variant group.

The receptor-binding gene region

appears to be very similar to that of the SARS
CoV and it is believed that the same receptor
would be used for eel I entry.17

4.1 Virion structure a nd its

genome
Coronaviruses are structurally enveloped,
belonging to the positive-strand RNA viruses
I
category that has the largest known genomes
of RNA. The structures of the coronavirus are
more spherical in shape, but their structure
has the potential to modify their morphology in
response to environmental conditions, being
pleomorphic. The capsular membrane which
represents the outer envelope usually has
glycoprotein projection and covers the nucleus,
comprising a matrix protein containing a
positive-strand RNA. Since the structure
possesses 5'-capped and 3'-polyadenylated
ends, it remains identical to the cellular
mRNAs. 18 The structure is comprised of
hemagglutinin esterase (HE) (present only in
some beta-coronaviruses), spike (5), small
membrane (E), membrane (M) and nucleocapsid
(N), as shown (Figure 1). The envelope
containing glycoprotein is responsible for
attachment to the host cell, which possesses
the primary anti-genie epitopes mainly those
specimens, like bronchoalveolar lavage fluid,
sputum, nasal swabs, fibrobronchoscope brush
biopsy specimens, pharyngeal swabs, feces, and
blood (246).
The presence of SARS-CoV-2 in fecal samples
has posed grave public health concerns. In addition
to the direct transmission mainly occurring via
droplets of sneezing and coughing, other routes, such
as fecal excretion and environmental and fomite
contamination , are contributing to SARS-CoV-2
transmission and spread (249-252). Fecal excretion
has also been documented for SARS-CoV and
MERS-CoV, along with the potential to stay viable
in situations aiding fecal-oral transmission. Thus,
SARS-CoV-2 has every possibility to be transmitted
through this mode. Fecal-oral transmission of SARS
CoV-2, particularly in regions having low standards
of hygiene and poor sanitation, may have grave
consequences with regard to the high spread of this
virus . Ethanol and disinfectants containing chlorine
or bleach are effective against coronaviruses (249-
252). Appropriate precautions need to be followed
strictly while handling the stools of patients infected
with SARS-CoV-2. Biowaste materials and sewage
from hospitals must be adequately disinfected,
treated, and disposed of properly. The significance
of frequent and good hand hygiene and
07:25 (Ml 0 '\ . •..id i
consolidation. It is also abnormal in
asymptomatic patients/ patients with
no clinical evidence of lower
respiratory tract involvement. In fact,
abnormal CT scans have been used to
diagnose COVID-19 in suspect cases
with negative molecular diagnosis;
many of these patients had positive
molecular tests on repeat testing [22].

Differential Diagnosis [21]

The differential diagnosis includes all
types of respiratory viral infections
[influenza, pa rainfluenza, respiratory
syncytial virus (RSV), adenovirus,
human metapneumovirus, non COVID-
19 coronavirus], atypical organisms
(mycoplasma, chlamydia) and
bacterial infections. It is not possible
to differentiate COVID-19 from these
infections clinically or through routine
lab tests. Therefore travel history
becomes important. However, as the
epidemic spreads, the travel history
in Yunnan. This novel bat virus, denoted 'RmYN02 ',
is 93.3% identical to SARS-CoV-2 across the genome.
In the long l ab gen e, it exhibits 97.2% identity to
SARS-CoV-2, which is even higher than for RaTG13
28
(REF. ) . In addition to RaTG13 and RmYN02 ,
phyloge netic analysis shows that bat coronaviruses
ZC45 and ZXC2 lpreviously detected in Rhinolop
hus pu sillu s bats from eastern China also fall into the
SARS-CoV-2 lineage of the subgenus Sarbecovirus36
(FIG. 2) . The dis covery of diverse bat coronavir uses
closely related to SARS-CoV-2 suggests that bats are
possible reservoirs ) of SARS-CoV-2 (REF.37 .
Nevertheless, on the basis of current findings, the
divergence between SARS-CoV-2 and related bat
coronaviruseslikely represents more than 20 years of
sequence evolution , suggesting that these bat
coronaviruses can be regarded only as the likely
evolu- tionary precursor of SARS-CoV-2
) but not as
the direct progenitor of SARS-CoV-2 (REF.38 .
Beyon d bats, pangolins are another wildlife host
probablylinked with SARS-CoV-2.Multiple SARS-CoV-
2- related viruses have been identified in tissues of
Malayan pangolins smuggled from Southeast Asia into
southern China from 2017 to 2019. Theseviruses from
pangolins independently seized by Guangxi and
Guangdong pro
vincial customs belong to two distinct sublineages39 41
- •

