COVID 19 -

All You need to know

By Dr Sonu Panwar
 Severe acute
2019 nCoV
respiratory
Wuhan City, China)
syndrome (SARS)

Incubation 4-6 days 2-14 days

Incidence Rare Current pandemic

80% resolution 15%

Prognosis 30% resolution
severe case 5%
70% severe
critical case
infection 10% fatal
4.2% fatal (as of
July 20, 2020,
based on identified
cases and may
change)

Clinical Fever > 37,8°C Asymptomatic

manifestation (100,0°F), Mild infection:
muscle ,pain, fever, dry cough,
lethargy, dry cough, muscles pain,
muscle cough, sore lethargy dehydration
throat, pain,
lethargy, malaise

Shortness of breath/ Severe infection:

pneumonia (direct high fever, shortness
viral or sencondary of breath, chest pain,
bectaria hemoptysis
The SARS-CoV-2 virion is approximately 125 nm in
diameter and its genome ranges from 26-32 kb, the
largest of all RNA viruses.

It has 4 structural proteins: spike (S), envelope (E),

membrane (M), and nucleocapsid (N).

S, E, and M proteins create the viral envelope.

N protein forms a complex with RNA
(nucleocapsid) and aids in the regulation of viral
RNA synthesis
M protein projects on the external surface of
the envelope, spans the envelope 3 times, and is
important in viral assembly.
E protein has an unclear function, although it
may aid in viral release.
S protein is a club-shaped surface projection,
giving the virus its characteristic crown-like
appearance on electron microscopy. It is
responsible for
Dr. Sonu Panwar
 Structural Protein of the SARS-CoV 2 Virion
In January 2020, population genetic analysis
concluded that SARS-CoV-2 had evolved into 2
separate genotypes:
L type: more aggressive and more prevalent
(approximately 70% of cases in the early
stages of outbreak; prevalence has since
decreased)
S type: evolutionary older, less common, and
less aggressive (approximately 30% of cases)
Dr. Sonu Panwar
SARS-CoV-2 attaches to the host cell by binding its S protein to
the receptor protein, angiotensin-converting enzyme 2
(ACE2). ACE2 is expressed by epithelial cells of the intestine,
kidney, blood vessels, and, most abundantly, in type II alveolar
cells of the lungs.
The human enzyme transmembrane protease, serine 2
(TMPRSS2), is also used by the virus for S protein priming and
to aid in membrane fusion. The virus then enters the host cell
via endocytosis.
SARS-CoV-2 affects the expression and presentation of ACE2,
contributing to its pathogenesis in the following ways:
Viral entry causes internalization of the receptor, leading
to its reduced availability on the cell surface. Because
ACE2 is a negative regulator of the RAAS system, its
downregulation directly affects cardiovascular function.
ACE2 inhibition induces ADAM17 gene expression,
leading to the release of tumor necrosis factor a (TNFa)
and cytokines such as interleukin 4 (IL-4) and interferon
y (IFNy). Dr. Sonu Panwar
 Increased cytokine concentrations activate further
proinflammatory pathways, leading to a cytokine storm.
ADAM-17 also promotes the cleavage of ACE2
receptors.
ADAM-17 also promotes the cleavage of ACE2 receptors.
SARS-CoV-2's affinity for ACE2 also results in direct and
acute injury to the lung, heart, endothelial cells, and,
potentially, other organs.

The expression of ACE2 is significantly increased through the

use of ACE inhibitors or angiotensin II receptor blockers
(ARBs). Contrary to initial reports, the American College of
Cardiology has noted that there are no data to support the
claim that ACE inhibitors and ARBs increase the risk of COVID-
19 infection, and recommends that patients who already use
these medications should continue to do so while further
studies are undertaken.

Dr. Sonu Panwar

Coronaviruses are zoonotic; that is, they are transmitted to
humans through animals. It is hypothesized that horseshoe
bats are the natural reservoir of SARS-CoV-2, since the
virus's genome is 96.2% identical to that of a bat coronavirus.
At this time, the intermediate host is still unknown.

