COVID

essentials
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 COVID 19

Index
Sl.No. Chapter Pg.No.
1. Preventive & Social Medicine 09
2. Microbiology 34
3. Pathology 37
4. Biochemistry 44
5. Medicine 50
6. Radiology 60
7. Pharmacology 66
8. Anaesthesia 89
9. Surgery 93
10. ENT 95
11. Ophthalmology 101
12. OBGY 103
13. Paediatrics 108
14. Psychiatry 115
 9

Preventive & Social Medicine

History
The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral
infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2),
which emerged in Wuhan, China and spread around the world in 2019.
Previous Outbreaks
Severe acute respiratory syndrome (SARS) outbreak caused by
SARS-CoV, 2002 in Guangdong, China
Key reservoir of infection : Bat, raccoon dogs and palm civets

Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak

caused an endemic in Middle Eastern countries (Saudi Arabia) in 2012
Key reservoir of infection : Camels

Reference: https://www.hkmj.org/abstracts/v21n5/478.htm

Transmission

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113610/#!po=8.92857

.
 10

direct indirect
(1) Transmission via aerosols formed via (1) Fomites or surfaces (e.g.,
surgical and dental procedures and/or in the furniture and fixtures) present
form of respiratory droplet nuclei; within the immediate environment
(2) Body fluids and secretions (feces, saliva, of an infected patient and
urine, semen, and tears) (2) Objects used on the infected
(3) mother-to-child. person (e.g., stethoscope or
thermometer).
Mode of transmission
The disease is mainly transmitted via the respiratory route when people inhale
droplets and particles that infected people release as they breathe, talk, cough,
sneeze, or sing
After people are infected with COVID-19, they are able to transmit the
disease to other people from one to three days before developing symptoms,
known as presymptomatic transmission.
People are most infectious when they show symptoms, even if mild or non-
specific, as the viral load is highest at this time.
They remain infectious, on average, seven to twelve days in moderate cases, and
two weeks in severe cases.
People who are completely asymptomatic are able to transmit the virus.
A person can get COVID-19 by touching a surface or object that has the virus on it
(fomite), and then touching their own mouth, nose, or eyes,but it is not the main
mode of transmission.

Reference: www.rehva.eu
Reference: https://en.m.wikipedia.org/wiki/Transmission_of_COVID-19
 11

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461745/

https://en.m.wikipedia.org/wiki/Transmission_of_COVID-19#/media/File%3ACovid-19_Aerosol.jpg

The incubation period for COVID-19 is thought to

Q. The most common mode
extend to 14 days, with a median time of 4-5 days
of transmission in COVID 19?
from exposure to symptoms onset.
 12

Corona Variants

WHO label Pango lineages Earliest documented samples

Alpha B.1.1.7 United Kingdom, Sep-2020

B.1.351
Beta
B.1.351.2
South Africa, May-2020 Lambda variant,
B.1.351.3 also known as
lineage C.37, is a
Gamma P.1 Brazil, Nov-2020 variant of SARS-
P.1.1 CoV-2, the virus
P.1.2 that causes
COVID-19. It was
Delta B.1.617.2 India, Oct-2020 first detected in
AY.1 Peru in December
AY.2 2020.
Reference:https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/

https://malaysia.news.yahoo.com/contagious-concerning-know-covid-19-150014916.html
 13
Double Mutant strain in India

WHO calls the

Indian variant of
SARS-CoV2 as
‘Varient of
global concern’.

The double mutation in India is a variant carrying both the L452R and E484Q
mutations seen in spike protein.
Both of these are able to evade detection by the immune system.
The double mutant strain of Coronavirus has been named B.1.617.
- Highly contagious
- Escape immune defence
- Increased severity
- Vaccine efficiency decreased (reduced serum antibody binding & neutralisation)
L452R mutant: increases 20% transmission
E484Q: also known as escape mutation

“Delta Plus”: Sub-

lineage of the
Delta variant has
acquired the
spike protein
mutation called
K417N which is
also found in the
Beta variant first
identified in South
Africa.

Q. What is the
variants seen in
double mutant
strain in India
and the mutation
occurs in which
part of the
Corona virus?
 14

Biomedical waste management

Schematic of the BMW/hospital waste generation to disinfection and disposal practices.

Q. How is the personal protective

materials used in Covid-19 ward
segregated and disposed?
 15

Common Bio-Medical Waste Treatment Facility (CBMWTF)

https://health.uk.gov.in/files/Corona/13._Biomedical_Waste_Management_for_COVID_19_1.pdf
 16

Covid-19 prevention

Masks for protection

Masks are a key measure to suppress transmission and save lives.
Masks should be used as part of a comprehensive ‘Do it all!’ approach including
physical distancing, avoiding crowded, closed and close-contact settings, good
ventilation, cleaning hands, covering sneezes and coughs, and more.
Depending on the type, masks can be used for either protection of healthy persons
or to prevent onward transmission.
Fabric masks should be made of three layers of fabric:
• Inner layer of absorbent material, such as cotton.
• Middle layer of non-woven non-absorbent material, such as polypropylene.
• Outer layer of non-absorbent material, such as polyester or polyester blend

• Clean your hands before you put your mask on, as well as before and after
you take it off, and after you touch it at any time.
• Make sure it covers both your nose, mouth and chin.
• When you take off a mask, store it in a clean plastic bag, and every day either
wash it if it’s a fabric mask, or dispose of a medical mask in a trash bin.
• Don’t use masks with valves.
 17

WHO provides the following guidance on the

correct use of masks:
• Perform hand hygiene before putting on the mask.
• Inspect the mask for tears or holes, and do not use a damaged mask.
• Place the mask carefully, ensuring it covers the mouth and nose, adjust to the nose
bridge and tie it securely to minimize any gaps between the face and the mask. If
using ear loops, ensure these do not cross over as this widens the gap between the
face and the mask.
• Avoid touching the mask while wearing it. If the mask is accidently touched, perform
hand hygiene.
• Remove the mask using the appropriate technique. Do not touch the front of the
mask, but rather untie it from behind.
• Replace the mask as soon as it becomes damp with a new clean, dry mask.
• Either discard the mask or place it in a clean plastic resealable bag where it is kept
until it can be washed and cleaned. Do not store the mask around the arm or wrist or
pull it down to rest around the chin or neck.
• Perform hand hygiene immediately afterward discarding a mask.
• Do not re-use single-use mask.
• Discard single-use masks after each use and properly dispose of them immediately
upon removal.
• Do not remove the mask to speak.
• Do not share your mask with others.
• Wash fabric masks in soap or detergent and preferably hot water (at least 60°
Centigrade/140° Fahrenheit) at least once a day. If it is not possible to wash the
masks in hot water, then wash the mask in soap/detergent and room temperature
water, followed by boiling the mask for 1 minute.

Reference: Mask use in the context of COVID-19 Interim guidance 1 December 2020, WHO
 18
Mask use in health care settings depending on transmission
scenario, target population, setting, activity and type*

Reference: Mask use in the context of COVID-19 Interim guidance 1 December 2020, WHO
 19
Mask use in community settings depending on transmission
scenario, setting, target population, purpose and type*

Reference: Mask use in the context of COVID-19 Interim guidance 1 December 2020, WHO
20
21
 22
Hand washing
WHEN TO WASH HANDS TO
PREVENT COVID-19:
After blowing your nose,
coughing, or sneezing.
After being in a public place
Before and after caring for
someone who is sick

Hand sanitizer
Alcohol-based hand sanitizers
can quickly reduce the number
of microbes on hands in some
situations, but sanitizers do not
eliminate all types of germs.

Hand hygiene must be ensured following contact with ill person or his immediate
environment.
Hand hygiene should also be practiced before and after preparing food, before eating,
after using the toilet, and whenever hands look dirty.
Use soap and water for hand washing at least for 40 seconds. Alcohol-based hand rub can
be used, if hands are not visibly soiled.
After using soap and water, use of disposable paper towels to dry hands is desirable. If
not available, use dedicated clean cloth towels and replace them when they become wet.
Perform hand hygiene before and after removing gloves
 23
Hand washing technique

Donning PPE (Putting on) Doffing PPE (Taking off)

1 Perform hand hygiene 1 Remove shoe covers
2 Put on shoe covers 2 Remove gown and gloves together
3 Put on gown 3 Perform hand hygiene
4 Put on mask/respirator 4 Remove eye protection
5 Put on eye protection 5 Remove mask/respirator
6 Put on gloves 6 Perform hand hygiene
 24

Steps in Wearing PPE (Donning)

Steps in Removing PPE (Doffing)

 25

Bassoon
 26

poohed
 27

Patients eligible for home isolation

i. The patient should be clinically assigned as mild/ asymptomatic

case by the treating Medical Officer.

ii. Such cases should have the requisite facility at their residence for
self-isolation and for quarantining the family contacts.

iii. A care giver should be available to provide care on 24 x7 basis. A

communication link between the caregiver and hospital is a
prerequisite for the entire duration of home isolation.

iv. Elderly patients aged more than 60 years and those with co-morbid
conditions such as Hypertension, Diabetes, Heart disease, Chronic lung/
liver/ kidney disease, Cerebro-vascular disease etc shall only be allowed
home isolation after proper evaluation by the treating medical officer.
v. Patients suffering from immune compromised status (HIV,
Transplant recipients, Cancer therapy etc.) are not recommended for
home isolation and shall only be allowed home isolation after proper
evaluation by the treating medical officer.

Instructions for the patient

i. Patient must isolate himself from other household members.
ii. The patient should be kept in a well-ventilated room with cross ventilation.
iii. Patient should at all times use triple layer medical mask. Discard mask after 8 hours of
use or earlier if they become wet or visibly soiled after disinfecting it with 1% Sodium
Hypochlorite.
v. Patient must take rest and drink lot of fluids to maintain adequate hydration.
vi. Follow respiratory etiquettes at all times.
vii. Frequent hand washing with soap and water or clean with alcohol-based sanitizer.
viii. Don’t share personal items with other people in the household.
ix. Ensure cleaning of surfaces in the room that are touched often (tabletops, doorknobs,
handles, etc.) with 1% hypochlorite solution.
x. Self-monitoring of blood oxygen saturation with a pulse oximeter and daily temperature
monitoring is strongly advised.

https://www.mohfw.gov.in/pdf/RevisedguidelinesforHomeIsolationofmildasymptomaticCOVID19cases.pdf
28
 29

Infection Prevention and Control Practices

 30

https://www.mohfw.gov.in/pdf//National%20Guidelines%20for%20IPC%20in%20HCF%20- %20final%281%29.pdf
 31

First Wave vs Second wave

32
33
 34

Microbiology

Coronaviruses belong to the Coronaviridae family in the Nidovirales order.