Th e Guangd ong strains, which were isolated or

sequenced by different research groups from smug
gled pangolins, have 99.8% sequence identity with
each other41 • They are very closely related to SARS-
CoV-2, exhibiting 92.4% sequence similarity.
Notably, the RBD of Guangdong pangolin
coronaviruses is highly similar to that of SARS-CoV-
2. The receptor -binding motif (RBM; which is part
of the RBD) of these viruses has only one amino acid
variation from SARS-CoV-2, and it is identical to that
of SARS-CoV-2 in all five critical
07:25 (Ml 0" •

of persistent local transmission or

contact with patients with similar
travel history or those with confirmed
COVID-19 infection. However cases
may be asymptomatic or even
without fever. A confirmed case is a
suspect case with a positive
molecular test.

Specific diagnosis is by specific

molecular tests on respiratory samples
(throat swab/ nasopharyngeal swab/
sputum/ endotrache al aspirates and
bronchoalveolar lavage). Virus may
also be detected in the stool and in
severe cases, the blood. It must be
remembered that the multiplex PCR
panels currently available do not
include the COVID-19. Commercial
tests are also not available at present.
In a suspect case in India, the
appropriate sample has to be sent to
designated
ref erence labs in India or the National
Institute of Virology in Pune. As the
epidemic progresses, commercial tests

• •
(using suitable animal models) should be conducted
to evaluate the risk of future epidemics . Presently,
licensed antiviral drugs or vaccines against SARS
CoV, MERS-CoV, and SARS-CoV-2 are lacking.
However, advances in designing antiviral drugs and
vaccines against several other emerging diseases will
help develop suitable therapeutic agents against
COVID-19 in a short time. Until then, we must rely
exclusively on various control and prevention
measures to prevent this new disease from becoming
a pandemic.
or even die, whereas most young p eople and
children have only m ild diseases (non-pn
eum onia or m ild 82
9,
pneumonia) or are asymptomatic . Notably, the
81
, risk
of disease was not higher for pregnant women.
However, evidence of transplacental transmission of
SARS-CoV-2 from an infected mother to a neonate
was reported ,
although it was an isolated case83 On infection , the
84
' .

most comm on symptoms are fever, fatigue and dry

cough 13,6o,so,si . Less common symptoms include
sputum production,headache,haemoptysis, diarrhoea,
anorexia, sore throat, chest pain, chills and nausea
and vomiting in studies of patients in China 13'6o,so,si .
Self-reported olfac tory and taste disorders were also
reported by patients in Italy85• Most people showed
signs of diseases after an incubation period of 1-14
days (most commonly around 5 days), and dyspnoea
and pneumonia developed within a m.edian • time of 8
days from illness onset9
In a report of 72,314 cases in Chin a, 81% of the
cases were classified as mild, 14% were severe cases
that required ventilation in an intensive care unit
(ICU) and a 5% were critical (that is, the patients had
respiratory failure, septic shock and/ or multiple
organ dysfunction
or failure)9 On admission, ground-glass opacity was
86
' •
the most common radiologic finding on chest
computed tomography ' (CT) 13 6o,so,si. Most patients
also developed marked lymphopenia, similar to what
was observed in patients with SARS and MERS, and
non -survivors devel oped severer lymphopenia
' over
time 13 6o,so,si . Compared
with non-ICU patients, ICU patients had higher levels
,.. .. .. . .. . .. ..
13 CONVALE SCENT PLASMA
THE RAPY
Guo Yanhong, an official with the National
Health Commission (NHC), stated that
convalescent plasma therapy is a significant
method for treating severe COVI D-19 patients.
Among the COVID-19 patients currently
receiving convalescent plasma therapy in the
virus-hit Wuhan, one has been discharged from
hospital,as reported by Chinese science
authorities on Monday, 17th February 2020 in
Beijing. The first dose of convalescent plasma
from a COVID-19 patient was collected on 1st
and 9th February 2020 from a severely ill
patient who was given treatment at a hospital in
jiangxi a District in Wuhan . The presence of the
virus in patients is minimised by the antibodies
in the convalescent plasma . Guiqiang stated
that donating plasma may cause minimal harm
to the donor and that there is nothing to be
worried about. Plasma donors must be cured
patients and discharged from hospital. Only
plasma is used, whereas red blood cells (RBC),
white blood cells (WBC) and blood platelets are
transfused back into the donor's body. Wang
alleged that donor's plasma will totally improve
to its initial state after one or 2 weeks from the
day of plasma donation of around 200 to 300
millilitres.61
It;\t mg 1 Ht;r ile chn1cians
must be on the look-out for the possible occurrence
of atypical clinical manifestations to avoid the
possibility of missed diagnosis. The early
transmission ability of SARS-CoV-2 was found to be
similar to or slightly higher than that of SARS-CoV,
reflecting that it could be controlled despite
moderate to high transmissibility (84).
Increasing reports of SARS-CoV-2 in sewage and
wastewater warrants the need for further
investigation due to the possibility of fecal-oral
transmission. SARS-CoV-2 present in environmental
compartments such as soil and water will finally end
up in the wastewater and sewage sludge of treatment
plants (328). Therefore, we have to reevaluate the
current wastewater and sewage sludge treatment
procedures and introduce advanced techniques that
are specific and effective against SARS-CoV-2.
Since there is active shedding of SARS-CoV-2 in the
stool, the prevalence of infections in a large
population can be studied using wastewater-based
epidemiology. Recently, reverse transcnptlon
quantitative PCR (RT-qPCR) was used to enumerate
the copies of SARS-CoV-2 RNA concentrated from
wastewater collected from a wastewater treatment
plant (327). The calculated viral RNA copy numbers
determine the number of infected individuals. The
07:27 (Ml 0" .