Once in humans, the virus is transmitted when

respiratory droplets from coughing, sneezing, or talking
of infected individuals come into direct contact with the
mucous membranes of another individual, including the
eyes, nose, or mouth. In the air, larger droplets tend to drop
toward the ground, within 1 m (3 ft) of the infected person,
while smaller droplets can travel over 2 m (6 ft) and remain
viable in the air for up to 3 hours under certain conditions.

Other forms of transmission include the following:

Direct transmission through hand-to-face contact
from infected surfaces

Dr. Sonu Panwar

 Fecal—oral transmission is also believed to occur
(SARS-CoV-2 RNA has been detected in stool
specimens, but fecal—oral transmission has not been
clinically described).
Vertical transmission (mother-to-child) has not been
reported.

COVID-19 is not considered to be airborne, as coughing,

sneezing, and talking do not generate droplets small enough
to behave as aerosols. However, certain medical procedures
can generate virus-laden aerosol clouds, which put healthcare
personnel at a higher risk of becoming infected. (See
"Prevention" for more

Many factors can extend the range of respiratory droplet

dispersion past 2 m (6 ft). Certain actions, such as forced
expiration during yelling, singing, and exercise, can
increase the volume and distance that respiratory
droplets can travel.

Dr. Sonu Panwar

The reproductive number (R0), or the number of secondary
infections generated from 1 infected individual, is 2-2.5,
higher than for influenza (0.9-2.1). COVID-19 is highly
contagious for the following reasons:
Production of high viral loads
Efficient and prolonged shedding of virions from the
upper respiratory tract
1. Median duration of viral RNA shedding from
the upper respiratory tract is 20 days.
2. Viral shedding can outlast the resolution of
symptoms.
Asymptomatic individuals are also infectious, posing
a significant challenge for contagion prevention.
1. Viral loads peak before symptom onset, leading to
asymptomatic or presymptomatic spreading of the virus
and making symptom-based detection and isolation
ineffective.
2. Asymptomatic patients can produce high viral loads in
secretions of the upper respiratory tract and can shed the
virus for the same amount of time as symptomatic patients.
Dr. Sonu Panwar
SARS-CoV-2 can remain infectious on surfaces
outside of a host from a few hours to a few days.
1. Viral lifespan depends on the type of surface, temperature,
and humidity levels.
2. There is currently no evidence to suggest that COVID-19 can
be acquired from mail and packaged goods.

Dr. Sonu Panwar

The period of highest infectivity for symptomatic cases
ranges from 2 days before the onset of symptoms up to 3
days after their resolution (exact limits are still under
investigation).
Seroconversion, or the production of COVID-19- specific
antibodies, occurs after 7 days in 50% of patients and by day 14
in all patients. However, it is still unclear to what degree
antibodies provide a protective effect or if reinfection is
possible.

The first case of COVID-19 was traced back to the city of Wuhan,
China, in late November 2019, with an outbreak developing in
December. The virus quickly spread, with widespread ongoing
transmission occurring globally. Currently, COVID-19 has been
reported in every continent except Antarctica, with more
than 14 million people infected and over 600,000 dead
within the first 7 months of global spread. The COVID-19
outbreak was declared a Public Health Emergency of
International Concern on January 30, 2020, and a pandemic on
March 11, 2020, by the World Health Organization (WHO).

Dr. Sonu Panwar

Clinical Presentation
The incubation period for COVID-19 ranges from 2-
14 days, with an average of 5 days.
80% of infections are mild or asymptomatic
15% of infections are severe (requiring oxygen
therapy)
5% of infections are critical (requiring intensive
care unit [ICU] admission and ventilation)
The proportion of severe and critical-to-mild cases is
higher than in influenza infections.

The rate of severe, critical, and fatal cases varies

depending on location and age group. Children are
symptomatic in < 5% of cases and critical in <1%,
while up to 60% of elderly patients develop critical
infections.
Dr. Sonu Panwar
Asymptomatic cases:

These individuals can transmit the virus.

