fatality rates for comorbid patients are materially higher than the average population:
• Cancer: 5.6%
• Hypertension: 6.0%
• Chronic respiratory disease: 6.3%
• Diabetes: 7.3%
• Cardiovascular disease: 10.5%
Cardiomyopathy and heart failure. Zhou and colleagues reported that heart failure was
observed in 23.0% of patients with COVID-19 presentations. Notably, heart failure was
more commonly observed than acute kidney injury in this cohort and was more common in
patients who did not survive the hospitalization compared to those who did survive (51.9%
vs. 11.7%). Whether heart failure is most commonly due to exacerbation of pre-existing left
ventricular dysfunction versus new cardiomyopathy (either due to myocarditis or stress
cardiomyopathy) remains unclear.
Early reports indicate that there are two patterns of myocardial injury with COVID-19. The
rise in hs-cTnI tracks with other inflammatory biomarkers (D-dimer,ferritin, interleukin-6
(IL-6), lactate dehydrogenase), raising the possibility that this reflects cytokine storm or
secondary hemophagocytic lymphohistiocytosis more than isolated myocardial injury. In
contrast, reports of patients presenting with predominantly cardiac symptoms suggest a
different pattern, potentially viral myocarditis or stress cardiomyopathy.
65
COVID 19 on top of cardiomyopathy
Standard care with the following precautions
Diagnostic challenges
• Elevated cardiac markers especially troponin and NP should be assessed in the context of
clinical status and not interpreted as a sole marker of recent myocarditis
Deferring Non-Urgent CV Testing and Procedures During the COVID-19 Pandemic
● Cardiopulmonary exercise testing for functional assessment (outpatient and

inpatient)
● Right heart catheterization (outpatient)
● Surveillance right heart catheterization and cardiac biopsy post cardiac transplant
(outpatient)
● In-person cardiovascular implantable electronic device (CIED)