Corona represents crown-like spikes on the outer surface of the virus; thus, it was
named as a coronavirus.
Coronaviruses are minute in size (65–125 nm in diameter) and contain a single-
stranded RNA as a nucleic material
Coronavirus virions are spherical to
pleomorphic enveloped particles.
The envelope is studded with projecting
glycoproteins, and surrounds a core
consisting of matrix protein enclosed within
which is a single strand of positive-sense
RNA associated with nucleoprotein.
The envelope glycoproteins are responsible
for attachment to the host cell and also
carry the main antigenic epitopes,
particularly the epitopes recognized by
neutralizing antibodies.
Electron micrograph showing human coronavirus
OC43 also possesses a haemagglutin.
 35

First Covid WHO declared the novel

First Covid case WHO declared
case in coronavirus outbreak a First Covid 19 First lockdown
identified in COVID-19 outbreak a
Kerala, Public Health Emergency death in India in India
Wuhan China global pandemic
India of International Concern

Dec 18, 2019 Jan 27, 2020 Jan 30, 2020 March 11, 2020 March 12, 2020 March 24, 2020 October Delta
20 variant
20 identified
March 8, 2021 March 2021 Jan 16, 2021 in India

First Death in India Second wave Vaccination

Due to COVID-19 in India begins in
Vaccination India

Q. Which is the structural protein responsible

for binding of host cell receptors?
 36
life cycle of SARS-CoV-2 in host cells

ACE2, angiotensin-converting enzyme 2; ER, endoplasmic reticulum; ERGIC, ER–Golgi intermediate compartment.

S protein binds to the cellular receptor ACE2

Conformation change in the S protein facilitates viral envelope

fusion with the cell membrane through the endosomal pathway.

SARS-CoV-2 releases RNA into the host cell

Genome RNA is translated into viral replicase polyproteins pp1a and 1ab,
which are then cleaved into small products by viral proteinases.

The polymerase produces a series of subgenomic mRNAs by discontinuous

transcription and finally translated into relevant viral proteins.

Viral proteins and genome RNA are subsequently assembled into virions in the
ER and Golgi and then transported via vesicles and released out of the cell.

Reference: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7113610/#!po=8.92857
 37

Pathology
Pathogenesis of SARS-CoV-2
SARS-CoV-2 is composed of four main structural proteins along with 16
nonstructural proteins, and 5-8 accessory proteins.
spike (S), nucleocapsid (N),
envelope (E) glycoprotein, membrane (M) protein,

Amino (N)-terminal S1 subunit

Receptor-binding domain (RBD)
Binding site for the human angiotensin-converting
enzyme 2 (ACE2) receptors.
surface spike N-terminal domain (NTD)
(S) glycoprotein Facilitates viral entry into the host cell.
Potential target for neutralization in response to antisera
or vaccines.
Carboxyl (C)-terminal S2 subunit
Fusion peptide,

1
Responsible
for virus-cell
Transmembrane domain, membrane
Cytoplasmic domain fusion

Pathogenesis of SARS-CoV-2-induced Pneumonia

SARS-CoV-2 gains entry into the hosts' cells by binding the SARS-CoV-2 spike or
S protein (S1) to the ACE2 receptors abundantly on respiratory epithelium such
as type II alveolar epithelial cells.
early phase
Characterized by viral replication resulting in direct virus-mediated tissue
damage.
late phase
Infected host cells trigger an immune response with the recruitment of T
lymphocytes, monocytes, and neutrophil recruitment which releases cytokines
such as:
Tumor necrosis factor-α (TNF α), Interleukin-6 (IL-6),
Granulocyte-macrophage colony- IL-1β, IL-8, IL-12
stimulating factor (GM-CSF), Interferon (IFN)-γ.
Interleukin-1 (IL-1),

www.ncbi.nlm.nih.gov
 38

severe COVID-19

Immune system's overactivation

'cytokine storm' characterized by the release of high

levels of cytokines, especially IL-6 and TNF-α

Local and systemic inflammatory response.

Increased vascular permeability and pulmonary edema is due to

a) Endotheliitis as a result of direct viral injury and perivascular inflammation

leading to microvascular and microthrombi deposition
b) Dysregulation of the RAAS due to increased binding of the virus to the ACE2
receptors
c) Activation of the kallikrein- bradykinin pathway, the activation of which
enhances vascular permeability,
d) Enhanced epithelial cell contraction causing swelling of cells and disturbance
of intercellular junctions.
Binding of SARS-CoV-2 to the Toll-Like Receptor (TLR) induces the release of
pro-IL-1β, which is cleaved into the active mature IL-1β that mediates lung
inflammation, until fibrosis.
Effect of SARS-CoV-2 on Extrapulmonary Organ Systems
SARS-CoV-2–induced organ dysfunction affects gastrointestinal tract (GI),
hepatobiliary, cardiovascular, renal, and central nervous system due to the following
mechanism:
Direct viral toxicity,
Ischemic injury caused by vasculitis, thrombosis, or thrombo- inflammation,
Immune dysregulation,
Renin-angiotensin-aldosterone system (RAAS) dysregulation

RBD is a fundamental peptide domain in the

pathogenesis of infection- binding site for
ACE2 receptors

www.ncbi.nlm.nih.gov
 39
hypercoagulable state with COVID-19
COVID-19 Severe inflammatory response in alveoli
Release of inflammatory cytokines

Activation of epithelial cells, monocytes and macrophages

Direct infection of the endothelial cells through the ACE2 receptor

also leads to endothelial activation and dysfunction, expression of TF,
and platelet activation and increased levels of VWF and FVIII

Thrombin generation Fibrin clot formation.

Inflammation through its Activates endothelium through

effect on platelets and the PAR receptor, which leads
promote NET formation to release of C5A that further
in neutrophils activates monocytes.

www.ncbi.nlm.nih.gov
 40

PATHOGENESIS OF COVID – 19 AND THE NEED FOR ANTICOAGULATION

 41

D-dimer
D-dimer is a fibrin degradation product that is often used to measure
and assess clot formation.
Patients with severe COVID-19 have a higher level of D-dimer than those with
non-severe disease,
D-dimer greater than 0.5 µg/ml is associated with severe infection in patients
with COVID-19.

Blood test done in COVID-19

D-dimer To identify thrombotic activity < 500 ng/mL

C- Reactive Protein To detect the presence of Up to 6 mg/L

inflammation or an infection
Procalcitonin To assess the risk of 0.15 ng/mL or less
bacterial co-infection

Ferritin To assess intracellular 20- 336 ng/mg

iron storage

Interleukin- 6 To identify rapid 0- 16.4 pg/mL

disease progression

Diffuse alveolar damage in COVID-19

1. Corona virus infects type 2
pneumocytes
2. Immune cells including macrophages
identify the virus and produce cytokines
3. Cytokines attract more immune cells
such as WBC, which inturn produce
more cytokines, creating a cycle of
inflammation that damages lung cells
4. Damage can occur through the
formation of fibrin
5. Increases capillary permeability
leading to interstitial and alveolar
edema
 42
Histopathology of Covid 19 infection
Lungs: Typical diffuse alveolar damage, Presence of type II pneumocyte
hyperplasia, airway inflammation, and hyaline membranes in alveolar zones
Brain: Acute hypoxic injury in all patients' cerebrum and cerebellum.

Heart: Presence of SARS-CoV-2 viral genome within the myocardium

Kidney: Diffuse proximal tubular injury with loss of brush border, non-isometric
vacuolar degeneration, and necrosis. Electron microscopy showed clusters of
coronavirus-like particles with spikes in the tubular epithelium and podocytes.
GI Tract: Positive staining of the viral nucleocapsid protein in the gastric,
duodenal, and rectal epithelium cytoplasm. Numerous infiltrating plasma cells and
lymphocytes with interstitial edema were seen in the lamina propria of the stomach,
duodenum, and rectum.
Liver: Hepatic steatosis, Chronic congestion, Hepatocyte necrosis,
Nodular proliferation.

Diffuse alveolar damage

Acute lung injury with intra-alveolar hyaline

Patchy intra-alveolar plugs of fibrin and interstitial
membranes, fibrin plugs and interstitial inflammation.
inflammation.

Thrombus within a small vessel in a lung

Endothelialitis and acute lung injury. resection of a COVID-19 patient.
www.ncbi.nlm.nih.gov
 43

pathological features of COVID-19

Biopsy samples were taken from lung, liver, and heart tissue of a patient
who died of Covid 19.

The right lung showed evident desquamation of pneumocytes and hyaline membrane
formation, indicating acute respiratory distress syndrome (A). The left lung tissue
displayed pulmonary oedema with hyaline membrane formation, suggestive of early-phase
ARDS (B). Interstitial mononuclear inflammatory infiltrates, dominated by lymphocytes,
were seen in both lungs. Multinucleated syncytial cells with atypical enlarged pneumocytes
characterised by large nuclei, amphophilic granular cytoplasm, and prominent nucleoli
were identified in the intra-alveolar spaces, showing viral cytopathic-like changes.

The liver biopsy specimens of the patient with COVID-19 showed moderate
microvesicular steatosis and mild lobular and portal activity (C), indicating the injury
could have been caused by either SARS-CoV-2 infection or drug-induced liver injury.
There were a few interstitial mononuclear inflammatory infiltrates, but no other
substantial damage in the heart tissue (D).

https://www.thelancet.com/
 44

Biochemistry
Sample collection
Preferred sample
Throat and nasal swab in viral transport media (VTM) and transported in cold
chain.
Alternate
Nasopharyngeal swab, BAL or endotracheal aspirate which has to be mixed
with the viral transport medium and transported in cold chain.

General guidelines
• Use appropriate PPE for specimen collection (droplet, airborne and contact
precautions for URT specimens; airborne precautions using full PPE for LRT
specimens). Maintain proper infection control when collecting specimens.
• Restricted entry to visitors or attendants during sample collection.
• Complete the requisition form for each specimen submitted.
• Proper disposal of all waste generated.

Oropharyngeal swab:
Tilt patient’s head back 70 degrees. Rub swab over both tonsillar pillars and
posterior oropharynx and avoid touching the tongue, teeth, and gums. Use
only synthetic fiber swabs with plastic shafts. Do not use calcium alginate
swabs or swabs with wooden shafts. Place swabs immediately into sterile tubes
containing 2-3 ml of viral transport media.