They represent > 50% of all infections (still
under investigation).
They do not develop any noticeable symptoms.
Anosmia, hyposmia, and dysgeusia have
been reported in many laboratory-confirmed
cases of patients who were otherwise
asymptomatic.
It has not been clearly determined how long
asymptomatic individuals remain contagious
after initial infection.
These individuals can present radiological and
laboratory findings characteristically found in
symptomatic COVID-19 patients

Dr. Sonu Panwar

Mild cases:

May present with dry cough and moderate

fever
Include common flu-like symptoms such as
fatigue, malaise, myalgia, runny nose, nasal
congestion, and sore throat
Less frequently experience diarrhea, nausea,
vomiting, diffuse abdominal pain, productive
cough, headache, and muscle or joint pain •
Dermatologic symptoms have been reported,
including maculopapular, urticarial, and
vesicular eruptions, transient livedo reticularis,
perniosis-like red or purple tender nodules on
the distal digits ("COVID toes")
Have a recovery time of approximately 2
weeks
Dr. Sonu Panwar
There are no specific clinical features that can
reliably distinguish COVID-19 from other viral
respiratory infections such as influenza, SARS,
pneumonia, or tuberculosis.

Dr. Sonu Panwar

Severe cases and complications:
Approximately 1 in 6 people with COVID-19
experience clinical deterioration and/or
develop a complication after an average of 5-7
days.
Median time from onset of symptoms to the
onset of critical care/ICU transfer is 8-9 days.
Patients develop dyspnea, high fever, chest
pain, hemoptysis, anorexia, and/or respiratory
crackles, which indicates the development of
pneumonia (most frequent complication
in severe cases).
Respiratory failure from acute respiratory
distress syndrome (ARDS) is the most
common finding in critical cases.
Recovery time is approximately 3-6 weeks.
Dr. Sonu Panwar
Common complications of COVID-19 include
interstitial pneumonia, hypoxemic respiratory
failure/ARDS, acute kidney injury, and coagulopathy.
Other complications include acute cardiac injury,
cardiomyopathy, arrhythmia, liver dysfunction, sepsis, septic
shock, and multi-organ failure.
Risk factors for a severe infection and development of
complications from COVID-19 (from highest to lowest risk)
include the following:
Age > 65 years
Living in a nursing home or long-term care facility
Chronic diseases:
1. Chronic lung disease or moderate to severe
asthma
2. Cardiovascular disease
3. Immunosuppression (from long-term steroid
use, cancer, AIDS/HIV infection, congenital
immunodeficiency, organ transplants,
immunosuppressants, etc.) Dr. Sonu Panwar
 3.
4. Severe obesity (BMI > 40)
5. Diabetes mellitus, chronic kidney disease
undergoing dialysis, cerebrovascular disease,
and liver rlicaaca AP&

Pregnancy
1. Risk of infection is the same as in non-
pregnant individuals.
2. A higher risk of severe illness in pregnant
individuals is assumed due to the behavior of
similar respiratory infections, such as SARS
and influenza.
Refractory cases:
Nearly 50% of COVID-19 patients do not achieve clinical
and radiological remission within 10 days of hospitalization.
Male patients, older patients, individuals with anorexia, and
those with no/low fever at the time of admission have a
higher risk of presenting with a refractory progression.
Dr. Sonu Panwar
 COVID-19 in children
The clinical presentation and severity of cases of COVID-
19 in patients < 18 years old is different from that of
adults. Children are at lower risk of developing severe or
critical infections, and complications appear to be
milder.
In children:
Approximately 55% of cases are asymptomatic or
mild
40% of cases are moderate (pneumonia and/or
abnormal chest imaging)
5% of cases are severe (dyspnea and hypoxia,
requiring oxygen therapy)
<1% of cases are critical (ARDS, respiratory
failure, shock, or multi-organ failure requiring ICU
transfer)
Dr. Sonu Panwar
Pediatric inflammatory multisystem syndrome is a
newly discovered complication occurring in
pediatric patients. The case definition by the Royal
College of Paediatrics and Child Health includes the
following criteria:
A child presenting with persistent fever ( 4 days),
inflammation (neutrophilia, elevated C-reactive
protein, and lymphopenia) and evidence of single-
or multi-organ dysfunction (shock or cardiac,
respiratory, renal, gastrointestinal, or neurological
disorder)
o This may include children fulfilling full or partial
criteria for Kawasaki disease.
Exclusion of any other microbial cause, including
bacterial sepsis, staphylococcal orstreptococcal
shock syndromes, and infections associated with
myocarditis (enterovirus)