checks/interrogations (outpatient) and absent new cardiovascular symptoms
(inpatient)
● Cardioversions in stable, asymptomatic patients (outpatient and inpatient)
● Tilt table test (outpatient and inpatient)
● Implantable loop recorder (ILR) implant absent cryptogenic stroke (outpatient and
inpatient)
● Pacemaker implant for stable sinus node dysfunction or second-degree AV block
without syncope (outpatient and inpatient)
● ICD placement for primary prevention in stable, low-risk patients (outpatient)
● Upgrade to cardiac resynchronization therapy (CRT) in stable patients (outpatient
and inpatient)
● Atrial fibrillation ablation in stable patients (e.g., without refractory heart failure)
(outpatient and inpatient)
● Atrial flutter ablation in stable patients (e.g., without refractory heart failure)
(outpatient and inpatient)
66
Standard care with the following precautions as regards drug drug interactions
Antiviral treatment
Lopinavir/ritonavir may result in QT and PR interval prolongation, especially in patients
who have a baseline abnormality (long QT) or those who areat risk for conduction
abnormalities including those taking other QT prolonging drugs. Both ribavirin and
lopinavir/ritonavir have the potential to affect anticoagulant dosing: ribavirin has variable
effects on warfarin dosing (66) and lopinavir/ritonavir may require dose reductions or
avoidance of CYP3A mediated drugs such as rivaroxaban and apixaban.
Chloroquine and hydroxychloroquine
Both have effects of chloroquine on CYP2D6 inhibition, so beta-blockers metabolized via
CYP2D6 (such as metoprolol, carvedilol, propranolol, or labetalol) can have increased
concentration of drug requiring careful monitoring for heart rate and blood pressure shifts.
Also, both agents are associated with a conditional risk of torsade des pointes in patients
with electrolyte abnormalities or with concomitant use of QT prolonging agents
Methylprednisolone is another drug under investigation that is currently being used to treat
severe cases of COVID-19 that are complicated by ARDS (48). This steroid is known to
cause fluid retention, electrolyte derangement, and hypertension as direct CV effects, and
also may interact with warfarin via an undescribed mechanism.
RAAS-related treatments Be advised not to add or remove any RAAS-related treatments,
beyond actions based on standard clinical practice. Currently there are no experimental or
clinical data demonstrating beneficial or adverse outcomes with background use of ACE
inhibitors, ARBs or other RAAS antagonists in COVID-19 or among COVID-19 patients
with a history of cardiovascular disease treated with such agents. The HFSA, ACC, and
AHA recommend continuation of RAAS antagonists for those patients who are currently
prescribed such agents for indications for which these agents are known to be beneficial,
such as heart failure, hypertension, or ischemic heart disease
Arrhythmogenicity of Hydroxychloroquine and Azithromycin
The concerns regarding mortality risk, and the intensity of QT and arrhythmia monitoring
should be considered in the context of several important mitigating factors:
67
1. The duration of use for these medications for COVID-19 infection is short (5 to
10 days for acute illness).
2. While QT-prolonging medication use has been associated with increased risk of
death, the absolute magnitude is likely smaller than the potential benefit from
treatment of COVID-19 among specific subgroups with COVID-19 infection
(e.g., ICU-hospitalized patients and outpatients age >70).
3. There are large potential population-health benefits from hastening viral clearance
of COVID-19.
A risk score has been derived and validated by Tisdale et al., for prediction of drug-
associated QT prolongation among cardiac-care-unit-hospitalized patients .9 A Tisdale
score of ≤ 6 predicts low risk, 7-10 medium risk, and ≥ 11 high risk of drug-associated
QT prolongation, Table 5.
Table 5. Risk Score For Drug-Associated QTc Prolongation
Risk Factors Points
Age ≥68 y 1
Female sex 1
Loop diuretic 1
Serum K+ ≤3.5 mEq/L 2
Admission QTc ≥450 ms 2
Acute MI 2
≥2 QTc-prolonging drugs 3
Sepsis 3
Heart failure 3
One QTc-prolonging drug 3
Maximum Risk Score 21
K+ indicates potassium; and MI, myocardial infarction.
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Suggested Monitoring For Inpatient Clinical Use
Patients admitted with COVID-19 are likely to have longer baseline QTc and have higher
potential arrhythmic risks as a result of the metabolic and physiologic sequelae of their
illness, and a typically greater burden of comorbid disease. However, given the severity
of illness, hospitalized and critically ill patients may also derive the most benefit from
potentially effective therapies. The goal of QTc screening in this setting is not to identify
patients whom are not candidates for therapy, but to identify those who are at increased
risk for TdP so aggressive countermeasures may be implemented.
1. Baseline
a. Discontinue and avoid all other non-critical QT prolonging agents.
b. Assess a baseline ECG, renal function, hepatic function, serum potassium
and serum magnesium.
c. When possible, have an experienced cardiologist/electrophysiologist
measure QTc, and seek pharmacist input in the setting of acute renal or
hepatic failure.
2. Relative contraindications (subject to modification based on potential benefits of
therapy)
a. History of long QT syndrome, or
b. Baseline QTc >500 msec (or >530-550 msec in patients with QRS greater
than >120 msec)
3. Ongoing monitoring, dose adjustment and drug discontinuation
a. Place on telemetry prior to start of therapy.
b. Monitor and optimize serum potassium daily.
c. Acquire an ECG 2-3 hours after the second dose of hydroxychloroquine,
and daily thereafter.
d. If QTc increases by >60 msec or absolute QTc >500msec (or >530-550
msec if QRS >120 msec), discontinue azithromycin (if used) and/or
reduce dose of hydroxychloroquine and repeat ECG daily.
69
e. If QTc remains increased >60 msec and/or absolute QTc >500 msec (or
>530-550 msec if QRS >120 msec), reevaluate the risk/benefit of ongoing
therapy, consider consultation with an electrophysiologist, and consider
discontinuation of hydroxychloroquine.
Suggested Monitoring For Outpatient Clinical Use
Patients who are stable for outpatient therapy may be less at risk for complications, but
are unlikely to have access to close monitoring. As for inpatients, QTc screening should
be incorporated into an individualized risk-benefit consideration for treatment. Consider
the following, less intensive monitoring protocol:
1. Baseline
a. Discontinue and avoid all other non-critical QT prolonging agents.
b. Assess a baseline ECG, renal function, hepatic function, serum potassium
and serum magnesium.
c. When possible, have an experienced cardiologist/electrophysiologist
measure QTc.
d. Avoid outpatient initiation in the setting of acute renal or hepatic failure.
2. Relative contraindications (subject to modification based on potential benefits of
therapy)
a. History of long QT syndrome, or
b. Baseline QTc >480 msec (or >510-530 msec if QRS >120 msec), or
c. Tisdale risk score ≥11
3. Ongoing monitoring, dose adjustment and drug discontinuation
a. If quarantine or resource constraints are prohibitive, consider no further
ECG / telemetry assessment if Tisdale risk score ≤6. Also consider use of
alternative mechanisms of QT and arrhythmia assessment outlined below.
b. Otherwise, repeat ECG 2-3 hours after dosing on day 3 of therapy. If QTc
increases by >30-60 msec or absolute QTc >500msec (or >530-550 msec
if QRS >120 msec), consider discontinuing therapy.
70
Refer to QT Monitoring Protocol in Section 14.
Clinical Cardiovascular Concerns in COVID-19 Illness
Myocarditis and acute heart Failure in COVID 19
Early reports indicate that there are two patterns of myocardial injury with COVID-19.
The rise in hs-cTnI tracks with other inflammatory biomarkers (D-dimer,ferritin,
interleukin-6 (IL-6), lactate dehydrogenase), raising the possibility that this reflects
cytokine storm or secondary hemophagocytic lymphohistiocytosis more than isolated
71
myocardial injury. In contrast, reports of patients presenting with predominantly cardiac
symptoms suggest a different pattern, potentially viral myocarditis or stress
cardiomyopathy
Acute heart failure refers to rapid onset or worsening of symptoms and/or signs of HF. It
is a life-threatening medical condition requiring urgent evaluation and treatment,
typically leading to urgent hospital admission.
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73
Diagnostic issues
Chest X-ray can be a useful test for the diagnosis of AHF. Pulmonary venous congestion,
pleural effusion, interstitial or alveolar oedema and cardiomegaly are the most specific
findings for AHF, although in up to 20% of patients with AHF, chest X-ray is nearly
normal.519 Supine chest radiographs are of limited value in AHF. Chest X-ray is also
useful to identify alternative non-cardiac diseases that may cause or contribute to the
patient's symptoms (i.e. pneumonia, non-consolidative pulmonary infections).
ECG is rarely normal in AHF (high negative predictive value).520 It is also helpful in
identifying underlying cardiac disease and potential precipitants (rapid AF, acute myocardial
ischaemia). Immediate echocardiography is mandatory only in patients with haemodynamic
instability (particularly in cardiogenic shock) and in patients suspected of acute life-
threatening structural or functional cardiac abnormalities (mechanical complications, acute
valvular regurgitation, aortic dissection). Early echocardiography should be considered in all
patients with de novo AHF and in those with unknown cardiac function; however, the
optimal timing is unknown (preferably within 48 h from admission, if the expertise is
available). Pocket-size echocardiography may be used as an extension of the clinical
examination in the first instance where available. Repeated echocardiography is usually not
needed unless there is relevant deterioration in clinical status. Bedside thoracic ultrasound
74
for signs of interstitial oedema and pleural effusion may be useful in detecting AHF if the
expertise is available.
Laboratory tests:
• Natriuretic peptides.
• Upon presentation to the ED or CCU/ICU, a plasma NP level (BNP, NT-proBNP or MR-
proANP) should be measured in all patients with acute dyspnoea and suspected AHF to
help in the differentiation of AHF from non-cardiac causes of acute dyspnoea. NPs have
high sensitivity, and normal levels in patients with suspected AHF makes the diagnosis
unlikely (thresholds: BNP <100 pg/mL, NT-proBNP <300 pg/mL, MR-proANP <120
pg/mL).57–61,77,78,521 However, elevated levels of NPs do not automatically confirm
the diagnosis of AHF, as they may also be associated with a wide variety of cardiac and
non-cardiac causes . Unexpectedly low levels of NPs can be detected in some patients
with decompensated end-stage HF, flash pulmonary oedema or right sided AHF.
Management
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According to European Society of Intensive Care Medicine and the Society of Critical
Care Medicine 2020 Guidelines on the Management of Critically Ill Adults with
Coronavirus Disease 2019 (COVID-19)
Recommendation: 9. For the acute resuscitation of adults with COVID-19 and shock, we
suggest using a conservative over a liberal fluid strategy (weak recommendation, very low
quality evidence).
Recommendation: 10. For the acute resuscitation of adults with COVID-19 and shock, we
recommend using crystalloids over colloids (strong recommendation, moderate quality
evidence)
Recommendation: 16. For adults with COVID-19 and shock, we suggest using
norepinephrine as the first-line vasoactive agent, over other agents (weak recommendation,
low quality evidence).
Recommendation: 17. If norepinephrine is not available, we suggest using either vasopressin
or epinephrine as the first-line vasoactive agent, over other vasoactive agents, for adults with
COVID-19 and shock (weak recommendation, low quality evidence).
Recommendation: 18. For adults with COVID-19 and shock, we recommend against using
dopamine if norepinephrine is available (strong recommendation, high quality evidence).
Recommendation: 19. For adults with COVID-19 and shock, we suggest adding vasopressin
as a second-line agent, over titrating norepinephrine dose, if target mean arterial pressure
(MAP) cannot be achieved by norepinephrine alone (weak recommendation, moderate
quality evidence).
Recommendation: 20. For adults with COVID-19 and shock, we suggest titrating vasoactive
agents to target a MAP of 60-65 mmHg, rather than higher MAP targets (weak
recommendation, low quality evidence)
Recommendation: 21. For adults with COVID-19 and shock with evidence of cardiac
dysfunction and persistent hypoperfusion despite fluid resuscitation and norepinephrine, we
suggest adding dobutamine, over increasing norepinephrine dose (weak recommendation,
very low quality evidence).
Recommendation: 22. For adults with COVID-19 and refractory shock, we suggest using
low-dose corticosteroid therapy (“shock-reversal”), over no corticosteroid therapy (weak
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recommendation, low quality evidence). Remark: A typical corticosteroid regimen in septic
shock is intravenous hydrocortisone 200 mg per day administered either as an infusion or
intermittent doses
Recommendation: 40. In mechanically ventilated adults with COVID-19 and refractory
hypoxemia despite optimizing ventilation, use of rescue therapies, and proning, we suggest
using venovenous (VV) ECMO if available, or referring the patient to an ECMO center
(weak recommendation, low quality evidence).
Recommendations 41. In mechanically ventilated adults with COVID-19 and respiratory
failure (without ARDS), we suggest against the routine use of systemic corticosteroids
(weak recommendation, low quality evidence). 42. In mechanically ventilated adults with
COVID-19 and ARDS, we suggest using systemic corticosteroids, over not using
corticosteroids (weak recommendation, low quality evidence)
Recommendation: 45. In critically ill adults with COVID-19, we suggest against the routine
use of standard intravenous immunoglobulins (IVIG) (Weak recommendation, very low-
quality evidence).
Recommendation: 46. In critically ill adults with COVID-19, we suggest against the routine
use of convalescent plasma (Weak recommendation, very low quality evidence).
Recommendation 47. In critically ill adults with COVID-19:
47.1. we suggest against the routine use of lopinavir/ritonavir (weak recommendation, low
quality evidence).
47.2. There is insufficient evidence to issue a recommendation on the use of other antiviral
agents in critically ill adults with COVID-19.
Recommendation 48. There is insufficient evidence to issue a recommendation on the use of
recombinant rIFNs, alone or in combination with antivirals, in critically ill adults with
COVID-19.
chloroquine or hydroxychloroquine in critically ill adults with COVID-19.
tocilizumab in critically ill adults with COVID-19.
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14. Drug Related Factors to consider during Covid-19
14.1. Summary of Recommendations for Dosing and Monitoring of the