Nasopharyngeal swab:
Tilt patient’s head back 70 degrees. Insert flexible swab through the nares
parallel to the palate (not upwards) until resistance is encountered or the
distance is equivalent to that from the ear to the nostril of the patient.
Gently, rub and roll the swab.
Leave the swab in place for several seconds to absorb secretions before
removing.
 45

Test for COVID-19

diagnostic tests antibody tests

Antibody tests look for antibodies in
Molecular and antigen tests are
your immune system produced in
types of diagnostic tests than
response to SARS-CoV-2, the virus
can detect if you have an active
that causes COVID-19.
COVID-19 infection.

https://www.fda.gov/consumers/consumer-updates/coronavirus-disease-2019-testing-basics
 46

The time relationship between viral load, symptoms and positivity on diagnostic tests.
The onset of symptoms (day 0) is usually 5 days after infection (day –5).
At this early stage corresponding to the window or asymptomatic period, the viral load
could be below the RT-PCR threshold and the test may give false-negative results.
The same is true at the end of the disease, when the patient is recovering.
Seroconversion may usually be detectable between 5–7 days and 14 days after the
onset of symptoms; therefore, in the first phase of the disease, the serological tests
are more likely to give false-negative results.
The dotted black line in the graph illustrates the sensitivity of the chemiluminescent
assay .
Nucleic Acid Amplification Test
A Nucleic Acid Amplification Test, or NAAT, is a type of viral diagnostic test for
SARS-CoV-2, the virus that causes COVID-19.
NAATs detect genetic material (nucleic acids). NAATs for SARS-CoV-2 specifically
identify the RNA (ribonucleic acid) sequences that comprise the genetic material
of the virus.
NAATs can use many different methods to amplify nucleic acids and detect the virus:
Reverse transcription polymerase chain reaction (RT-PCR)
Isothermal amplification including:
Nicking endonuclease amplification reaction (NEAR)
Transcription mediated amplification (TMA)
Loop-mediated isothermal amplification (LAMP)
Helicase-dependent amplification (HDA)
Clustered regularly interspaced short palindromic repeats (CRISPR)
Strand displacement amplification (SDA)

https://www.cdc.gov/coronavirus/2019-ncov/lab/naats.html
 47

Molecular Testing
The standard diagnostic mode of testing is testing a nasopharyngeal swab for SARS-
CoV-2 nucleic acid using a real-time PCR assay.
Commercial PCR assays have been validated by the US Food and Drug Administration
(FDA) with emergency use authorizations (EUAs) for the qualitative detection of
nucleic acid from SARS-CoV-2 from specimens obtained from nasopharyngeal swabs
as well as other sites such as oropharyngeal, anterior/mid- turbinate nasal swabs,
nasopharyngeal aspirates, bronchoalveolar lavage (BAL) and saliva.
The collection of BAL samples should only be performed in mechanically ventilated
patients as lower respiratory tract samples seem to remain positive for a more
extended period.
The sensitivity of PCR testing is dependent on multiple factors that include the
adequacy of the specimen, technical specimen collection, time from exposure, and
specimen source.
SARS-CoV-2 antigen tests are less sensitive but have a faster turnaround time
compared to molecular PCR testing. Comprehensive testing for other respiratory
viral pathogens should be considered for appropriate patients as well.
Rapid serological tests
For the rapid detection of SARS-CoV-2 antibodies (IgG and IgM).
Cheap to manufacture, store and distribute.
The rapid POC immunoassays are generally LFIA.
In lateral flow assays, a membrane strip is coated with two lines: gold nanoparticle–
antibody conjugates are located on one line and bind antibodies on the other.
The blood sample from the patient is put on the membrane, and the proteins are drawn
through the membrane strip by capillary action. As it passes the first line, the antigen
binds to the gold nanoparticle–antibody conjugate, and the complex flows across the
membrane.
An antibody test can evaluate for the presence of antibodies that occurs as a result
of infection.
Serologic testing has limitations in specificity and sensitivity.
Antibody testing may be instrumental in broad-based surveillance of COVID-19 and
evaluate the immunity conferred from infection or vaccination.
 48

Advisory for COVID-19 Home Testing using Rapid Antigen Tests

(RATs)
Home testing by RAT is advised only in symptomatic individuals and immediate contacts
of laboratory confirmed positive cases.
Indiscriminate testing is not advised.
Home testing should be conducted as per the procedure described by the manufacturer
in the user manual.
The home testing mobile app is available in Google playstore and Apple store and must
be downloaded.
The mobile app is a comprehensive guide of the testing procedure and will provide a
positive or negative test result to the patient.
All users are advised to click a picture of the test strip after completing the test
procedure with the same mobile phone which has been used for downloading the mobile
app and user registration.
Data in the app of your mobile phone will be centrally captured in a secure server which
is connected with the ICMR COVID-19 testing portal, where all data will be eventually
stored.
Patient confidentiality will be fully maintained.
All individuals who test positive may be considered as true positives and no repeat
testing is required.
All test positive individuals are advised to follow home isolation and care as per the ICMR
& Ministry of Health & Family Welfare (MoH&FW) protocol.
All symptomatic individuals who test negative by RAT should get themselves
immediately tested by RTPCR. This is especially important as the RATs are likely to
miss few positive cases presenting with a low viral load.
All RAT negative symptomatic individuals may be treated as suspect COVID-19 cases and
are advised to follow the ICMR/MoH&FW home isolation protocol while awaiting the
RTPCR test result.
All results may be interpreted as per the protocol laid down by the manufacturer in the
user manual.
Manufacturer’s instructions must be strictly followed for disposal of the test kit, swab
and other materials.
 49

Laboratory investigation for proven COVID 19 patients

 50

Medicine
Case definition
Suspect case
A. A person who meets the clinical AND epidemiological criteria:
Clinical Criteria:
• Acute onset of fever AND cough; OR
• Acute onset of ANY THREE OR MORE of the following signs or symptoms: Fever,
cough, general weakness/ fatigue, headache, myalgia, sore throat, coryza, dyspnoea,
anorexia/nausea/vomiting, diarrhoea, altered mental status.
AND
Epidemiological Criteria:
• Residing or working in an area with high risk of transmission of virus: closed
residential settings, humanitarian settings such as camp and camp-like settings for
displaced persons; any time within the 14 days prior to symptom onset; or
• Residing or travel to an area with community transmission any time within the 14
days prior to symptom onset; or
• Working in any healthcare setting, including with in health facilities or within the
community; any time within the 14 days prior of symptom onset.
B. A patient with severe acute respiratory illness:
(SARI: acute respiratory infection with history of fever or measured fever of ≥38
C°; and cough; with onset within the last 10 days; and requires hospitalization).

Probable case
A. A patient who meets clinical criteria above AND is a contact of a probable or
confirmed case, or linked to a COVID-19 cluster
B. A suspect case with chest imaging showing findings suggestive of COVID-19
disease
C. A person with recent onset of anosmia(loss of smell) or ageusia(loss of taste)
in the absence of any other identified cause.
D. Death, not otherwise explained, in an adult with respiratory distress preceding
death AND was a contact of a probable or confirmed case or linked to a COVID-19
cluster.

www.icmr.gov.in
 51

Confirmed case
A. A person with a positive Nucleic Acid Amplification Test (NAAT) including RT-
PCR or any other similar test approved by ICMR.
B. A person with a positive SARS-CoV-2 Antigen-RDT AND meeting either the
probable case definition or suspect criteria OR
C. An asymptomatic person with a positive SARS-CoV-2 Antigen-RDT who is a
contact of a probable or confirmed case.

Clinical Features
• Fever,
• cough,
• general weakness/ fatigue,
• headache,
• myalgia,
• sore throat, coryza,
• dyspnoea,
• anorexia/nausea/vomiting,
• diarrhoea,
• altered mental status.
• Loss of smell (anosmia) or loss of taste (ageusia) preceding the onset of
respiratory symptoms has also been reported Loss of smell has been shown to
increase the pre-test probability of presence of SARS-COV-2.
Older people and immune-suppressed patients in particular may present with
atypical symptoms such as fatigue, reduced alertness, reduced mobility,
diarrhoea, loss of appetite, delirium, and absence of fever. Children might not
have fever or cough as frequently as adults.

Risk factors
• Age more than 60 years
• Underlying non-Communicable diseases like cardiovascular disease,
hypertension, and CAD, DM (Diabetes Mellitus) and other
immunocompromised states, Chronic lung/kidney/liver disease,
Cerebrovascular diseases and Obesity

www.icmr.gov.in
 52
five tier system of COVID care

Categories based on symptomatology

Category A
Mild sore throat / cough / rhinitis /diarrhea
Category B

Fever and/or severe sore throat / cough

OR
Category-A with any one of the following risk factors
• Lung/ heart / liver/ kidney / neurological disease/ Hypertension/
haematological disorders/ uncontrolled diabetes/ cancer /HIV- AIDS
• On long term steroids
• Pregnant lady
• Age –more than 60 years.
Category C
Breathlessness, chest pain, drowsiness, fall in blood pressure, haemoptysis,
cyanosis [red flag signs]
Children with ILI (influenza like illness) with red flag signs
(Somnolence, high/persistent fever, inability to feed well, convulsions,
dyspnoea /respiratory distress, etc).
Worsening of underlying chronic conditions

Categorization should be reassessed

every 24-48 hours for Category A & B
 53

Clinical Severity Stages

 54
CLINICAL GUIDANCE FOR MANAGEMENT OF ADULT COVID-19 PATIENTS

*High-risk for severe disease or mortality

✓ Age>60years ✓ Chronic lung/kidney/liver disease
✓ Cardiovascular disease, hypertension, and CAD ✓ Cerebrovascular disease
✓ DM (Diabetes mellitus) and other ✓ Obesity
immunocompromised states

www.icmr.gov.in
 55

Awake proning
Should be encouraged in all patients who require supplemental oxygen
Criteria to be fulfilled
• Normal mental status
• Able to self-prone or change position with minimal assistance
Avoid proning
• Hemodynamic instability Early self-proning in awake, non-
intubated patients.
• Close monitoring not possible
• Any COVID-19 patient with respiratory embarrassment severe enough to be
admitted tothehospitalmaybeconsideredforrotationandearlyself- proning.
• Care must be taken to not disrupt the flow of oxygen during patient rotation
• Typical protocols include 30–120 minutes in prone position, followed by 30–120
minutes in left lateral decubitus, right lateral decubitus, and upright sitting
position.

acute respiratory distress syndrome

Severe new-onset respiratory failure or worsening of an already identified
respiratory picture.
The diagnosis requires a set of clinical and ventilatory criteria such as chest
imaging utilized includes chest radiograph, CT scan, or lung ultrasound
demonstrating bilateral opacities (lung infiltrates > 50%), not fully explained by
effusions, lobar, or lung collapse.
If there are clinical and radiologic findings of pulmonary edema, heart failure, or
other causes such as fluid overload, they should be excluded before assessing it to
be ARDS.
The Berlin definition classifies ARDS into three types based on the degree of
hypoxia, with the reference parameter being PaO2/FiO2 or P/F ratio
Mild ARDS: 200 mmHg < PaO2/FiO2 ≤ 300 mmHg in patients not receiving
mechanical ventilation or in those managed through non-invasive ventilation
(NIV) by using positive end-expiratory pressure (PEEP) or a continuous positive
airway pressure (CPAP) ≥ 5 cmH2O.
Moderate ARDS: 100 mmHg < PaO2/FiO2 ≤ 200 mmHg
Severe ARDS: PaO2/FiO2 ≤ 100 mmHg.

www.ncbi.nlm.nih.gov
 56

Requirements for safe prone positioning in ARDS

• Start proning if P/F ratio <150 while being ventilated with FiO2 >0.6 and PEEP
>5 cm H2O
• Pre-oxygenate the patient with FiO2 1.0
• Secure the endotracheal tube and arterial and central venous catheters
• Adequate number of staff to assist in the turn and to monitor the turn
• Supplies to turn (pads for bed, sheet, protection for the patient)
• Knowledge of how to perform the turn as well as how to supine the patient in
case of an emergency.
Contraindications to prone ventilation
• Spinal instability requires special care
• Intra cranial pressure may increase on turning