Dr. Sonu Panwar

 SARS-CoV-2 PCR testing may be positive or
negative.
Respiratory symptoms are only present in half of these
patients. Abdominal symptoms such as pain, vomiting,
or diarrhea are also common.
Reverse transcription polymerase chain reaction
(RT-PCR) is currently the only test being used to
confirm cases of acute COVID-19 infection and
should be performed once a person under investigation
(PUI) is identified according to the priorities outlined
below. A positive test for SARS-CoV-2 generally confirms
the diagnosis of COVID-19, regardless of the patient's
clinical status. The specimens used for testing include the
following:
Nasopharyngeal (NP) or oropharyngeal (OP) swab
NP is the first choice. OP swabs are acceptable
only if NP swabs are not available.
Dr. Sonu Panwar
 Nasal mid-turbinate swab or swab of anterior
nares (nasal swab)
Nasopharyngeal wash/aspirate or nasal wash /
aspirate specimen
Sputum (for patients with productive cough;
inducing is not recommended)

Bronchoalveolar lavage, tracheal aspirate,

pleural fluid, and lung biopsy (for patients with
critical infections receiving invasive mechanical
ventilation)

RT-PCR testing can be negative initially. If suspicion of

COVID-19 remains, the patient should be retested every
2-3 days. In severe cases, swabs from the upper
respiratory tract may be negative, while specimens from
the lower respiratory tract are positive. RT-PCR tests can
also yield false negatives in 20%-30% of cases.
Dr. Sonu Panwar
Nasopharyngeal swab: Insert swab into a nostril
parallel to the palate, and carefully slide it forward
until a soft resistance is felt. Swab should reach a
depth equal to distance from nostrils to outer
opening of the ear. Rotate for several seconds to
absorb secretions, and then slowly remove.
1. Oropharyngeal swab: Insert swab into the oral cavity
without touching the gums, teeth, and tongue. A tongue
depressor may be used. Swab the posterior pharyngeal
wall using a rotatory motion.
2. Place swabs immediately into sterile tubes containing 2-3
ml of viral transport media. If both swabs are collected,
they should be combined into a single vial.
3. Carefully leverage the swab against the tube rim to break
the shaft at the scoreline.
4. Store specimens at 2-8°C for up to 72 hours after
collection. If a delay in testing/shipping is expected, store
specimens at -70°C or below. Use only synthetic fiber
swabs with plastic shafts. Calcium alginate swabs or swabs
with wooden shafts may inactivate the virus and inhibit PCR
testing.
Dr. Sonu Panwar
Due to limited availability of testing in certain countries,
a diagnosis of COVID-19 can be made
presumptively in the presence of a compatible
clinical presentation with an exposure risk,
particularly when there is no other evident cause of the
symptoms. Testing for other causes of respiratory
illness, such as influenza, is strongly encouraged in
these cases. However, a positive test result for another
respiratory agent does not rule out coinfection.

During an ongoing COVID-19 outbreak, patients with

suspected infection who do not present with severe
symptoms are encouraged to call prior to presenting to
a healthcare facility for evaluation and testing.
Laboratory testing of a PUI should be prioritized as
follows according to the CDC (only in a state of
emergency due tc shortages or limited testing capacity):
Dr. Sonu Panwar
High priority:
1. Hospitalized patients with symptoms
2. Healthcare facility workers, workers in
congregate living settings, and first
responders with symptoms
3. Residents in long-term care facilities or other
congregate living settings, including prisons
and shelters, with symptoms
Priority:
o Persons with signs and symptoms compatible with
COVID-19
o Persons without symptoms who are prioritized by
health departments or clinicians for any reason, including
but not limited to:
■ Public health monitoring
■ Sentinel surveillance
■ Screening of other asymptomatic individuals
according to state and local plans Dr. Sonu Panwar
Patients with COVID-19 present with the following
laboratory and radiological findings. These are more
pronounced and common in severe and critical cases
but can also be present even in asymptomatic
infections:
White blood cell count: leukopenia, leukocytosis,
and lymphopenia (most common)
Inflammatory markers: I LDH and ferritin
Liver markers: i AST and ALT
Chest X-ray and computed tomography (CT):
o Not recommended for initial evaluation; reserved
for hospitalized patients or symptomatic patients
with specific clinical indications
o Common findings include ground-glass opacities
(GG0s), multiple areas of consolidation, "crazy
paving appearance" (GGOs -F inter-/intralobular
septal thickening), and bronchovascular thickening.
_
Dr. Sonu Panwar
Asymptomatic or presymptomatic infection:
individuals who test positive for SARS-CoV-2 but
have no symptoms
Mild case: individuals who present signs and
symptoms without dyspnea or abnormal imaging
Moderate case: individuals who have evidence of
lower respiratory disease due to signs and
symptoms or radiological findings, but maintain a
saturation of oxygen (Sa02) > 93% on room air at
sea level
Severe case: individuals who have a respiratory
rate > 30 breaths per minute, Sa02 5 93% on room
air at sea level, ratio of arterial partial pressure of
oxygen to fraction of inspired oxygen (Pa02/F102)
< 300, or infiltrates covering > 50% of the lungs
Critical case: individuals who have respiratory
failure, septic shock, and/or multiple organ
dysfunction
Dr. Sonu Panwar
There are insufficient data to recommend the use of
any antiviral or immunomodulatory therapy in patients
with mild cases or asymptomatic or presymptomatic
infections of COVID-19. It is recommended that these
patients begin supportive at-home care. In the case of
antipyretics, the use of ibuprofen is now
considered safe according to the latest WHO
advice (March 17, 2020).