Selected COVID -19 Experimental Drugs
14.1.1 Introduction
A summary of dosing recommendations and monitoring of selected COVID-19
experimental therapies will be presented in this section. This evidence based part aims to
help practitioners better understand current approaches related to treatment and care of the
COVID-19. The authors have made reasonable efforts to ensure the accuracy and
appropriateness of the information presented. However, the information contained in this
evidence section is emerging and rapidly evolving because of ongoing research and is
subject to the professional judgment and interpretation of the practitioner based on the latest
evidence provided in COVID-19 management guide provided by the Egyptian Ministry of
Health and the needs of individual patients. Also the authors of this information are not
responsible for the continued currency of the information.
Treatment options suggested for COVID-19 disease are either virus-based therapies or host-
based therapies. Virus-based therapies include monoclonal antibodies and antiviral peptides
that target the viral spike glycoprotein, viral enzyme inhibitors, viral nucleic acid synthesis
inhibitors and inhibitors of other viral structural and accessory proteins. Host-based
therapies include agents that potentiate the interferon response or affect either host
signalling pathways involved in viral replication or host factors utilized by coronaviruses for
viral replication, Table 6.
14.1.2. Antimicrobials with potential activity against SARS-CoV-2:
• Antimalarials
A. Chloroquine
Rationale for Use Chloroquine has in vitro activity against SARS-CoV-2 and may have
immunomodulating properties.
Mechanism of Action
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Mechanisms may include inhibition of viral enzymes or processes such as viral DNA and
RNA polymerase, viral protein glycosylation, virus assembly, new virus particle
transport, and virus release. Other mechanisms may also involve ACE2 cellular receptor
inhibition, acidification at the surface of the cell membrane inhibiting fusion of the virus,
and immunomodulation of cytokine release.
Safety Concerns
o Risk of cardiac arrhythmias (e.g., QT prolongation)
o Risk of retinal damage, especially with long term use
o Caution in patients with G6PD deficiency
o Caution in diabetics
o Significant drug interactions (CYP2D6 and CYP3A4 substrate)
Contra-indications
●Known allergy to the drug
● Tisdale risk score ≥11
Precautions
QTc > 500 msec , hypokalemia, clinically significant drug-drug interactions, G6PD
deficiency, Myasthenia gravis , Porphyria , Retinal pathology , Epilepsy , Uncontrolled
diabetes, use with caution if renal impairment, taking
Dosing Adult/Treatment Duration
≥50 kg: Oral: 1 g (600 mg base) once on day 1 followed by 500 mg (300 mg base) once
daily (FDA 2020). Duration: 4-7 days
Monitoring
Monitor QT-prolonging effects during therapy in at-risk patients or if used in
combination with other medications that prolong the QT interval
Monitor glucose level in diabetic patients
Dosing: Renal Impairment: Adult
There are no dosage adjustments provided in the manufacturer’s labeling; the following
guidelines have been used by some clinicians (Aronoff 2007):
GFR ≥10 mL/minute: No dosage adjustment necessary.
GFR <10 mL/minute: Administer 50% of dose.
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Hemodialysis, peritoneal dialysis: Administer 50% of dose.
Continuous renal replacement therapy (CRRT): No dosage adjustment necessary.
Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling; use with
caution.
Dosing in Infants, Children, and Adolescents weighing less than 50 kg Efficacy and
optimal dosing not established; however, based on extrapolation from pediatric dosing for
other indications and comparative doses to the adult dosing regimen suggested for
COVID-19, 8.3 mg (5 mg base)/kg/dose PO twice daily [Max: 500 mg/dose (300 mg
base/dose)] is being used in limited pediatric dosing protocols; a 10-day course is being
used in adult patients.
Dosing in Adolescents weighing 50 kg or more Data are limited; efficacy has not been
established. 1000 mg PO on day 1 then 500 mg PO daily for 4 to 7 days suggested by
FDA EUA statement. Based on extrapolation from pediatric dosing for other indications
and comparative doses to the adult dosing regimen suggested for COVID-19, 8.3 mg (5
mg base)/kg/dose PO twice daily [Max: 500 mg/dose (300 mg base/dose)] is being used
in limited pediatric dosing protocols; a 10-day course is being used in adult patients.
Dosing: Renal Impairment: Pediatric
There are no dosage adjustments provided in the manufacturer’s labeling; in adult
patients, dosage adjustment suggested.
Dosing: Hepatic Impairment: Pediatric

caution.
B. Hydroxychloroquine
Rationale for Use Hydroxychloroquine has in vitro activity against SARS-CoV-2 and
may have immunomodulating properties.
Mechanism of Action Mechanisms may include inhibition of viral enzymes or processes
such as viral DNA and RNA polymerase, viral protein glycosylation, virus assembly,
new virus particle transport, and virus release. Other mechanisms may also involve ACE2
80
cellular receptor inhibition, acidification at the surface of the cell membrane inhibiting
fusion of the virus, and immunomodulation of cytokine release.
Safety Concerns: less common than chloroquine
o Risk of retinal damage, especially with long term use
o Caution in patients with G6PD deficiency
o Caution in diabetics
o Significant drug interactions (CYP2D6, CYP3A4, CYP3A5, and CYP2C8
substrate)
Contra-indications
●Known allergy to the drug
● Tisdale risk score ≥11
Precautions
QTc > 500 msec , hypokalemia, clinically significant drug-drug interactions, G6PD
deficiency, Myasthenia gravis , Porphyria , Retinal pathology , Epilepsy , Uncontrolled
diabetes, use with caution if renal impairment, taking
Dosing Adult/Treatment Duration
Regimen1: Oral 400 mg twice daily on day 1, followed by 400 mg/day as a single dose or
in 2 divided doses, for a total treatment duration of 5 days (Kim 2020; Yao 2020) or (5
days)
Regimen 2: 800 mg once on day 1, followed by 400 mg/day as a single dose or in 2
divided doses, for a total treatment duration of 4 to 7 days (FDA 2020; Perinel 2020). (4-
7 days)
Monitoring
Monitor QT-prolonging effects during therapy in at-risk patients or if used in
combination with other medications that prolong the QT interval
Monitor glucose level in diabetic patients
There are no dosage adjustments provided in the manufacturer’s labeling; renal clearance
accounts for 15 to 25% of total clearance (Tett 1993); not dialyzable (Jallouli 2015).
Dosage reduction may be needed with chronic use (Tett 1993); use with caution.
81
caution.
Dosing in Pediatric Patients: Some experts have recommended interim pediatric
dosing as follows:
Children and Adolescents Oral: 6.5 mg/kg/dose hydroxychloroquine sulfate twice daily
on day 1; maximum day 1 dose: 400 mg/dose; followed by 3.25 mg/kg/dose
hydroxychloroquine sulfate twice daily on days 2 through 5; maximum dose: 200
mg/dose (ASTCT 2020). Note: These dosing recommendations are specifically for
patients who have undergone hematopoietic cell transplant (HCT) or other cellular
therapy. However, some centers are reporting internal protocols/plans to use this dose in
hospitalized pediatric patients who are not HCT patients.

There are no dosage adjustments provided in the manufacturer's labeling; renal clearance
accounts for 15% to 25% of total clearance (Tett 1993); not dialyzable (Jallouli 2015).
Dosage reduction may be necessary with chronic use (Tett 1993); use with caution.

caution.
II- Antivirals
A. Lopinavir and Ritonavir
Classification HIV Protease Inhibitor
Rationale for Use In vitro and animal model studies show potential activity for other
coronaviruses (SARS-CoV and MERS-CoV). Lopinavir and ritonavir may bind to Mpro,
a key enzyme for coronavirus replication. This may suppress coronavirus activity.
Safety Concerns:
o Caution in patients with hepatic disease or hepatitis
o Significant drug interactions
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o Gastrointestinal intolerance, nausea, vomiting, diarrhea.
o Pancreatitis
o Drug-drug interactions: CYP3A4 inhibitor and substrate; CYP2D6 substrate;
CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 inducer. P-gp substrate;
UGT1A1 inducer
Contraindications
Hypersensitivity, coadministration with drugs that are highly dependent on CYP3A for
clearance and for which elevated plasma concentrations are associated with serious
and/or life-threatening reactions or with potent CYP3A inducers where significantly
decreased lopinavir levels may be associated with a potential for loss of virologic
response and resistance and cross-resistance to develop (eg, alfuzosin, apalutamide,
dronedarone, colchicine [patients with renal and/or hepatic impairment],
elbasvir/grazoprevir, ergot derivatives [eg, dihydroergotamine, ergotamine,
methylergonovine], lomitapide, lovastatin, lurasidone, oral midazolam, pimozide,
ranolazine, rifampin, sildenafil [when used to treat pulmonary arterial hypertension],
simvastatin, St John's wort, triazolam).
Dosing in Adults/Treatment Duration
200mg / 50mg tablet), two tablets each time, twice daily (No more than 14 days)
There are no dosage adjustments provided in the manufacturer's labeling (has not
been studied); however, a decrease in clearance is not expected.
Hemodialysis: Avoid once-daily dosing in hemodialysis patients (HHS [adult]

2019).