Extrapulmonary Manifestations
Renal manifestations:
Patients hospitalized with severe COVID-19 are at risk for developing kidney injury,
most commonly manifesting as acute kidney injury (AKI), which is likely
multifactorial in the setting of hypervolemia, drug injury, vascular injury, and
drug-related injury, and possibly direct cytotoxicity of the virus itself.
AKI is the most frequently encountered extrapulmonary manifestation of
COVID-19 and is associated with an increased risk of mortality.
Other clinical and laboratory manifestations include proteinuria, hematuria,
electrolyte abnormalities such as hyperkalemia, hyponatremia, acid- base balance
disturbance such as metabolic acidosis

Cardiac manifestations:
Myocardial injury manifesting as myocardial ischemia/infarction (MI) and
myocarditis are well-recognized cardiac manifestations in patients with COVID-19.
Other common cardiac manifestations include ACS, arrhythmias, cardiomyopathy, and
cardiogenic shock.
Patients with elevated troponin levels have more frequent malignant arrhythmias and
a high mechanical ventilation rate than patients with normal troponin levels.
Acute myocardial injury and high burden of pre-existing cardiovascular disease is
significantly associated with higher mortality and ICU admission.

www.ncbi.nlm.nih.gov
 57

Hematologic manifestations:
Lymphopenia is a common laboratory abnormality in the vast majority of patients
with COVID-19.
Other laboratory abnormalities include thrombocytopenia, leukopenia, elevated ESR
levels, C- reactive protein (CRP) lactate dehydrogenase (LDH), and leukocytosis.
COVID-19 is also associated with a hypercoagulable state, evidenced by the high
prevalence of venous and thromboembolic events such as PE, DVT, MI, ischemic
strokes, and arterial thromboses.
COVID-19 is associated with markedly elevated D-dimer, fibrinogen levels, prolonged
prothrombin time (PT), and partial thromboplastin time(aPTT) in patients at risk of
developing arterial and venous thrombosis.

Gastrointestinal manifestations:
GI symptoms such as diarrhea, nausea and/or vomiting, anorexia, and
abdominal pain are seen in patients with COVID-19 infection
Cases of acute mesenteric ischemia and portal vein thrombosis have also
been reported.
Hepatobiliary manifestations:
Elevation in liver function tests manifesting as an acute increase in aspartate
transaminase(AST) and alanine transaminase(ALT) are frequently noted in
patients with COVID- 19 infection.
Hepatic dysfunction occurs more frequently in patients with severe COVID-19
illness.
Endocrinologic manifestations:
Patients with underlying endocrinologic disorders such as diabetes mellitus who
contract this virus are at increased risk of developing severe illness.
Clinical manifestations such as abnormal blood glucose levels, euglycemic
ketosis, and diabetic ketoacidosis have been noted in patients hospitalized with
COVID-19.
Neurologic manifestations:
Besides anosmia and ageusia, other neurological findings include headache, stroke,
impairment of consciousness, seizure disorder, and toxic metabolic
encephalopathy.
Five patients with COVID-19 developed Guillain-Barré syndrome (GBS) based on a
case series report from Northern Italy.
www.ncbi.nlm.nih.gov
 58

Cutaneous manifestations:
Acral lesions resembling pseudo chilblains were the most common cutaneous
manifestations noted in patients with COVID-19.
Other cutaneous manifestations described erythematous maculopapular rash,
vesicular rashes , and urticarial rashes.
Other uncommon rashes described were vascular rashes resembling livedo or
purpura, especially in elderly patients, and erythema multiforme-like eruptions,
mostly in children.

COVID in co morbid patients

ALC – Absolute lymphocyte count , NLR – Neutrophil lymphocyte ratio

[NLR –should be calculated prior to steroid administration]

www.icmr.gov.in
 59

Prevention of complications

www.icmr.gov.in
 60

Radiology
Chest X-ray
Standard radiographic examination (X-ray) of the chest has a low sensitivity in
identifying early lung changes; it can be completely normal in the initial stages of
the disease.
In the more advanced stages of infection, the chest X-ray examination commonly
shows bilateral multifocal alveolar opacities, which tend to confluence up to the
complete opacity of the lung. Pleural effusion can also be demonstrated.

(A) A 47-year-old woman with signs and symptoms raising suspicion of COVID-19.
Posteroanterior (PA) chest X-ray. Reticular interstitial pattern with peripheral predominance
(arrows).
(B) Same patient as in image A. PA chest X-ray taken 3 days later. Positive PCR for SARS-
CoV-2. Despite being taken with poorer inspiration, the X-ray shows faint rounded bilateral
peripheral alveolar opacities (dotted arrows).
(C) A 57-year-old male with dyspnoea and positive PCR for SARS-CoV-2. Bilateral peripheral
opacities in upper, middle and lower fields (arrow tips).
(D) A 45-year-old male with dyspnoea and COVID-19 confirmed by PCR. Anteroposterior chest
X-ray showing multiple bilateral diffuse confluent areas of consolidation with extensive
involvement of both lungs. Note the presence of two central venous lines, one left jugular and
the other right subclavian (white arrows), and a gastrointestinal tube (black arrow).
 61

Progressive bilateral ground-glass opacities

Bilateral ground-glass opacities more affecting both lungs, more prominent in the
prominent in the right upper lobe and right upper lobes and paramediastinal parenchyma.
paramediastinal region.

Chest Computed Tomography (CT)

The American College of Radiology recommends against Chest CT's routine use as an
initial imaging study or screening.
Given its high sensitivity, chest computed tomography (CT), particularly high-
resolution CT (HRCT), is the diagnostic method of choice in evaluating COVID-19
pneumonia, particularly when associated with disease progression.
The most common CT findings in COVID-19 are multifocal bilateral "ground or ground
glass" (GG) areas associated with consolidation areas with patchy distribution, mainly
peripheral/subpleural, and greater involvement of the posterior regions lower lobes.
The "crazy paving" pattern can also be observed.
This latter finding is characterized by GG areas with superimposed interlobular septal
thickening and intralobular septal thickening. It is a non-specific finding that can be
detected in different conditions.
Other notable findings include the "reversed halo sign," a focal area of GG delimited
by a peripheral ring with consolidation, and the findings of cavitations, calcifications,
lymphadenopathies, and pleural effusion.
 62
Typical findings in COVID-19 pneumonia on CT

Axial chest CT images with 1-mm slices.

(A) Ground-glass opacities with rounded morphology and a peripheral and
subpleural distribution (arrows).
(B) Consolidations with a peripheral and subpleural predominance (arrows).
(C) Reticulation with a peripheral and subpleural location (arrow tips).
(D) Peripheral ground-glass opacities with overlapping interlobular and intralobular
septal thickening in relation to a crazy-paving pattern (arrow). Peripheral
consolidation (asterisk) is also seen.

Reversed-halo sign: this represents a central ground-glass

opacity surrounded by a crescent- or ring-shaped consolidation.

Air-bubble (vacuolar) sign: this refers to a small hypodense

pulmonary space, less than 5 mm, within the ground-glass opacity.
 63

GGO – ground glass opacities

 64

CT SEVERITY INDEX (CTSI)

The severity of the lung involvement on the CT correlates with the severity of the
disease. CTSI is assessed by scoring the percentages of each of the five lobes that is
involved:
 65

0. No involvement 3. 26%-49% involvement

1. < 5% involvement 4. 50%-75% involvement
2. 5%-25% involvement 5. > 75% involvement.
The total CT score is the sum of the individual lobar scores and can range from 0 (no
involvement) to 25 (maximum involvement), when all the five lobes show more than
75% involvement.

Lung Ultrasound

Ultrasonographic examination of the lung allows evaluating the progression of the

disease, from a focal interstitial pattern up to a "white lung" with evidence of
subpleural consolidations.
Considering its noninvasive nature and zero risks of radiation, it is a useful
diagnostic modality for patient follow-up and assists in determining the setting of
mechanical ventilation and prone positioning.
The main sonographic features are:

Pleural lines: appear often thickened, irregular, and discontinuous until it

almost seems erratic; subpleural lesions can be seen as small patchy
consolidations or nodules.
B lines: They are often motionless, coalescent, and cascade and can flow up to
the square of "white lung."
Thickenings: They are most evident in the posterior and bilateral fields,
especially in the lower fields; the dynamic air bronchogram within the
consolidation is a manifestation of disease evolution.
Perilesional pleural effusion
 66

Pharmacology
 67

Treatment
• Patients categorized to A, B, C must be further risk stratified into mild, moderate and
severe.
• AVOID using NSAIDs other than paracetamol unless absolutely necessary.
• AVOID using nebulized drugs to avoid aerosolization of virus, use MDI instead.
• Oseltamivir should be initiated in all symptomatic patients with influenza like illness
till RTPCR/Antigen test result is obtained.
• In patients with COVID-19 pneumonia, secondary bacterial or viral infection is
uncommon. Initiation/continuation of antibiotics solely due to COVID-19 is not
indicated. Extended duration of fever is typical in COVID-19 patients. Based on
literature to date, no unique association between specific pathogens, such as MRSA or
Pseudomonas, has been made with COVID-19. Antibiotic selection in case of secondary
bacterial pneumonia should be as per institutional antibiogram.
• GINA and GOLD guidelines have recommended continuation of inhaled steroids even in
patients with COVID-19.
• Currently there are no data to support either starting or stopping ACEi /ARBs in any
patients with COVID-19. ACEi /ARB may be continued in patients who are already on
them. However, if acute kidney injury, hypotension or other contraindication develops,
consider stopping them at that time.
• If secondary pneumonia is not improving on broad spectrum antibiotics, consider the
possibility of CAPA [Covid Associated Pulmonary Aspergillosis] or pulmonary
mucormycosis.
68
 69

Favipiravir
Can lead to teratogenicity, transaminitis, neutropenia and dose dependent hyperuricemia.
Prior to using favipiravir or remdesivir, pregnancy has to be ruled out in all females in
reproductive age group. Favipiravir should not be used in pregnant and lactating females.
Favipiravir should be stopped if SGPT >5 times upper limit of normal or if creatinine
clearance is <30ml/min/m2 or if there is doubling of creatinine from baseline without an
alternative explanation.