In the outpatient setting, it is important to seek

professional medical assistance if any of the following
emergency warning signs develop:

Difficulty breathing or shortness of breath

Persistent pain or pressure in the chest
Confusion or inability to arouse
Cyanosis (bluish tint to lips or face)

Dr. Sonu Panwar

Most patients with moderate-to-severe cases of
COVID-19 require hospitalization, with critical cases
requiring admission to an ICU. However, the decision
to monitor a patient in the inpatient setting should be
made on a case-by-case basis. Once hospitalized,
supportive care and acute measures should be
applied as necessary, and should include the
following:
Oxygen therapy using nasal cannula or high-flow oxygen
for patients who develop respiratory distress, hypoxemia, or
shock
Empiric antimicrobials if sepsis or secondary pneumonia
is strongly suspected
Advanced oxygen tnerapy, ventilatory support, and
conservative fluid management in the case of ARDS or
respiratory failure
Fluid bolus and vasopressors in the case of septic shock
Clinical management of other comorbidities and
nosocomial complication
Dr. Sonu Panwar
The mortality rate of COVID-19 varies across
different countries and age groups, with a global
average crude rate of 4.2%; there
The ongoing pandemic makes it difficult to determine
an accurate mortality rate at this time. The rate is
assumed to be lower than the current estimate due to
many undetected cases (lack of widespread testing in
many countries and asymptomatic individuals not
seeking to be tested). Epidemiologic reports from the
United States suggest the following fatality rates per
age group: 10%-27% for individuals 85 years of age,
3%-11% for individuals 65-84 years of age,1%-3% for
individuals 55-64 years of age, and <1% for individuals s
54 years of age.

Causes of death in COVID-19 patients include

respiratory failure, multi-organ failure, and
hypotensive shock.
Dr. Sonu Panwar
Several clinical trials are currently being performed to
further the development and research of antiviral drugs
against SARS-CoV-2. However, there are no data
available as of July 20, 2020, to support the
recommendation of any of the following
investigational therapeutics for patients with
confirmed or suspected COVID-19:
Remdesivir is reported to have in-vitro activity
against SARS-CoV and MERS-CoV by entering
nascent viral RNA chains and producing premature
termination.
1. The Food and Drug Administration (FDA)
issued an emergency use authorization for
hospitalized children and adults with severe
COVID-19.

Dr. Sonu Panwar

Chloroquine and hydroxychloroquine, widely
used antimalarial drugs, are reported to block viral
entry by inhibiting virus/cell fusion.

1. The combined use of hydroxychloroquine and

azithromycin, a macrolide antibiotic, was
reported to reduce the detection of SARS-CoV-
2 RNA in upper respiratory tract specimens.
Caution is advised when administering these
drugs in patients with chronic medical
conditions as both are associated with QT
prolongation and may lead to life-threatening
arrhythmia or sudden death.
2. The FDA issued an emergency use
authorization for hospitalized adolescents or
adults with COVID-19 when participation in
clinical trials is not feasible.