Mild to moderate impairment: There are no dosage adjustments provided in the
manufacturer's labeling; however, lopinavir is primarily metabolized by the liver and
its AUC may be increased ~30%; use with caution.
Severe impairment: There are no dosage adjustments provided in the manufacturer's

labeling (has not been studied); use with caution.
83
Dosing: Pediatric
Coronavirus disease 2019 (COVID-19): Lopinavir/ritonavir is currently under
investigation for use in the treatment of COVID-19 (See ClinicalTrials.gov). Whenever
possible, treatment should be given as part of a clinical trial. At this time, safety and
efficacy have not been established in adult or pediatric patients. Surviving Sepsis
Campaign guidelines suggest against the routine use of lopinavir/ritonavir in critically ill
adults with COVID-19 at this time; pediatric patients are not addressed (Alhazzani
2020). If evidence to support safety and efficacy becomes available, dosing
recommendations may be provided.
Gene mutation and antiretroviral (ARV) resistance patterns should be evaluated (refer
to https://www.iasusa.org/ for more information) when necessary. Health care providers
are reminded that lopinavir/ritonavir oral solution is highly concentrated. Dosage is based
on patient body weight (mg/kg) or body surface area (mg/m2); use precaution during dose
calculation; dosing is presented based on lopinavir component. To minimize the risk for
medication errors, health care providers should pay special attention to accurate
calculation of the dose, transcription of the medication order, dispensing information,
dosing instructions, and proper measurement of the dose. Unlike adults, once daily
dosing is subtherapeutic and not recommended for use in pediatric patients (HHS
[pediatric] 2019).
B. Remdesivir (GS-5734)
Classification Investigational Nucleoside Analogue
Rationale for Use Remdesivir is a broad-spectrum antiviral with in vitro activity against
coronaviruses.
Mechanism of Action Remdesivir is a monophosphoramidate prodrug of remdesivir-
triphosphate (RDV-TP), an adenosine analog that acts as an inhibitor of RNA-dependent
RNA polymerases (RdRps). Remdesivir-TP competes with adenosine-triphosphate for
incorporation into nascent viral RNA chains. Once incorporated into the viral RNA at
position i, RDV-TP terminates RNA synthesis at position i+3. Because RDV-TP does not
84
cause immediate chain termination (i.e., 3 additional nucleotides are incorporated after
RDV-TP), the drug appears to evade proofreading by viral exoribonuclease (an enzyme
thought to excise nucleotide analog inhibitors). Coronavirus disease 2019 (COVID-19),
treatment: No data available; trials ongoing:
Dosing adults/Treatment Duration
IV 200 mg as a single dose on day 1, followed by 100 mg once daily (5-10 days)
Safety Concerns
Not commercially available; most promising antiviral currently being investigated for
COVID-19 Safety and efficacy not established; additional data needed
Dosing: Pediatric
Remdesivir is currently under investigation for use in the treatment of COVID-19
(see ClinicalTrials.gov). Pediatric patients with severe disease are being considered for
compassionate use access. At this time, safety and efficacy have not been established in
adult or pediatric patients; as data and experience in pediatric patients continue to evolve,
dosing will be updated as appropriate. Whenever possible, treatment should be given as
part of a clinical trial. No specific drug-drug interaction data are available. Minimize any
unnecessary comedication whenever possible given lack of information about interaction
risk.
Children and Adolescents ≤17 years: Dosing based on clinical experience and trials in
pediatric patients treated for Ebola virus disease (WHO 2018); optimal dose has not been
established for COVID-19. Optimal duration for treatment of COVID-19 not established;
total duration of 5 to 10 days is being evaluated in clinical trials in adults with COVID-19
(NIH 2020a; NIH 2020b; NIH 2020c). In pediatric Ebola virus experience, doses were
infused over 30 minutes (WHO 2018).
• <40 kg: IV: 5 mg/kg/dose as a single dose on day 1, followed by 2.5 mg/kg/dose
once daily.
• ≥40 kg: IV: 200 mg as a single dose on day 1, followed by 100 mg once daily.
• Adolescents ≥18 years: IV: 200 mg as a single dose on day 1, followed by 100
mg once daily for a total duration of 5 to 10 days; dosing based on ongoing
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clinical trials for COVID-19 in adults (Gilead 2020; NIH 2020a; NIH 2020b; NIH
2020c).
C. Favipiravir
Mechanism of Action The mechanism of action of favipiravir is novel compared to

existing influenza antivirals that primarily prevent entry and exit of the virus from cells.
The active favipiravir-RTP selectively inhibits RNA polymerase and prevents
replication of the viral genome
Dosing Adults/Treatment Duration
1,600 mg twice daily on day 1, followed by 600 mg twice daily for a total duration of 7 to
14 days (Cai 2020; NIH 2020a). OR 7 to 14 days (Cai 2020; NIH 2020a). Optimal dose
and duration unknown limited data available
Dose of 2.4 g every 8 hours for 2 doses, followed by a dose of 1.2 g 8 hours later on day
1, followed by 1.2 g twice daily. 7 to 10 days (NIH 2020b).
Safety Concerns
It causes Hyperuricemia, diarrhea, elevated transaminases, reduction in neutrophil count
Metabolism/Transport Effects
Inhibits CYP2C8 (weak) and aldehyde oxidase inhibitor, metabolized by aldehyde
oxidase and xanthine oxidase
Interactions
A. Influenza Virus Vaccine (Live/Attenuated): Antiviral Agents (Influenza A and B)
may diminish the therapeutic effect of Influenza Virus Vaccine (Live/Attenuated).
Management: Avoid anti-influenza antivirals during the period beginning 48 hours
prior to and ending 2 weeks after live influenza virus vaccine administration. Risk D:
Consider therapy modification
B. Pyrazinamide: Favipiravir may enhance the adverse/toxic effect of Pyrazinamide.
Specifically, the risk for increased uric acid concentrations may be increased. Risk C:
Monitor therapy
C. Repaglinide: CYP2C8 Inhibitors (Weak) may increase the serum concentration of
Repaglinide. Risk C: Monitor therapy
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III- Adjunctive/Supportive therapy:
A. Azithromycin
Classification Macrolide Antibacterial
Rationale for Use Azithromycin may prevent bacterial superinfection, and macrolides
may have immunomodulatory properties to work as adjunct therapy.
Mechanism of Action: Macrolides may have immunomodulatory properties in
pulmonary inflammatory disorders. They may downregulate inflammatory responses and
reduce the excessive cytokine production associated with respiratory viral infections;
however, their direct effects on viral clearance are uncertain. Immunomodulatory
mechanisms may include reducing chemotaxis of neutrophils (PMNs) to the lungs by
inhibiting cytokines (i.e., IL-8), inhibition of mucus hypersecretion, decreased production
of reactive oxygen species, accelerating neutrophil apoptosis, and blocking the activation
of nuclear transcription factors.
Safety Concerns
Risk of cardiac arrhythmias (e.g., QT prolongation)
Significant drug interactions
Altered cardiac conduction
Hepatic impairment: Use with caution in patients with preexisting liver disease
Use with caution in patients with myasthenia gravis
Use with caution in patients with severe renal impairment (GFR <10 mL/minute);
increased gastrointestinal adverse effects may occur
Dosing Adults
Azithromycin 500 mg PO on day 1 then 250 mg PO once daily for 5-10 days with
hydroxychloroquine has been used. ( 5 days)
Monitoring parameters
Liver function tests, CBC with differential.
Discontinue immediately if symptoms of hepatitis occur (malaise, nausea, vomiting,
Use with caution in patients with GFR <10 mL/minute (AUC increased by 35%
compared to patients with normal renal function); however, no dosage adjustment is
87
provided in the manufacturer's labeling.
No supplemental dose or dosage adjustment necessary, including patients on intermittent
hemodialysis, peritoneal dialysis, or continuous renal replacement therapy (eg, CVVHD)
(Aronoff 2007; Heintz 2009).