REMDESIVIR
• Only in category C – moderate and severe disease
• No renal or hepatic dysfunction( egfr < 30ml/min/m2, AST/ALT > 5 times ULN)
– NOT an absolute contraindication
TOCILIZUMAB
Tocilizumab in combination with steroids is now recommended in patients with
1. Recently hospitalized patients who have been admitted to ICU within the prior 24 hours
and who require invasive mechanical ventilation, NIV or HFNC [ >0.4 FiO2/30L/min of
oxygen flow]
OR
2. Recently hospitalized patients with rapidly increasing oxygen needs who require NIV or
HFNC and have significantly increased markers of inflammation [CRP >75 mg/L was cut off
in RECOVERY trial]
 70

IVERMECTIN
• Pregnancy Category C – better to avoid
• Excreted in low concentration in human milk
• Metabolized in liver by Cytochrome p450 isoenzyme 3A4
• Azithromycin co administration may increase serum level of Ivermectin
• Concomittent alcohol use can increase severity of adverse effects

Tocilizumab is an anti-interleukin-6 receptor alpha

receptor monoclonal antibody

Sarilumab and Siltuximab are IL-6 receptor antagonists that

may potentially have a similar effect on the hyperinflammatory
state associated with COVID-19 as tocilizumab.
 71

Therapies In The Management Of Adults With COVID-19

Antiviral Therapies
Remdesivir
Broad-spectrum antiviral agent that previously demonstrated antiviral
activity against SARS-CoV- 2 in vitro.
There is no data available regarding the efficacy of remdesivir against the new
SARS-CoV-2 variants; however, acquired resistance against mutant viruses is
a potential concern and should be monitored.
Hydroxychloroquine and chloroquine
Antiviral treatments for COVID-19 initially during the pandemic.
However, data from randomized control trials evaluating the use of
hydroxychloroquine with or without azithromycin in hospitalized patients did not
improve the clinical status or overall mortality compared to placebo.
Lopinavir/ritonavir
FDA-approved combo therapy for the treatment of HIV and was proposed as
antiviral therapy against COVID-19 during the early onset of the pandemic.
Lopinavir/Ritonavir is currently not indicated for the treatment of
COVID-19 in hospitalized and nonhospitalized patients.
Ivermectin
FDA-approved anti-parasitic drug used worldwide in the treatment of COVID-19
based on an in vitro study that showed inhibition of SARS-CoV-2 replication.
Ivermectin is currently not indicated for the treatment of COVID-19 in
hospitalized and nonhospitalized patients.

Anti-SARS-CoV-2 Neutralizing Antibody Products

Individuals recovering from COVID-19 develop neutralizing antibodies against
SARS-CoV-2, and the duration of how long this immunity lasts is unclear.
Nevertheless, their role as therapeutic agents in the management of COVID-19
is extensively being pursued in ongoing clinical trials.
Convalescent Plasma therapy
Cocktail 1 and 2

www.ncbi.nlm.nih.gov
 72

Convalescent Plasma therapy

The FDA approved convalescent plasma therapy under a EUA for patients with
severe life-threatening COVID-19.
 73

REGN-COV2 (Casirivimab and Imdevimab)

REGN-COV2 is an antibody cocktail containing two noncompeting IgG1 antibodies
(casirivimab and imdevimab) that target the RBD on the SARS-CoV-2 spike
protein that has been shown to decrease the viral load in vivo, preventing virus-
induced pathological sequelae when administered prophylactically or
therapeutically in non-human primates.
Bamlanivimab and Etesevimab
(LY-CoV555 or LY3819253 and LY-CoV016 or LY3832479)
Potent anti- spike neutralizing monoclonal antibodies.
Bamlanivimab is a neutralizing monoclonal antibody derived from convalescent
plasma obtained from a patient with COVID-19. Like REGN-COV2, it also targets the
RBD of the spike protein of SARS-CoV-2 and has been shown to neutralize SARS-
CoV-2 and reduce viral replication in non- human primates.

REGN-COV2 (casirivimab and imdevimab) and bamlanivimab/etesevimab were

approved for clinical use by the FDA under two separate EUAs that allowed the use of
these drugs only in nonhospitalized patients (aged ≥12 years and weighing ≥40 kg)
with laboratory-confirmed SARS-CoV-2 infection and mild to moderate COVID-19 who
are at high risk for progressing to severe disease and/or hospitalization.

www.ncbi.nlm.nih.gov
 74

casirivimab and imdevimab

Developed by: Roche
Approved by: central drugs standard control organisation (CDSCO)
History of use:
i) Former U..S President Donald Trump had taken the drug when contracted
COVID-19.
ii) Used in emergency treatment of mild moderate COVID-19 in high risk
patients
Nature of Drug: Monoclonal antibodies- mimic immune systems ability to fight
off the virus
Mechanism of action
 75

Cocktail 1 Cocktail 2

Bamlanivimab and Etesevimab Casirivimab and Imdevimab

Attaches on the. Same ‘S’ protein Attaches on the different‘S’ protein

Approved by US FDA Approved by US FDA
Helped to treat B.1.1.7 mutation Helped to treat B.1.351 and B.1.617
that caused 2nd wave in US mutation that caused 2nd wave in
Not approved by CDSCO INDIA India
Approved by CDSCO INDIA

Route of administration
IV administration
Single dose
Used
Within 10 days of onset of symptoms
Not used
Hospitalised Covid-19
Who require O2 therapy
Side effects
Serious hypersensitivity reaction
Vaccination
Delayed > 90days after cocktail MAB treatment since it can induce vaccine
induced immune response

Dosage
700mg

i
Bamlanivimab
+ Cocktail 1
Etesevimab 1400mg

Casirivimab 1200mg
+ Cocktail 2
Imdevimab 1200mg
 76

Immunomodulatory Agents
Corticosteroids:
Severe COVID-19 is associated with inflammation-related lung injury driven
by the release of cytokines characterized by an elevation in inflammatory
markers.
Dexamethasone is currently considered the standard of care either alone or in
combination with remdesivir based on the severity of illness in hospitalized
patients who require supplemental oxygen or non-invasive or invasive
mechanical ventilation.

Interferon-β-1a (IFN- β-1a)

Interferons are cytokines that are essential in mounting an immune response
to a viral infection, and SARS-CoV-2 suppresses its release in vitro.
Currently, there is no data available regarding the efficacy of interferon β-1a on
the three new SARS-CoV-2 variants (B.1.1.7; B.1.351 and P.1). Given the insufficient
and small amount of data regarding this agent’s use and the relative potential for
toxicity, this therapy is not recommended to treat COVID-19 infection.
Interleukin (IL)-1 Antagonists
Anakinra is an interleukin-1 receptor antagonist that is FDA approved to
treat rheumatoid arthritis.
There is no data available regarding the efficacy of interleukin-1 receptor
antagonists on the three new SARS-CoV-2 variants (B.1.1.7; B.1.351, and
P.1). Given the insufficient data regarding this treatment based on case
series only, this is not currently recommended to treat COVID-19 infection.
Anti-IL-6 receptor Monoclonal Antibodies:
Interleukin-6 (IL-6) is a proinflammatory cytokine that is considered the key
driver of the hyperinflammatory state associated with COVID-19.
Targeting this cytokine with an IL-6 receptor inhibitor could slow down the process
of inflammation based on case reports that showed favorable outcomes in patients
with severe COVID-19.
The FDA approved three different types of IL-6 receptor inhibitors for various
rheumatological conditions (Tocilizumab, Sarilumab) and a rare disorder called
Castleman’s syndrome (Siltuximab).

www.ncbi.nlm.nih.gov
 77

Janus kinase (JAK) inhibitors

Baricitinib is an oral selective inhibitor of Janus kinase (JAK) 1 and JAK 2
currently indicated for moderate to severely active rheumatoid arthritis
patients.
Baricitinib was considered a potential treatment for COVID-19 based on
its inhibitory effect on SARS-CoV-2 endocytosis in vitro and on the
intracellular signaling pathway of cytokines that cause the late-onset
hyperinflammatory state that results in severe illness.
This dual inhibitory effect makes it a promising therapeutic drug against
all stages of COVID-19.

Ruxolitinib is another oral selective inhibitor of JAK 1 and 2 that is indicated for
myeloproliferative disorders, polycythemia vera, and steroid-resistant GVHD.
Similar to baricitinib, it has been hypothesized to have an inhibitory effect on
cytokines’ intracellular signaling pathway, making it a potential treatment
against COVID-19.
Bruton’s tyrosine kinase inhibitors
Acalabrutinib, ibrutinib, rilzabrutinib are tyrosine kinase inhibitors that
regulate macrophage signaling and activation currently FDA approved for
some hematologic malignancies.
It is proposed that macrophage activation occurs during the
hyperinflammatory immune response seen in severe COVID-19.

2-DG (2- Deoxy D- Glucose)

2-DG (2- Deoxy D- Glucose) is found to be effective in treatment of COVID-19.
Glucose provides energy in the form of ATP to viral host cells via Glycolysis.
It also enables the creation of Glycan supporting the creation of Glycoprotein
during Glycosylation.
These glycoprotein enable host attachment, uptake and reinfection (replication)
Oral drug in powdered sachets
Approved by: Drug controller general of India- DCGI
Developed by: Defence emergency research and development organisation
DRDO and Dr. Reddy’s Laboratory

www.ncbi.nlm.nih.gov
 78

The D-Glucose stay as the main ingredient

for both Glycosylation and glycolysis.

2-DG look like glucose , it is known as Glucose Decoy.

It has one of the OH group seen in natural glucose removed.
2-DG will not convert into energy via glycolysis and it will not form the
proper building blocks for glycan formation during Glycosylation.
This property of 2-DG is used for the treatment of moderate and severe
Covid infection.

Effects in treatment with 2-DG.

Symptoms improved by 3rd day
Decrease oxygen requirement
 79
Role of glycoprotein
 80

nutritional management in COVID patients

 81

Anticoagulation algorithm in COVID -19

 82

Covid-19 vaccine
Vaccination triggers the immune system leading to the production of neutralizing
antibodies against SARS-CoV-2.

Immunogens used in current COVID-19 vaccines or COVID-19 vaccines in development:

Inactivated virus
Viral subunit
Viral vector
RNA vaccines
 83

Inactivated virus vaccine

• In inactivated virus vaccines, the
genetic material of the virus has
been destroyed to stop disease
producing capacity
• Inactivated virus cannot replicate
inside the body, so higher doses are
needed
• Sometimes, an adjuvant
(molecules that stimulate the
immune system) is used to help
strengthen the immune response
• Inactivated virus vaccines
generally only induce antibody-
mediated immunity (not cell-
mediated immunity)

Viral subunit vaccines

• Subunit vaccines use the antigen of
the virus without any genetic
material, usually with an adjuvant to
give a better immune response
• Usually made using recombinant
expression system (made in a cell
without using the virus)
• With the help of antigen-presenting
cells, the antigens are recognised by T
helper cells as with a real viral
infection
• Subunit vaccines generally induce
mainly antibody-mediated immunity
• Adjuvants can enhance antibody
response and also cell-mediated
immunity
 84

Viral vector vaccines

• Viral vector vaccines use a non-
coronavirus vector modified to
include a gene that encodes a target
antigen
• Can be replicating or non-
replicating.
• Non-replicating: infects a cell and
produces SARS-CoV-2 antigen in
that cell but not new virus.
• Replicating: upon infection
produces SARS-CoV-2 antigen in
that cell and new virus which infects
other cells.
• The SARS-CoV-2 antigen inside
cells seen by body as if SARS-CoV-2
infection and induces T helper cells
and cytotoxic T cells.
RNA vaccine
• RNA vaccines are antigen-coding
strands of messenger RNA (mRNA)
delivered inside a lipid coat
• Once inside cells, the mRNA is
translated the protein antigen
• The antigen is recognised, inducing
an immune reaction
• Seen by body as if virus inside cell
so induces T-helper and cytotoxic T-
cells, and antibodies.
• mRNA also recognised by cells as
‘pathogen’ stimulating strong
immune response.
 85