Dr. Sonu Panwar

Convalescent plasma with a SARS-CoV-2-specific
antibody (IgG) has been reported, in preliminary
studies, to improve clinical status.
Lopinavir-ritonavir, a combined protease inhibitor
usually used for HIV infection, was reported as having
in-vitro inhibitory activity against SARS-CoV. However,
no benefit was observed in hospitalized adult
patients with severe Covid-19 in trials conducted in
China.
Tocilizumab is an anti-IL-6 receptor agent used for
rheumatoid arthritis. It is currently being investigated
in patients with severe COVID-19 presenting with
high IL-6 levels.
Meplazumab is an anti-CD147 monoclonal antibody
that has shown in-vitro inhibitory activity against
SARS-CoV-2.
Camostat mesilate (CM), a TMPRSS2 inhibitor, is
reported to block viral entry by inhibiting S protein
priming. Dr. Sonu Panwar
It is now a global recommendation that all individuals
should help prevent the spread of COVID-19 infection.
General recommendations include the following:
Home isolation and quarantine: avoidance of
public/crowded areas whenever possible to minimize
the chance of exposure or transmission 0 Upon
returning from international travel, individuals should
practice home isolation for 14 days and monitor the
possible onset of symptoms.
Respiratory hygiene: coughs and sneezes should be
covered with a tissue or the inner elbow.
Washing hands regularly for at least 20 seconds
with soap and water or with an alcohol-based
hand sanitizer that contains at least 60% alcohol
Social distancing: maintaining 1-2 m (approximately
3-6 ft) distance from other people
o Certain actions, such as forced expiration during yelling,
singing, and exercise, can increase the volume and
distance that respiratory droplets can travel.
Dr. Sonu Panwar
The use of face masks is now recommended for
the general population.

1. Face masks help prevent the wearer from

becoming infected and, more importantly,
prevent the wearer from transmitting the
disease (also known as "source control").
2. For healthcare personnel, PPE and National
Institute for Occupational Safety and Health—
approved N95 disposable filtering facepiece or
higher-level respirators, such as a powered air-
purifying respirator, are recommended when
providing care for patients with suspected or
confirmed COVID-19 due to higher exposure to
infected individuals as well as AGPs. AGPs
include the following:

Dr. Sonu Panwar

well as AGPs. AGPs include the following:

■ Open suctioning of airways

■ Sputum induction
■ Cardiopulmonary resuscitation
■ Endotracheal intubation and extubation
■ Non-invasive ventilation (eg, BiPAP, CPAP)
■ Bronchoscopy
■ Manual ventilation
It is still unclear how long SARS-CoV-2 can survive on
human hair, but healthcare personnel is encouraged to
cover hair with a disposable or surgical cap.

Isolation and quarantine can be discontinued only

after the following criteria have been met:

Dr. Sonu Panwar

 At-home and hospitalized symptomatic cases:

1. Negative results of PCR testing obtained from at

least 2 consecutive nasopharyngeal swab specimens
collected z 24 hours apart OR
2. At least 3 days have passed since the resolution of
fever without the use of antipyretics and
improvement in respiratory symptoms AND
3. At least 10 days have passed since the onset of
symptoms
• Asymptomatic cases:

1. Negative results of PCR testing obtained from at

least 2 consecutive nasopharyngeal swab specimens
collected z 24 hours apart OR
2. At least 10 days have passed since the first positive
COVID-19 diagnostic test ..........
Dr. Sonu Panwar
Vaccine

Currently, there is no FDA-approved vaccine available to

prevent COVID-19. A phase 1 clinical trial evaluating
an investigational vaccine began on March 16,
2020, in the Kaiser Permanente Washington Health
Research Institute in Seattle, Washington. The vaccine is
called mRNA-1273 and is designed .

The Bacille-Calmette-Guerin (BCG) vaccine, primarily

used for the prevention of tuberculosis, is being
evaluated for the prevention of COVID-19. Studies have
reported that BCG immunization offers protection
against various non-mycobacterial viruses, including
herpes and influenza viruses. Clinical trials are underway
to evaluate its efficiency against SARS-CoV-2.

Dr. Sonu Panwar

Thank You!
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