Azithromycin is predominantly hepatically eliminated; however, there is no dosage
adjustment provided in the manufacturer's labeling. Use with caution due to potential for
hepatotoxicity (rare); discontinue immediately for signs or symptoms of hepatitis.
Dosing: Pediatric
Coronavirus disease 2019 (COVID-19): Azithromycin, in combination with
hydroxychloroquine, was described in 1 small, open-label, nonrandomized study in

hospitalized adult patients (mean age of treated patients: 51.2 ± 18.7 years) with COVID-
19 and appeared to have additive benefit in reducing viral carriage (Gautret 2020). Due to
the limitations of this trial and the small number of patients who received azithromycin
(n=6) the role of azithromycin in the management of COVID-19 has not been established.
Azithromycin continues to be under investigation for use in the treatment of COVID-19
(See ClinicalTrials.gov). Whenever possible, treatment should be given as part of a
clinical trial. No studies in pediatric patients have been reported. If evidence
demonstrating safety and efficacy becomes available, dosing recommendations may be
provided.
B. Tocilizumab
Classification Interleukin-6 (IL-6) Receptor-Inhibiting Monoclonal Antibody
Rationale for Use Cytokine release syndrome may be a component of severe disease in
COVID-19 patients.
Mechanism of Action: Tocilizumab inhibits IL-6-mediated signaling by competitively
binding to both soluble and membrane-bound IL-6 receptors. IL-6 is a proinflammatory
cytokine that is involved in diverse physiological processes such as T-cell activation,
immunoglobulin secretion induction, hepatic acute-phase protein synthesis initiation, and
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hematopoietic precursor cell proliferation and differentiation stimulation. IL-6 is
produced by various cell types, including T- and B-cells, lymphocytes, monocytes, and
fibroblasts.
Safety Concerns
o Risk of GI perforation
o Risk of hepatotoxicity
o Caution in patients with thrombocytopenia and neutropenia
o Infusion-related reactions
o Drug-drug interactions: In vitro data suggested that IL-6 reduces mRNA expression for
several
CYP450 isoenzymes, including CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, and
CYP3A4. May decrease levels of substrates
Dosing Adults/Treatment Duration
Tocilizumab Solution for injection; Adults: Available data are limited, and efficacy has
not been established.
IV: Limited data available; dosing used in clinical trials includes the following:
8 mg/kg (maximum: 800 mg/dose) as a single dose; may repeat dose in 8 to 12 hours if
signs/symptoms worsen or do not improve
8 mg/kg (maximum: 800 mg/dose) every 12 hours for 2 doses
8 mg/kg as a single dose
4 to 8 mg/kg (usual dose: 400 mg/dose; maximum: 800 mg/dose) as a single dose; may
repeat dose in ≥12 hours in patients who remain febrile within 24 hours of initial dose
Monitoring Parameters
Latent TB screening prior to therapy initiation (all patients); neutrophils, platelets (prior
to therapy, 4 to 8 weeks after start of therapy, and every 3 months thereafter [rheumatoid
arthritis {RA}, giant cell arteritis {GCA}]); ALT/AST, alkaline phosphatase, and total
bilirubin (prior to therapy, every 4 to 8 weeks after start of therapy for the first 6 months,
and every 3 months thereafter [RA, GCA]); neutrophils, platelets, ALT/AST (prior to
therapy, at second administration, and every 2 to 4 weeks [systemic juvenile idiopathic
89
arthritis] or 4 to 8 weeks [polyarticular juvenile idiopathic arthritis] thereafter); additional
liver function tests (eg, bilirubin) as clinically indicated; lipid panel (prior to and 4 to 8
weeks following initiation of therapy, then subsequently according to current guidelines);
monitor all patients for signs and symptoms of infection (prior to, during, and after
therapy); signs and symptoms of CNS demyelinating disorders

CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the manufacturer's
labeling (has not been studied).

Hepatic impairment prior to treatment initiation: There are no dosage adjustments
provided in the manufacturer's labeling (has not been studied). Initiation of therapy in
patients with active hepatic disease or hepatic impairment or in rheumatoid arthritis (RA)
and giant cell arteritis (GCA) patients with baseline ALT or AST >1.5 × ULN is not
recommended.
Dosing: Pediatric
Cytokine release syndrome (CRS) due to coronavirus disease 2019 (COVID-19): No
data available
Tocilizumab is currently under investigation for use in the treatment of COVID-19
associated
pulmonary complications with elevated IL-6 levels (see ClinicalTrials.gov). At this time,
safety and efficacy have not yet been established in adult or pediatric patients. As data
and experience in pediatric patients continue to rapidly evolve, dosing will be updated as
appropriate. Institutional protocols may vary; if available, institution-specific dosing
recommendations should be followed. Whenever possible, treatment should be given as
part of a clinical trial. Preliminary dosing information provided here is based on clinical
trials in process.
90
Infants, Children, and Adolescents IV: 8 mg/kg/dose once; an additional dose may be
given 12 hours after the first if clinical symptoms worsen or show no improvement;
maximum dose: 800 mg/dose (NIH 2020b; NIH 2020d). Note: Higher doses have been
used in patients <30 kg in other indications.
C. Ostelamivir
Classification: Antiviral Agent; Neuraminidase Inhibitor
Safety Concerns:
Anaphylaxis/hypersensitivity: Rare but severe hypersensitivity reactions
Neuropsychiatric events: Rare occurrences of neuropsychiatric events (including
confusion, delirium, hallucinations, and/or self-injury)
Cardiovascular disease: Use with caution in patients with chronic cardiac disease.
Hepatic impairment: Use with caution in patients with severe hepatic impairment; safety
and efficacy have not been established.
Renal impairment: Use with caution; dosage adjustment is required for patients with renal
impairment. Not recommended for patients with end stage renal disease (ESRD) not
undergoing dialysis.
Respiratory disease: Use with caution in patients with respiratory disease.
Dosing Adult
Oseltamivir is currently under investigation for use in the treatment of COVID-19

(see ClinicalTrials.gov). Whenever possible, treatment should be given as part of a
clinical trial. At this time, safety and efficacy have not been established.
Influenza, seasonal, treatment: Oral: 75 mg twice daily (CDC 2018a). Note: Higher
doses (150 mg twice daily) are not currently recommended even in severely ill or
immunocompromised patients (Ariano 2010; CDC 2018a; Lee 2013; SEAICRN 2013).
Five days (a longer duration can be considered in severely ill or immunocompromised
patients (CDC 2018a).
91
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium
benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl
alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated
with a potentially fatal toxicity (“gasping syndrome”) in neonates.
• Sorbitol: Oral suspension contains sorbitol (delivers ~2 g sorbitol per 75 mg dose)

which is greater than the maximum daily limit for patients with hereditary
fructose intolerance; may cause diarrhea and dyspepsia; use with caution.