Covishield vaccine

i. Developer : Serum Institute of India

ii. Viral vector based recombinant vaccine : ChAdOx1 nCoV-19
Same as COVID-19 vaccine AstraZeneca used in Europe and USA
iii. Type of vaccine : AZD1222
Monovalent vaccine, single recombinant, replication deficient chimpanzee
adenovirus (ChAdOx1) vector encoding S glycoprotein of SARS-CoV-2
iv. Produced by genetically modified HEK293 cells (Human embryonic kidney).
v. MOA : Local expression of S glycoprotein of SARS-CoV-2
Leads to neutralising antibody and cellular immune response
vi. Age groups : 18 years and above

Dose, route 0.5 ml each- 2 doses 8-12 weeks apart, intramuscular

Site deltoid
Storage +2- +8°C

Adverse Headache, nausea, myalgia, arthralgia,

reactions injection site reactions -very common
Vomiting, injection site induration, influenza
like illness -common

Contraindication hypersensitivity
hypersensitivity, concurrent illness,
Precaution thrombocytopenia/ coagulation disorders,
immunocompromised

Protective 70.42 %
efficacy
 86

Covaxin vaccine

i. Developer : Bharat Biotech, ICMR and National Institute of Virology

ii. Indigenous vaccine
iii. Type of vaccine : Whole virion inactivated SARS-CoV-2 vaccine : BB152
iv. Strain : NIV-2020-770
v. Strength : 6 mcg per 0.5 ml dose
vi. Age group : 18 years and above

Dose, route 0.5 ml each- 2 doses 4 weeks apart, intramuscular only

Site deltoid
Storage +2 - +8°C
injection site pain, fatigue, fever, body-ache,
Adverse abdominal pain, nausea, vomiting - common
reactions Tremor, cough, cold, sweating, injection site
swelling, dizziness - less common
hypersensitivity, fever/ severe
infection age < 18 years
Contraindication
Interactions -chloroquine,
corticosteroids

Sero-conversion 86~96%
rate
 87

Pfizer-BioNTech vaccine

i. BNT162b2
ii. Generic name : Tozinameran
iii. Brand name : Comirnaty
iv. Type : nucleoside modified mRNA which encodes
part of the spike protein found on the surface of
the SARS-CoV-2 coronavirus, triggering an
immune response against infection by the virus
protein
v. MOA : mRNA that carries instructions for
making the virus’s spike protein
Recognised as foreign by the immune system so
antibodies, B cells and T cells are activated
vi. Age group : 16 years above

Dose, route 0.3 ml each- 2 doses 3 weeks apart, intramuscular

Site deltoid

Diluent 0.9 % NaCl for reconstitution

Storage -80 ~ -60°C frozen form till ready to use

Thawing +2 ~ +8°c or room temperature upto 25°c
After dilution keep within +2 ~ +8°c (use within
6 hours) (do not refreeze)
injection site pain, tiredness, headache,
Adverse muscle pain, chills, joint pain, fever, injection
reactions site swelling/ redness, nausea,
lymphadenopathy

Contraindication Severe allergic reaction

efficacy 95 %
 88

Moderna vaccine

i. mRNA-1273 vaccine
ii. Manufactured by Moderna, NIAID and BARDA
iii. Type of vaccine : nucleoside modified messenger RNA compound
mRNA-1273 encode prefusion stabilised spike protein naturally
present on the surface of SARS-CoV-2 particles
iv. Drug delivery system : PEGylated lipid nanoparticle (LNP)
v. MOA : mRNA that carries instructions for making the virus’s
spike protein
Recognised as foreign by the immune system so antibodies,
B cells and T cells are activated
vi. Age group : 18 years and above

Dose, route 0.5 ml each- 2 doses 4 weeks apart, intramuscular

Site deltoid
+2- +8°C
Storage
-40°C Upto 4 months

Adverse Facial swelling, bell’s palsy

reactions Pain at the injection site, tiredness, headache,
muscle pain, chills, joint pain, lymphadenopathy,
nausea, vomiting, fever -common

Contraindication Severe allergic reaction

Protective 94.5 %
efficacy
 89

Anaesthesia

Conventional Oxygen Therapy

COVID-19 patients with associated respiratory insufficiency should be monitored
closely with continuous pulse oximetry.
Supplemental oxygen supplementation via nasal cannula or Venturi mask must be
administered to maintain oxygen saturation (SpO2) between 92 to 96% (< 88-90% if
COPD).
If there is improvement in clinical and oxygen saturation, supplemental oxygen
should be continued with periodic reassessment.
If there is no clinical improvement or worsening of symptoms and/or oxygen
saturation, non-invasive treatments such as High-Flow Nasal Cannula (HFNC) or
Noninvasive Positive Pressure Ventilation(NIPPV) are recommended.

Noninvasive Positive-pressure Ventilation (NIPPV)

NIPPV (bilevel positive airway pressure [BiPAP]/continuous positive airway pressure
[CPAP]) is instrumental in the management of COVID-19-associated acute
hypoxemic respiratory failure and may help avoid invasive mechanical ventilation in
carefully selected patients.
NIPPV should be restricted to hospitalized patients with COVID-19 who develop
respiratory insufficiency due to COPD, cardiogenic pulmonary edema, or have
underlying obstructive sleep apnea (OSA) rather than ARDS.
A helmet is preferred for minimizing the risk of aerosolization. In NIPPV with face
masks (full-face or oronasal), the use of masks integrated with an expiratory valve
fitted with an antimicrobial filter is recommended.
Results from the HENIVOT trial, an Italian open-label multicenter randomized
clinical trial, reported that there was no significant difference in the number of days
free of respiratory support with the utilization of helmet noninvasive ventilation
treatment compared to high flow nasal oxygen in COVID-19 patients hospitalized
with moderate to severe degree of hypoxemia.
 90

High-Flow Nasal Cannula (HFNC) and Noninvasive Positive Pressure Ventilation

(NIPPV)are noninvasive enhanced respiratory support modalities available in
managing COVID-19- associated acute hypoxemic respiratory failure and are
instrumental in avoiding invasive mechanical ventilation in carefully selected patients.
These treatment modalities are associated with a greater risk of aerosolization and
should be used in negative pressure rooms.

Endotracheal Intubation and Lung Protective

Invasive Mechanical Ventilation
Impending respiratory failure should be recognized as early as possible, and a skilled
operator must promptly perform endotracheal intubation to maximize first-pass
success.
Clinicians and other healthcare staff must wear appropriate PPE that includes gowns,
gloves, N95 masks, and eye protection when performing endotracheal intubation and
manual ventilation before intubation, physical proning of the patient, or providing
critical patient care such as upper airway suctioning, disconnecting the patient from
the ventilator.
Preoxygenation (100% O2 for 5 minutes) should be performed via HFNC.
Invasive mechanical ventilation in COVID-19 associated acute hypoxemic respiratory
failure and ARDS should be with lower tidal volumes (V.T.) (4 to 8 ml/kg predicted
body weight, PBW) and lower inspiratory pressures reaching a plateau pressure
(Pplat) < 30 cm of H2O.
Positive end-expiratory pressure (PEEP) must be as high as possible to maintain the
driving pressure (Pplat-PEEP) as low as possible (< 14 cmH2O).
Use of neuromuscular blocking agents (NMBA) should be used as needed to facilitate
lung-protective ventilation.
In patients with refractory hypoxemia (PaO2:FiO2 of <150 mm Hg), prone ventilation
for > 12 to 16 hours per day and the use of a conservative fluid management strategy
for ARDS patients without tissue hypoperfusion are strongly emphasized.
The National Institutes of Health (NIH) Covid-19 Treatment Guidelines Panel
recommends against inhaled pulmonary vasodilators such as nitric oxide.
Lung-protective ventilation can also reduce the risk of new or worsening AKI by
preventing ventilator-induced hemodynamic effects.
ECMO should be considered in carefully selected patients with refractory hypoxemia
despite lung-protective ventilation and patients who fail to respond to prone position
ventilation.
91
 92

Aerosol generating procedures include:

o Intubation
o Extubation
o Bronchoscopy
o High flow nasal oxygen use
o Non-invasive ventilation (particularly with a poorly fitting mask)
o Procedures on screaming children
o Tracheostomy
o CPR prior to intubation

Infection control
Although regional anesthesia is considered to have a lower risk of COVID-19
transmission than general anesthesia, safety protocols should be followed to prevent
infection from droplets and contaminated sources.
Personal protective equipment includes a surgical mask, eye protection, surgical
gown, and double glove.
The use of N95 masks should be considered depending on the risk of aerosol
generation and droplet spread.
Restrictions of staff and equipment in the operating room should be considered to
minimize exposure to the virus.

Cardiac Arrest:
AHA 2020 with modification to limit transmission
❖ Avoid mouth to mouth or pocket mask ventilation
❖ The staff should have gown, gloves, eyeshield or goggles before starting CPR
(complete aerosol generating procedure PPE).
❖ Start CPR with chest compression.
❖ If patient is having oxygen mask before start of CPR leave it in situ to limit spread
of aerosol.Otherwise if readily available put a mask and start CPR. Limit entry of
people into the room during CPR.
❖ For bag and mask ventilation, connect HME or bacterial filter to it to limit aerosol
generation. Use 2-person technique for bagging, one person to hold the face mask
tight with E-V technique while the other ventilates to minimise aerosol generation.
❖ Identify and treat any reversible causes.
❖ Defibrillate shockable rhythms rapidly
 93

Surgery
Surgical patients may be classified into three risk categories for COVID-19: confirmed
and suspected patients, high-risk patients, and low-risk patients.
They are defined as follows:
1 Confirmed and suspected patients: COVID-19 was confirmed when real-time
reverse transcriptase (RT)-PCR diagnostic panels or serological (IgM and IgG)
test results was positive. The definition of suspected cases falls into two
categories. The first category will have contact history and meet any two of the
clinical manifestations (fever and respiratory symptoms) with the typical
findings of COVID-19 in the chest CT scan. The total number of white blood cells
in the early stage of the disease is normal or decreased, and the lymphocyte
count is reduced. The second category is without a clear epidemiological history
and shows three of the clinical manifestations (fever and/or respiratory
symptoms, with the typical findings in the chest CT. The blood count will be as
described above .
2 High-risk patients: Patients who had traveled to high-risk areas or contacted
patients with confirmed or suspected COVID-19 (who have developed fever and/
or symptoms of acute respiratory illness within 14 days).
3 Low-risk patients: Patients with no history of close contact with confirmed and
suspected COVID-19 patients and with no fever or respiratory symptoms and
without CT manifestations of COVID-19 within 14 days.