Influenza, seasonal, treatment:
CrCl >60 mL/minute: No dosage adjustment necessary
CrCl >30 to 60 mL/minute: 30 mg twice daily
CrCl >10 to 30 mL/minute: 30 mg once daily
ESRD not undergoing dialysis: Use is not recommended (has not been studied)
Intermittent hemodialysis (IHD) (CrCl ≤10 mL/minute):
Treatment: 30 mg immediately and then 30 mg after every hemodialysis session for 5

days. Note: Assumes three hemodialysis sessions in the 5-day period.
Alternative recommendations: Treatment (AMMI Canada [Aoki 2012]):
Low-flux hemodialysis: 30 mg after each dialysis session for 5 days
High-flux hemodialysis: 75 mg after each dialysis session for 5 days
Continuous ambulatory peritoneal dialysis (CAPD):
Treatment: 30 mg immediately as a single dose (single dose provides a 5-day duration)
Note: For patients receiving aggressive automated peritoneal dialysis (APD) with
negligible or low residual renal function, a small pharmacokinetic study suggests that 75
mg as a single dose for treatment would produce drug exposure at the upper limit of the
safety margin (Patel 2015).
92
Continuous renal replacement therapy (CRRT) (high-flux):
Treatment (off-label dose; limited data): 30 mg once daily for 5 days or 75 mg every 48
hours to provide a 5-day duration (AMMI Canada [Aoki 2012]; Ariano 2010)
Continuous veno-venous hemodialysis (CVVHD): Note: Limited information

available; optimal dosing has not been established: 150 mg twice daily administered via
nasogastric or postpyloric feeding tube for suspected or confirmed H1N1 influenza
demonstrated supratherapeutic oseltamivir carboxylate concentrations at effluent rates of
3,300 ± 919 mL/hour; the authors determined that the manufacturer recommended dosage
of 75 mg once daily for patients with CrCl 10 to 30 mL/minute will likely achieve
concentrations necessary to inhibit viral neuraminidase activity at these effluent rates;
however, doses >75 mg once daily may be required when using higher effluent rates
(Eyler 2012).
CVVHD and concurrent use of ECMO: Lower oseltamivir carboxylate concentrations

(~981 ng/mL) were observed as compared to those with the use of CVVHD alone
(~2,760 ng/mL) when patients were administered 150 mg twice daily for suspected or
confirmed H1N1 influenza (n=4; Eyler 2012).

Mild-to-moderate impairment: No dosage adjustment necessary.
Severe impairment: No dosage adjustment provided in manufacturer’s labeling
(has not been studied).
Dosing: Obesity: Adult

In adult morbidly obese patients (BMI >40 kg/m2), systemic exposure of oseltamivir
carboxylate was not reduced; therefore, no dosage adjustment is necessary (Thorne-
Humphrey 2011).
Dosing: Pediatric
Coronavirus disease 2019 (COVID-19): Oseltamivir is currently under investigation for
use in the treatment of COVID-19 (See ClinicalTrials.gov). Whenever possible, treatment
should be given as part of a clinical trial. At this time, safety and efficacy have not been
93
established. If evidence demonstrating safety and efficacy becomes available, dosing
recommendations may be provided.
Influenza, treatment: Note: Treatment should ideally begin within 48 hours of illness
onset; however, initiation after 48 hours is recommended for patients with severe,
complicated, or progressive illness; hospitalized patients; or those at increased risk for
complications (see Use for additional information). Initiate as early as possible in any
hospitalized patient with suspected/confirmed influenza (CDC 2019).
The usual duration of therapy is 5 days; a longer duration may be necessary in severely ill
or immunocompromised patients (CDC 2019).
Infants ≤8 months: Oral: 3 mg/kg/dose twice daily (AAP 2019; CDC 2019; IDSA
[Uyeki 2019]; IDSA/PIDS [Bradley 2011]).
Infants ≥9 months: Oral: 3.5 mg/kg/dose twice daily (AAP 2019; IDSA [Uyeki 2019]);
some experts still recommend 3 mg/kg/dose twice daily (CDC 2019; IDSA [Uyeki
2019]).
Children and Adolescents:
≤15 kg: Oral: 30 mg twice daily.
>40 kg: Oral: 75 mg twice daily.

Children and Adolescents: Treatment: Limited data available (Schreuder 2010):
Intermittent hemodialysis (IHD) (CrCl ≤10 mL/minute): Fixed dosing:
≤15 kg: 7.5 mg after each hemodialysis session
>15 kg to ≤23 kg: 10 mg after each hemodialysis session
>23 kg to ≤40 kg: 15 mg after each hemodialysis session
>40 kg: 30 mg after each hemodialysis session
94
Mild to moderate impairment: No dosage adjustment necessary.
Severe impairment: There are no dosage adjustments provided in manufacturer's labeling
(has not been studied).
D. Corticosteroids
• Corticosteroid therapy is not recommended for viral pneumonia; however, use may be
considered for patients with refractory shock or acute respiratory distress syndrome.
E. NSAIDs
• The FDA continues to investigate the use of NSAIDs in patients with COVID-19
symptoms.
• Concern for potential worsening of COVID-19 symptoms has been suggested, but
confirmatory clinical data is lacking at this time.There is an anecdotal published letter
that suggests a link between ibuprofen and increased ACE2 expression that may lead to
worse outcomes in COVID-19 patients.
• Acetaminophen may be considered for temperature control.
• ESICM and SCCM Surviving Sepsis Campaign recommendations suggest
acetaminophen for temperature control in critically ill adults with COVID-19 who
develop fever.
IV- Other treatments being evaluated include
Other immunomodulating agents (e.g., alfa-interferon, sarilumab) are being evaluated as
adjunctive therapy and COVID-19 Convalescent Plasma
95
V- Selected Drugs in Pregnancy
Chloroquine phosphate May be used in pregnancy if benefit
outweighs risks
Hydroxychloroquine sulfate May be used in pregnancy if benefit
outweighs risks
Lopinavir/ritonavir May be used in pregnancy; avoid oral
solution if possible due to ethanol content
Remdesivir Safety in pregnancy unknown, currently
recommended to avoid
Favipiravir Favipiravir is contraindicated in women
with known or suspected pregnancy and
precautions should be taken to avoid
pregnancy during treatment with the drug,
metabolite found in breast milk. Early
embryonic deaths and teratogenicity
observed in animal studies.
Tocilizumab Safety in pregnancy unknown; may cause
harm to the fetus
Ostelamivir May be used in pregnancy
96
97
98
99
100
101
14.2. Important Drug-drug Interactions with Covid-19 Therapies
LPV/r RDV FAVI CLQ HCLQ RBV TCZ INFN-ᵝ

Antivirals-Covid
Lopinavir/ritonavir*
Remdesevir
Favipiravir
Chloroquine*
Hydroxychloroquine*
Ribavirin
Tocilizumab
Interferon beta
Antifungals
Fluconazole*
Itraconazole
Ketoconazole
Voriconazole
Antibacterials
Azithromycin*
Ciprofloxacin*
Moxifloxacin*
Clarithromycin*
Clindamycin
Erythromycin*
Isoniazid
Levofloxacin*
Linezolid
Metronidazole
Pyrazinamide
Rifampicin
75%
LPV/r: Lopinavir/ritonavir, RDV: Remdesevir, FAVI: Favipiravir, CLQ: Chloroquine, RBV: Ribavirin, HCLQ:
Hydroxychloroquine, TCZ: Tocilizumab, INFN-ᵝ= Interferon beta. * = Identified by www.crediblemeds.org as
having a known or possible QTor TdP risk
Key to Symbols
Should not be co-administered
Potential interaction – may require close monitoring, alteration of drug dosage or timing of administration
Potential interaction likely to be of weak intensity. Additional action/monitoring or dosage adjustment is
unlikely to be required
No clinically significant interaction expected
= Potential increased exposure of the comedication, = Potential decreased exposure
of the comedication, = Potential increased exposure of covid drug, = Potential
decreased exposure of covid drug
102

Anaesthetics, muscle relaxants
Propofol*
Dexmedetomidine*
Atracurium
Ketamine
Analgesics
Fentanyl
Morphine
Pethidine
Tramadol*
Anxiolytics/sedatives
Alprazolam
Bromazepam
Diazepam
Midazolam (Parenteral)
Midazolam (oral)
Antipsychotics/Neuroleptics
Clozapine*
Haloperidol*
Quetiapine
Olanzapine
Resperidone
Anticonvulsants
Carbamazepine
Phenytoin
Valproate
3
38%
8
% INFN-ᵝ= Interferon beta. * = Identified by www.crediblemeds.org as
Hydroxychloroquine, TCZ: Tocilizumab,
having a known or possible QTor TdP risk.
Key to Symbols
103
LPV/r* RDV FAVI CLQ* HCLQ* RBV TCZ INFN-ᵝ
Antidepressants
Amitriptyline
Citalopram*
Escitalopram*
Fluoxetine
Lithium*
Paroxetine
Sertraline
St John’s wort
Immunosuppressants
Adalimumab
Azathioprine
Basiliximab
Ciclosporin
Mycophenolate
Pirfenidone
Sirolimus
Tacrolimus*
Bronchodilators
Aminophylline/Theophylline
Montelukast
Anti-diabetics
Canagliflozin
Glibenclamide/ Glyburide
Gliclazide/Glimepride/Glipizide
Pioglitazone
Repaglinide
52%
Rosiglitazone
Saxagliptin
Key to Symbols
Potential interaction likely to be of weak intensity. Additional action/monitoring or dosage adjustment is unlikely to be
required
= Potential increased exposure of the comedication, = Potential decreased exposure of the
comedication, = Potential increased exposure of covid drug, = Potential decreased exposure of
covid drug
104

Antithrombotics
Apixaban
Clopidogrel
Dabigatran
Dipyridamole
Rivaroxaban
Ticagrelor
Warfarin
Steroids
Budesonide
Dexamethasone
Hydrocortisone (oral)
Methylprednisolone
Prednisolone
Prednisone
Gastrointestinal agents
Antacids
Bisacodyl/Senna
Omeprazole/Pantoprazole
Ranitidine/Famotidine
Aprepitant
Domperidone*
Metoclopramide
Ondansetron*
Prochlorperazine
Key to Symbols
105
Lipid lowering agents
Atorvastatin
Gemfibrozil
Lovastatin
Rosuvastatin
Simvastatin
Antiarrhythmics
Amiodarone*
Lidocaine
Propafenone
Mexiletine
Hypertension/Heart Failure/Pulmonary hypertension
Aliskiren
Bosentan
Digoxin
Doxazosin
Eplerenone
Indapamide
Isosorbide dinitrate
Irbesartan
Ivabradine
Labetalol
Losartan
Prazosin
Ranolazine
Sacubitril
Sildenafil
Torasemide
Valsartan
Key to Symbols
106
LPV/r RDV FAVI CLQ HCLQ RBV TCZ INFN-

ᵝ
Beta Blockers
Atenolol
Bisoprolol
Carvedilol
Metoprolol
Nebivolol
Propranolol
Calcium Channel Blockers
Amlodipine
Diltiazem
Felodipine
Nicardipine*
Nifedipine
Verapamil
Key to Symbols
Notes
• Please check http://www.covid19druginteractions.org, http://www.hiv-
druginteractions.org, http://www.hep-druginteractions.org, http://www.cancer-
druginteractions.org for updates or any suspected drug-drug interactions not in the
above list
• Ostelamivir increase concentration of Favipiravir by 14%
• Ask the clinical pharmacist about suggested recommended alternatives/monitoring
parameters in case of clinically significant drug-drug interactions
107
14.3. Risk Categories for Most common Drugs that Prolong QT and
induce Torsades de Pointes (TdP) (not including all anti-cancer drugs)
Table 7. CredibleMeds Classification of Possible COVID-19 Treatment
Possible COVID-19 Mechanism of CredibleMeds Comment
Treatment action Classification
Antimalarial Drugs The US Food and Drug
Chloroquine Known Risk of Known Risk of Administration Adverse
TdP TdP Event Reporting System
Hydroxchloroquine Known Risk of Known Risk of lists 458 cardiac arrests
TdP TdP suspected to be secondary
Antivirals to the administration of
Lopinavir/Ritonavir Possible Risk of Possible Risk of chloroquine,
TdP TdP hydroxychloroquine,
Adjunct Therapy lopinavir/ritonavir, and
Azithromycin Known Risk of Known Risk of azithromycin individually
TdP TdP
A. Known Risk of TdP

Definition
These drugs prolong the QT interval and are clearly associated with known risk of TdP,
even when taken as recommended.
The most common examples:
Amiodarone, Azithromycin, Chloroquine, chlorpromazine, Cilostazol, ciprofloxacin,
citalopram, Escitalopram, Domeperidone, Donepezil, Erythromycin, Flecainide,
Fluconazole, Haloperidol, Hydroxychloroquine, Levofloxacin, Ondansetron, Propofol,
Sotalol, Terlipressin
B. Possible Risk of TdP
Definition
These drugs can cause QT prolongation but currently lack evidence for a risk of TdP.
The most common are:
108
Betrixaban, Clozapine, Dexmedetomidine, Imipramine (Melipramine),
Lopinavir/Ritonavir, Memantine, Nicardipine, Norfloxacin, Tacrolimus, Tramadol,
Vardenafil, Tamoxifen
C. Conditional Risk of TdP
Definition
These drugs are associated with TdP but under certain conditions of their use (e.g.
excessive dose, in patients with conditions such as hypokalemia, or when taken with
interacting drugs) or by creating conditions that facilitate or induce TdP (e.g by inhibiting
metabolism of a QT prolonging drug or by causing an electrolyte disturbances that induce
TdP).
The most common examples
Amantadine, Amitriptyline, Amphotericin B, Esomeprazole, Famotidine, Fluoxetine,
Furosemide, Hydrochlorothiazide, Indapamide, Metolazone, Ivabradine, Itroconazole,
Ketoconazole, Lansoprazole, Metoclopramide, Metronidazole, Olanzapine, Omeprazole,
Pantoprazole, Paroxetine, Piperacillin/Tazobactam, Propafenone, Quetiapine,
Ranolazine, Resperidone, Sertraline, Torsemide, Voriconazole.
D. Drugs to Avoid in Congenital Long QT
Definition
These drugs pose a high risk of TdP for patients with Congenital long QT (CLQTS)
The most common examples:
All the above plus Albuterol (salbutamol), Amphetamine, Arformoterol, Benzphetamine,
Dobutamine, Dopamine, Fluticasone And Salmeterol, midodrine, Norepinephrine,
Oxymetazoline, Phenylephrine, Phenylpropanolamine, Pseudoephedrine,
Sulfamethoxazole and Trimethoprim, Xylometazoline
109
14.4. QTc monitoting
Relative contraindications (subject to modification based on potential benefits of therapy) to

COVID-19 experimental drugs associated with risk of QT interval prolongation include:
• History of long QT syndrome, or

• Baseline QTc >480 msec (or >510-530 msec if QRS >120 msec), or
• Tisdale risk score ≥11
A. Risk Score For Drug-Associated QTc Prolongation (Tisdale score)
Risk Factors Points

Age ≥68 y 1
Female sex 1
Loop diuretic 1
Serum K+ ≤3.5 mEq/L 2
Admission QTc ≥450 ms 2
Acute MI 2
≥2 QTc-prolonging drugs 3
Sepsis 3
Heart failure 3
One QTc-prolonging drug 3
Maximum Risk Score 21

Risk Levels For Drug-Associated QT Prolongation
Low risk = ≤6 points
Moderate risk = 7-10 points
High-risk = ≥11 points
K+: Potassium;MI:myocardial infarction.
Based on the American college of cardiology Consensus Report about drug interactions
impacting QT interval in a postulated treatment algorithm for COVID-19 :
110
1. Hydroxychloroquine and azithromycin are definite causes of torsade de pointes and are
listed as such at crediblemeds.org. They can provoke proarrhythmia via mechanisms
beyond block of IKr implicated in usual cases of torsade de pointes. There are very limited
data evaluating the safety of combination therapy.
2. The US Food and Drug Administration Adverse Event Reporting System lists 458
cardiac arrests suspected to be secondary to the administration of chloroquine,
hydroxychloroquine, lopinavir/ritonavir, and azithromycin individually.
3. The following interventions may be considered in order to reduce the risk of torsade de
pointes and death:
o Withholding the drugs in patients with baseline QT prolongation (especially QTc
≥500 msec) or with known congenital long QT syndrome.
o Monitoring cardiac rhythm and QT interval and drug withdrawal if QTc exceeds
500 msec.
o Correcting of hypokalemia and hypomagnesemia.
o Avoiding concomitant QTc prolonging agents.
Both the concerns regarding mortality risk, and the intensity of QT and arrhythmia monitoring
should be considered in the context of several important mitigating factors:
1. The duration of use for these medications for COVID-19 infection is short (5 to 10 days
for acute illness).
2. While QT-prolonging medication use has been associated with increased risk of death,
this risk may be smaller than the potential benefit from treatment of COVID-19 for some
patients.
3. There are large potential population-health benefits from hastening viral clearance of
COVID-19.
111
B. Monitoring Algorithm for prevention of drug-induced torsades de pointes or sudden
cardiac death in Coronavirus disease 2019 (COVID-19)
For all Patients before Initiating QT Prolonging Drugs