Prevention Measures for Healthcare Workers

1 When entering the ward of low-risk or high-risk patients for daily activities and
rounds, primary protection (disposable surgical cap, surgical mask, work uniform and
disposable latex gloves or/and disposable isolation clothing if necessary) is needed.
2 When carrying out routine activities and rounds with confirmed and suspected patient
wards, secondary protection (disposable surgical cap, N95 mask, work uniform,
disposable medical protective uniform, disposable latex gloves and goggles) should be
used.
3 For special procedures such as collecting airway samples, tracheal intubation, airway
care, and sputum suction, tertiary protection measures (disposable surgical cap, N95
mask, work uniform, disposable medical protective uniform, disposable latex gloves,
full-face respiratory protective devices or powered air-purifying respirator) should
be implemented as aerosol or spray may occur in airborne infection isolation rooms.
 94
Protocols for Emergency Surgery
1 For confirmed and suspected patients, surgeons need to report to the hospital’s
epidemic management department (if any), infection control department, and
operating theater before surgery and then transfer to a negative pressure
operating theater via a path. Tertiary protection measures are needed for
anesthesia and surgical procedures. After the operation, patients are
transferred to the isolation area.
2 For high-risk patients, after the preoperative preparation is completed, the
anesthesiologist, nurse, and surgeon should follow tertiary protection measures
for anesthesia and surgical procedures. After the operation, the patients are
returned to the original isolation ward according to the original transfer route.
3 For low-risk patients, the general protection measures are needed for
anesthesia and surgical procedures. After the operation, patients are
transferred to the original ward according to the original transfer route.

Protocols for Elective Surgery

1 If the patient’s RT PCR test is twice negative, according to the patient’s current
epidemic level, surgeons can proceed with surgical protocols.
2 If the patient’s RT PCR test is positive, then the patient needs to be transferred
to the isolation ward to complete the preoperative preparation. Elective surgery
should be deferred until the patient recovers. If we have to operate emergently
on such patients for any reasons, all the precautions mentioned earlier for
operating COVID-19-positive cases as emergency should be strictly followed.
The tertiary protection measures should be taken during the anesthesia and
operation. After the operation, patients are returned to the isolation area.

Postoperative Management
In the operating theater, laminar air flow is used, and air supply should be closed
after operation.
Peroxyacetic acid air is used for fumigation.The operating theater should be
cleaned and disinfected and high-efficiency filter changed.
Cleansing should be done using detergent and water followed by use of with
1000 ppm bleach solution for all hard surfaces in the operating theater. The
disinfection time should be longer than 30 min.
The operating theater should be closed for at least 2 h, and the next operation
should be performed after laminar flow and ventilation being turned on
 95

ENT
Mucormycosis

Mucormycosis is a fungal infection that mainly affects people who are on

medication for other health problems that reduces their ability to fight
environmental pathogens.
Sinuses or lungs of such individuals get affected after fungal spores are
inhaled from the air.
Time of presentation: variable but usually around 3rd week of onset of
symptoms of Covid – 19.
warning sign and symptoms
1. Facial pain, pain over sinuses, pain in teeth and gums
2. Paraesthesia / decreased sensation over half of face.
3. Blackish discolouration of skin over nasolabial groove/ alae nasii.
4. Nasal crusting and nasal discharge which could be blackish or blood
tinged.
5. Conjunctival injection or chemosis.
6. Periorbital swelling.
7. Blurring of vision/ diplopia.
8. Loosening of teeth/ discoloration of palate/ gangrenous inferior
turbinates.
9. Worsening of respiratory symptoms, hemoptysis, chest pain, alteration
of consciousness, headache.

Predisposing factors
1. Hyperglycemia due to uncontrolled pre-existing diabetes and high prevalence
rates of mucormycosis in India per se.
2. Rampant overuse and irrational use of steroids in management of Covid – 19.
3. New onset diabetes due to steroid overuse or severe cases of Covid – 19 per se.
4. Prolonged ICU stay and irrational use of broad spectrum antibiotics
5. Pre-existing co-morbidities such as hematological malignancies, use of
immunosuppressants, solid organ transplant etc.
6. Breakthrough infections in patients on Voriconazole (anti – fungal drug)
prophylaxis.
 96

How to prevent
Use masks if you are visiting dusty construction sites
Wear shoes, long trousers, long sleeve shirts and gloves while
handling soil (gardening), moss or manure
Maintain personal hygiene including thorough scrub bath

Treatment
Control diabetes and diabetic ketoacidosis
Reduce steroids (if patient is still on) with aim to discontinue rapidly
Discontinue immunomodulating drugs
No antifungal prophylaxis needed
Extensive Surgical Debridement - to remove all necrotic materials
Medical treatment
Install peripherally inserted central catheter (PICC line)
Maintain adequate systemic hydration
Infuse Normal saline IV before Amphotericin B infusion
Antifungal Therapy, for at least 4-6 weeks (see the
guidelines below )
Monitor patients clinically and with radio-imaging for response and to detect
disease progression

Dos
Control hyperglycemia
Monitor blood glucose level post COVID-19 discharge and also in diabetics
Use steroid judiciously – correct timing, correct dose and duration
Use clean, sterile water for humidifiers during oxygen therapy
Use antibiotics/antifungals judiciously
Don’ts
Do not miss warning signs and symptoms
Do not consider all the cases with blocked nose as cases of bacterial sinusitis,
particularly in the context of immunosuppression and/or COVID-19 patients on
immunomodulators
Do not hesitate to seek aggressive investigations, as appropriate (KOH staining &
microscopy, culture, MALDI- TOF), for detecting fungal etiology
Do not lose crucial time to initiate treatment for mucormycosis
 97

Rhinocerebral (sinus and • One-sided facial swelling

brain) mucormycosis • Headache
• Nasal or sinus congestion
• Black lesions on nasal bridge or upper inside of
mouth that quickly become more severe
• Fever
• Lethargy, seizures, slurred speech, partial
paralysis
Pulmonary (lung) • Fever
mucormycosis • Cough
• Chest pain
• Shortness of breath
• Hemoptysis

Cutaneous (skin) Skin lesion that resembles blisters or ulcers. The

mucormycosis infected area may turn black. Other symptoms
include pain, warmth, excessive redness, or
swelling around a wound.

Gastrointestinal • Abdominal pain

mucormycosis • Nausea and vomiting
• Gastrointestinal bleeding

Disseminated Tends to occur in people who are already sick from

mucormycosis other medical conditions, which makes it difficult to
identify which symptoms are related to
mucormycosis. Patients with disseminated
infection in the brain may develop mental status
changes or coma.
 98

Investigation
i. NCCT PNS ( to see bony erosion).
ii. HRCT chest ( ≥ 10 nodules, reverse halo sign, CT bronchus sign etc.)
and CT Angiography.
iii. MRI brain for better delineation of CNS involvement.

Diagnosis
i. KOH staining and microscopy, histopathology of debrided tissue and culture
ii. MALDI-TOF if available
iii. Presence of Ribbon like aseptate hyphae 5-15 µ that branch at right angles.

Management

One should have a high index of suspicion of invasive fungal infection such as
Mucormycosis in the presence of predisposing conditions as mentioned above.
Timely initiation of treatment reduces mortality. Multidisciplinary Team
approach is required. Treatment of Mucormycosis involves combination of
surgical debridement and antifungal therapy.
Liposomal Amphotericin B in initial dose of 5mg/kg body weight (10 mg/kg body
wt in case of CNS involvement) is the treatment of choice. Each vial contains 50
mg. It should be diluted in 5% or 10% dextrose, it is incompatible with normal
saline/ Ringer Lactate.. It has to be continued till a favourable response is
achieved and disease is stabilized which may take several weeks following which
step down to oral Posaconazole (300 mg delayed release tablets twice a day for 1
day followed by 300 mg daily) or Isavuconazole (200 mg 1 tablet 3 times daily for
2 days followed by 200 mg daily) can be done.
The therapy has to be continued until clinical resolution of signs and symptoms
of infection as well as resolution of radiological signs of active disease and
elimination of predisposing risk factors such as hyperglycemia,
immunosuppression etc, it may have to be given for quite long periods of time.
Conventional Amphotericin B (deoxy cholate) in the dose 1-1.5mg/kg may be
used if liposomal form is not available and renal functions and serum
electrolytes are within normal limits.
99
 100

Management of ROCM
 101

Ophthalmology
Ophthalmologists are at a high-risk due to the following three important reasons:
Presence of virus in the tear fluid,
Proximity of encounter and
Deceiving symptoms.

Ophthalmological signs and symptoms of coronavirus disease

COVID-19 in ophthalmologic patient care

1 Minimize ambient noise so people do not need to speak loudly: turn off televisions/
music; use fans which generate minimal noise.
2 Restrooms: require people to wait several minutes after someone leaves the
restroom before going in (to allow time for droplets to settle). Bathroom surfaces
should be considered contaminated unless no one has used the restroom since it was
disinfected. Consider restroom signage and possible monitoring.
3 Any environment that is enclosed, with poor air circulation and high density of
people, spells trouble. Being in an enclosed space, sharing the same air for a
prolonged period, increases the chances of exposure and infection. Limit small
enclosed work spaces to one employee. Move diagnostic equipment currently in small
rooms/alcoves to larger work spaces.
4 Airflow -- people downwind of others are at higher risk: map airflow patterns to
identify higher risk areas and curtail use of those areas as feasible; maximize
ventilation -- open doors; open windows; maximize fan intensity/air flow with central
air systems; use single pass (outside air) rather than recycled air in central air
systems; increase ventilation of elevators if this is feasible.
 102

5 Fomite transfer (in addition to medical equipment) is in need of attention:

countertops, cell phones, ID's, door handles, pens, clipboards, tissue dispensers,
water coolers, elevator buttons etc.
6 Social distancing guidelines don't hold in indoor spaces (with limited air
exchange or recycled air and lots of people) where you spend a lot of time, as
people on the opposite side of the room from a COVID-19 spreader can get
infected. Social distancing rules are really to protect you with brief exposures.