Tisdale risk score*
Baseline ECG
Electrolytes (Calcium, potassium ,Magnesium)
Renal and hepatic functions
Discontinue other unnecessary QTc-prolonging

Medications and correct electrolyte abnormalities
A B C
Stop all QT If repeated ECG
Prolonging 2-3 hrs after
drugs dosing on day 3
including the shows ∆QTc≥ 30-
COVID-19 60 or QTc≥ 500
drugs if TdP is then go to A
observed If ∆QTc < 60 or
QTc< 500 then
continue
treatment
Interventions
A= Assess/reassess risks and benefits before using. If use is deemed necessary, follow the following:
● Discontinue/avoid other QTc-prolonging medications ● Place on telemetry (or a wearable defibrillator)
● Correct electrolyte abnormalities (K+>4, Mg2+> 2 ● Repeat ECG 2 to 4 hours, 48 hours, and 96 hours after
the1st dose
B=Discontinue other unnecessary QTc-prolonging medications, correct electrolyte abnormalities, and repeat ECG
48 and 96 hours after the first dose
C= Repeat ECG 48 and 96 hours after the first dose
* If Tisdale risk score ≤6, (ECG is not necessary in the setting of limited resources). All patients/ research
subjects should have close monitoring of symptoms with attention to indicators of arrhythmia risk (syncope,
dehydration, initiation of new medications and worsening of health status).
Figure 5. Algorithm for Prevention of Drug-induced Torsades de Pointes or Sudden Cardiac

Death in Coronavirus disease 2019 (COVID-19)
112
14.5. Special Precautions and Monitoring Parameters in Special Populations and
in Patients with Chronic Diseases
• Patients with swallowing Difficulties
• Lopinaver/Ritonavir: Do not crush, use oral solution if unable to swallow tablets (oral
solution should be administered without dilution due to risk of precipitation. Rinse
administration feeding tube with milk not water) Only feeding tubes compatabile with
ethanol and propylene glycol can be used
If oral solution not available, you may use the tablets and doubling
Liponavir/ritonavir to 800/200 with monitoring of ECG
• Favipiravir: Can be crushed and mixed with liquid

• Chloroquine: Crushing not preferred but can be crushed and mixed with Jam or honey
• Hydroxchloroquine: Crushing not preferred but may be crushed and dispersed in water
• Psychotropic medications (Clozapine, Lithium)
Clozapine
• The duration of validity of CBC results depends on the length of time a patient has
been treated with clozapine.
• Patients without symptoms of COVID-19
Patients who are self-isolating should not attend healthcare settings for phlebotomy.
Blood tests should be performed at the patient’s home, using personal protective
equipment and techniques
• Patients with symptoms of COVID-19 Patients
Those presenting with flu-like symptoms: continue clozapine, take an URGENT CBC
(suspect neutropaenia. Act on red or amber results in the usual manner). All patients
should also have a clozapine plasma level taken. Patients presenting with flu-like
symptoms, chest pain and shortness of breath: WITHOLD clozapine (suspect
myocarditis and investigate accordingly)
• Note that if clozapine is withheld for >48h dose retitration is necessary
• Clozapine plasma levels Fever and rises in CRP, indicative of systemic inflammation,
can cause a reduction in the metabolism of clozapine via CYP1A2 liver enzymes.
This results in a rise in clozapine plasma levels. It is possible that infection with
COVID-19 will have this effect. Patients with severe respiratory infection:
113
WITHOLD clozapine until symptoms resolve Patients with mild respiratory
infection: continue clozapine, take a clozapine plasma level (trough level) Be aware
that patients who are unwell may reduce smoking frequency and/or intensity
Smoking
• It significantly reduces the plasma levels of some psychotropic medications. This is
because tobacco smoke contains polyaromatic hydrocarbons which induce hepatic
enzymes, particularly CYP1A2. Stopping smoking will normalise enzyme activity
and cause plasma levels of some drugs to rise over a week or so. Dose reduction will
be necessary to avoid drug toxicity. Note that nicotine replacement therapy, including
e-cigarettes, has no effect on hepatic enzymes – switching from tobacco smoking to
other forms of nicotine has the same effect as stopping smoking. Clinicians should
assume that smoking will reduce to some extent in patients with respiratory infection
and take action accordingly.
• Special considerations in Critically ill patients.
• Seriously ill patients often have comorbidities that can increase risk of serious
arrhythmias. These include:
o Hypokalemia
o Hypomagnesemia
o Fever
• Mechanisms to minimize arrhythmia risk Seriously ill patients and patients with
cardiovascular disease, in include, See Fgure 5.
o Electrocardiographic/QT interval monitoring:
▪ Withhold the drugs in patients with baseline QT prolongation (eg, QTc ≥500 msec) or
with known congenital long QT syndrome.
▪ o Monitor cardiac rhythm and QT interval; withdrawal of the drugs if QTc exceeds a
preset threshold of 500 msec.
▪ In patients critically ill with COVID-19 infection, frequent caregiver contact may
need to be minimized, so optimal electrocardiographic interval and rhythm monitoring
may not be possible.
▪ Correction of hypokalemia to levels of >4 mEq/L and hypomagnesemia to levels of >2
mg/dL.
▪ Avoid other QTc prolonging agents whenever feasible
• Patients with cardiovascular disease (See QT monitoring Protocol in section 14)
114
• Diabetic patients (Close monitoring of glucose level throughout the disease especially for
patients on Chloroquine or hydroxychloroquine )
115
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MANAGEMENT

11- Guidelines for STEMI 63

GFR Glomerular Filtration Rate

1.2. General advice

1.5. Use of drugs during pregnancy and lactation

Levofloxacin Category C Monitor infant for

2.1. Children at increased risk of COVID-19 complications

2.2. Assessment of children in COVID-19 pandemic

2.3. Emergency Department

2.4. Clinical Manifestations of COVID-19 in Children

2.6. Medications in Children suspected to have COVID-19

2.7. Vaccination in Children suspected to have COVID-19

2.8. Neonatal Management for 2019 Novel Coronavirus Infection

• Exclusive breastfeeding should continue for 6 months with timely introduction of

• Breastfeeding counselling, basic psychosocial support, and practical feeding support

Contact & Droplet Precautions

Room-in with Mother who can look after neonate

- Monitor neonate for symptoms

Mother COVID-19 Mother COVID-19 positive

3.2. Management of elective and semi-elective paediatric out-patient

3.3. Management of paediatric otolaryngological emergencies

3.4. Management of children with tracheostomy

3.5. Sick neonates

>23 to 40 kg: Oral: 60 mg twice daily.

>40 kg: Oral: 75 mg twice daily.

C. Patients with evidence of mild COVID-19 pneumonia (oxygen saturation 94-95% in

b. Not high-risk patient (as defined above):

c. If starting anti-retroviral (Lopinavir/Ritonavir) treatment is thought to be life

5.1. Suspected Cases

• Management Protocol for Dialysis Patients Suspected to have COVID-19 Infection is

5.5. Peritoneal Dialysis

5.8. CYTOKINES MOLECULAR WEIGHT

If the patient is suspicious. Proceed

HRCT Chest & Chest Consultation

CT appearance CT appearance non- Normal

Nasopharyngeal swab for Laboratory Tests suggestive of

Routine dialysis in isolation

Repeat Repeat CT Chest after

Nasal pressure, 15 minutes

Bleeding continues: Bleeding cessation:

8.1. Mastoid Surgery

8.2. Other Otology Procedures

8.3. Necrotising Otitis Externa:

Initial treatment regime

CBC, liver functions, Kidney Functions, CRP, Glandular fever screen

Observe for 3-4 hours

● Cardiopulmonary exercise testing for functional assessment (outpatient and

● In-person cardiovascular implantable electronic device (CIED)

Table 5. Risk Score For Drug-Associated QTc Prolongation

Risk Factors Points

Suggested Monitoring For Outpatient Clinical Use

Clinical Cardiovascular Concerns in COVID-19 Illness

Myocarditis and acute heart Failure in COVID 19

14.1. Summary of Recommendations for Dosing and Monitoring of the

GFR ≥10 mL/minute: No dosage adjustment necessary.

GFR <10 mL/minute: Administer 50% of dose.

Continuous renal replacement therapy (CRRT): No dosage adjustment necessary.