Contact lens practice

A contact lens specialist should keep away from touching his/her
face and mucus membrane-covered areas such as nose, mouth and
eyes.
CLs should be adequately cleaned, and disposable CLs should not be
used longer than what is recommended.
Individuals should be told to discontinue CL wear if they have any
symptoms of COVID-19
Prevention in Healthcare workers

A summary of potential strategies in hygiene practices, personal protective equipment and non-
pharmacological interventions for the prevention of infection among the ophthalmologists and patients
visiting ophthalmology clinics.
 103

Obstetrics
Pregnancy and COVID-19

Antenatal care
Women should be advised to attend routine antenatal care, tailored to minimum,
at the discretion of the maternal care provider at 12, 20, 28 and 36 weeks of
gestation, unless they meet current self-isolation criteria.
For women who have had symptoms, appointments can be deferred until 7 days
after the start of symptoms, unless symptoms (aside from persistent cough)
become severe. Foetal Kick count to be maintained.
If needed to visit health centre, should take own transport or call 108, informing
the ambulance staff about her status.
For women who are self-quarantined because someone in their household has
possible symptoms of COVID-19, appointments should be deferred for 14 days.
Any woman who has a routine appointment delayed for more than 3 weeks should
be contacted.
Even if a woman has previously tested negative for COVID-19, if she presents with
symptoms again, COVID-19 should be suspected.
Referral to antenatal ultrasound services for foetal growth surveillance is
recommended after 14 days following the resolution of acute illness.
 104
Care in labor
Aim to keep oxygen saturation >94%, titrating oxygen therapy accordingly.
If the woman has signs of sepsis, investigate and treat as per guidance on sepsis in
pregnancy, but also consider active COVID-19 as a cause of sepsis and investigate
according to guidance.
Continuous electronic foetal monitoring in labour is recommended.
There is no evidence that epidural or spinal analgesia or anaesthesia is
contraindicated in the presence of coronaviruses. Epidural analgesia should therefore
be recommended in labour to women with suspected/confirmed COVID- 19 to minimise
the need for general anaesthesia if urgent delivery is needed.
In case of deterioration in the woman’s symptoms, make an individual assessment
regarding the risks and benefits of continuing the labour, versus emergency
caesarean birth if this is likely to assist efforts to resuscitate the mother.
When caesarean birth or other operative procedure is advised, it should be done after
wearing PPE.
An individualised decision should be made regarding shortening the length of the
second stage of labour with elective instrumental birth in a symptomatic woman who
is becoming exhausted or hypoxic.
Postnatal care
Facilities should consider temporarily separating (e.g. separate rooms) the mother
who has confirmed COVID-19 or is a PUI, from her baby until the mother’s
transmission-based precautions are discontinued.
The risks and benefits of temporary separation of the mother from her baby should
be discussed with the mother by the healthcare team.
The decision to discontinue temporary separation of the mother from her baby should
be made on disease severity, laboratory results.
If Rooming in, Consider using engineering controls like physical barriers and keeping
the new-born ≥6 feet away from the ill mother.
Breastfeeding
During temporary separation, mothers who intend to breastfeed should be
encouraged to express their breast milk to establish and maintain milk supply.
Prior to expressing breast milk, mothers should practice hand hygiene.
This expressed breast milk should be fed to the new-born by a healthy caregiver.
If a mother and new-born do room-in and the mother wishes to feed at the breast,
she should put on a facemask and practice hand hygiene before each feeding.
 105

COVID 19 is NOT an indication for c -section

 106

COVID 19 treatment considerations in pregnancy

D Dimer cut offs in normal pregnancy

First Trimester 169-1202 mcg/L

Second trimester 393-3258mcg/L

Third trimester 551-3333mcg/L

 107
Medical management
Supportive therapy include rest, oxygen supplementation,
Fluid management & nutritional care
Hydroxychloroquine in a dose of 600 mg (200 mg thrice a day with meals) and
Azithromycin (500 mg once a day) for 10 days
Anti-viral therapy: Lopinavir-ritonavir,Remdesivir,Oseltamavir
Antibiotics: If there is a suspicion of secondary bacterial infection
Oxygen: If there is diffculty in breathing,
oxygen supplementation by nasal prongs or mass
Indications for ICU Admission
Respiratory rate > 30 breaths/min
Oxygen saturation < 93% at a rest
PaO2/FiO2 < 300 mm Hg
Patients with > 50% lesions progression within 24 to 48 hours in lung imaging
qSOFA score can be a useful adjunct to decision making for ICU management

Discharge home with return precautions

Mild/ Moderate No risk Factors for Supportive therapy
No pneumonia decompensation Rest and Plenty of fluids
Mild pneumonia
Normal vital signs
Risk factor Admission
COVID 19 in DM/HTN Fluid management
Severe/ Critical Hydroxychloroquine and Azithromycin
pregnancy Age>40
Hypoxia Third trimester Anti-viral therapy
Tachypnea Antibiotics: secondary bacterial infection
Dyspnea Oxygen supplementation
> 50% lung infiltrates Admit to
Respiratory failure tertiary care
Shock center

Q. A 30 yrs old G3P2 at 34 wks of gestation presented to the opd with complaints of
breathlessness and cough. The patient’s husband was diagnosed with COVID one week
back and is currently at home isolation. She has been diagnosed with GDM and is
currently on dietary restrictions. Oxygen saturation is 94%. The lungs are clear to
auscultation bilaterally. Cardiac examination demonstrates normal heart sounds.
The abdomen is nontender, and the uterine fundus measures 34 weeks gestation. RT
PCR test for COVID was done which was positive and she was admitted in a first line
Covid treatment facility. What is the next line of management?
 108

Paediatrics
Common symptoms
•
Fever •
Anorexia/nausea/vomiting
Sore throat/throat irritation • Rhinorrhoea

,•⑧
Diarrhoea
Cough
•

•
Malaise/weakness
Loss of sense of smell and/or taste
•
Body ache/headache
Care of neonates born to COVID-19 positive mothers
•
Majority of these neonates remain asymptomatic.
•
Occasionally, moderate to severe infections with oxygen requirement can occur.
•
A significant proportion of neonates may however require special or intensive care due to
prematurity and perinatal complications.
•Breastfeeding, rooming-in, kangaroo mother care (when required) should be encouraged
in all cases.
•
Therefore, the pediatric facility should have equipment and surgical consumables suitable
for neonates including preterms.
•
Routine immunization should be done for stable neonates.
Classification based on symptoms and signs
Differentiating Asymptomatic Mild Moderate Severe
symptoms/signs
Respiratory Normal Normal Rapid respiration Rapid respiration
rate/min with age with age (age based) (age based)
dependent dependent <2 months ≥60/min <2 months ≥60/min
variation variation 2-12 months ≥50/min 2-12 months ≥50/min
1-5 years ≥40/min 1-5 years ≥40/min
>5 years ≥30/min >5 years ≥30/min
SpO2 on ≥94% ≥94% ≥90% <90%
room air
Grunting, - - - +/-
severe retraction
of chest
Lethargy, - - - +/-
somnolence
Seizure - - - +/-
 109

Spectrum of Pediatric COVID Cases

110
 111

Guide for using mask

Masks are not recommended for children aged 5 years and under
Children aged 6-11 years may wear a mask depending on the ability of child to use
a mask safely and appropriately under direct supervision of parents/guardians
Children aged 12 years and over should wear a mask under the same conditions as
adults
Ensure hands are kept clean with soap and water, or an alcohol-based hand rub,
while handling masks

Multi System Inflammatory Syndrome in Children (MIS-C)

New syndrome in children characterized by unremitting fever >38 C and
epidemiological linkage with SARS-CoV-2.

MIS-C with Kawasaki Disease (KD) phenotype is characterised

by fever, conjunctival redness, oropharyngeal findings (red and/
or cracked lips, strawberry tongue), rash, swollen and/or
erythematous hands and feet and cervical lymphadenopathy
 112

Use of steroids and anticoagulants

Steroids
•
Steroids are not indicated and are harmful in asymptomatic and mild cases of COVID-19
•
Indicated only in hospitalized severe and critically ill COVID-19 cases under strict
supervision
Steroids should be used at the right time, in right dose and for the right duration
•

Indications and recommended dose of corticosteroids – may be used in rapidly

•

progressive moderate and all severe cases

- Dexamethasone 0.15 mg/kg, maximum dose 6 mg once a day
or
- Methylprednisolone 0.75 mg/kg, maximum dose 30 mg once a day
•
Continue for 5-7 days and taper, up to 14 days, depending on clinical assessment on daily
•
Avoid steroids in first 3-5 days since onset of symptoms as it prolongs viral shedding

Anticoagulants
•
Not indicated routinely
All hospitalized children should be monitored for thrombosis; on suspicion, confirm by

:appropriate investigations and start on low molecular weight heparin in therapeutic doses
for period of 12 weeks with monitoring
Children already on anticoagulation therapy may continue same unless they develop active
bleeding.
Predisposing risk factors for development of thrombosis – personal history of venous

:
thrombotic events (VTE), family history of first-degree relative with VTE, presence of
central venous line, decreased mobility from baseline, burns, active malignancy, estrogen
therapy, flare of inflammatory disease, morbid obesity, severe dehydration, recent surgery
or trauma.
Prophylactic anticoagulant is indicated in following circumstances (a) strong personal or
family history of VTE, or (b) an indwelling central venous line and two or more additional
risk factors, or (c) four or more risk factors
 113

Management/treatment of ARDS
Mild ARDS

: - High flow nasal oxygen (start with 0.5 L/kg/min to begin with and increase to 2 L/kg/min
with monitoring) or non-invasive ventilation (BiPAP or CPAP) may be given
Moderate – Severe ARDS
- Consider crystalloid fluid bolus 10-20 ml/kg cautiously over 30-60 minutes with early
vasoactive support (epinephrine)
- Start antimicrobials within the first hour, after taking blood cultures, according to
hospital antibiogram or treatment guidelines
- Consider inotropes (milrinone or dobutamine) if poor perfusion and myocardial
dysfunction persists despite fluid boluses, vasoactive drugs and achievement of target
mean arterial pressure
- Hydrocortisone may be added if there is fluid refractory catecholamine resistant shock
(avoid if already on dexamethasone or methylprednisolone)
- Once stabilized, restrict IV fluids to avoid fluid overload
- Initiate enteral nutrition – sooner the better
- Transfusion trigger Hb <7g/dL if stable oxygenation and haemodynamics, and <10 g/dL
if refractory hypoxemia or shock

Stepwise investigations
 114
•
Tier 1 tests (may be done at Covid Care Centre, Dedicated Covid Health Centre): CBC,
complete metabolic profile (LFT/KFT/blood gas/glucose), CRP and/or ESR, SARS-CoV-2
serology and/or RT-PCR, blood culture Positive Tier 1 screen (both of these should be
present):
1. CRP >5 mg/L and/or ESR >40 mm/hour;
2. At least one of these: ALC <1000/µL, platelet count <150,000/µL, Na <135 mEq/L,
neutrophilia, hypoalbuminemia
•
Tier 2 tests (may be done at Dedicated Covid Hospital): Cardiac (ECG, echocardiogram, BNP,
troponin T); inflammatory markers (procalcitonin, ferritin, PT, PTT, D-Dimer, fibrinogen,
LDH, triglyceride, cytokine panel);
blood smear; SARS-CoV-2 serology
* Common tropical infections include malaria, dengue, enteric fever, rickettsial illness
(scrub typhus), etc.
Management

•
Appropriate supportive care is needed preferably in ICU for treatment of cardiac
dysfunction, coronary involvement, shock or multi-organ dysfunction syndrome (MODS)
- IVIG to be given slower (over up to 48 hrs) in children with cardiac failure/ fluid overload
- Taper steroids over 2-3 weeks with clinical and CRP monitoring
- Aspirin 3-5 mg/kg/day, maximum 75 mg/day in all children for 4-6 weeks (with platelet
count >80,000/µL) for at least 4-6 weeks or longer for those with coronary aneurysms
- Low molecular weight heparin (Enoxaparin) 1 mg/kg/dose twice daily s/c in >2 months
(0.75mg/kg/dose in <2 months) if patient has thrombosis or giant aneurysm with absolute
coronary diameter ≥8 mm or Z score ≥10 or LVEF <30%
- For children with cardiac involvement, repeat ECG 48 hourly & repeat ECHO at 7–14 days
and between 4 to 6 weeks, and after 1 year if initial ECHO was abnormal
 115

Psychiatry
Post-COVID Stress Disorder

separation anxiety during COVID-19

Separation anxiety is extreme distress that’s triggered by being apart from your
parents, primary caregivers or close companions. Although it may seem like a
childhood condition, separation anxiety can affect anyone.
116
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