Preventi on [21, 30]

Since at this time there are no
approved treatments for this infection,
prevention is crucial. Several
properties of this virus make
prevention difficult namely, non
specific features of the disease, the
infectivity even before onset of
symptoms in the incubation period,
transmission from asymptomatic
people, long incubation period, tropism
for mucosal surfaces such as the
conjunctiva, prolonged duration of the
illness and transmission even after
clinical recovery.

Isolation of confirmed or suspected

cases with mild illness at home is
recommended. The ventilation at
home should be good with sunlight to
allow for destruction of virus. Patients
should be asked to wear a simple
surgical mask and practice cough
hygiene .
• •
07:25 (Ml 0" .

Epidemiology and Pathogenesis

[10, 11]
All ages are susceptible. Infection is
transmitted through large droplets
generated during coughing and
sneezing by symptomatic patients but
can also occur from asymptomatic
people and before onset of symptoms
[9]. Studies have shown higher viral
loads in the nasal cavity as compared
to the throat with no difference in
viral burden between symptomatic
and asymptomatic people [12].
Patients can be infectious for as long
as the symptoms last and even on
clinical recovery. Some people may
act as
super spreaders; a UK citizen who
attended a conf erence in Singapore
infected 11other people while staying
in a resort in the French Alps and upon
return to the UK [6]. These infected
droplets can spread 1-2 m and deposit
• •
system (30).
Bovine coronaviruses (BoCoVs) are known to
infect several domestic and wild ruminants (126).
BoCoV inflicts neonatal calf diarrhea in adult cattle,
leading to bloody diarrhea (winter dysentery) and
respiratory disease complex (shipping fever) in cattle
of all age groups (126). BoCoV-like viruses have
been noted in humans, suggesting its zoonotic
potential as well (127). Feline enteric and feline
infectious peritonitis (FIP) viruses are the two major
feline CoVs (128), where feline CoVs can affect the
gastrointestinal tract, abdominal cavity (peritonitis),
respiratory tract, and central nervous system (128).
Canines are also affected by CoVs that fall under
different genera, namely, canine enteric coronavirus
1n Alpha coronavirus and canine respiratory
coronavirus in Betacoronavirus, affecting the enteric
and respiratory tract , respectively (129, 130). IBV,
under Gammacoronavirus, causes diseases of
respiratory, urinary, and reproductive systems, with
substantial economic losses in chickens (131, 132).
In small laboratory animals, mouse hepatitis virus,
rat sialodacryoadenitis coronavirus, and guinea pig
and rabbit coronaviruses are the major CoVs
associated with disease manifestations like enteritis,
hepatitis , and respiratory infections (10, 133).
Swine acute diarrhea syndrome coronavirus
07:25 (Ml 0 '\ • •..id i
including 1L2, lL 7, lLlU, GCS.F, l.PlO,
MCP1, MIP1A, and TNFa [15]. The
median time from onset of symptoms
to dyspnea was 5 d, hospitalization 7 d
and acute respiratory distress
syndrome (ARDS) 8 d. The need for
intensive care admission was in 25-
300/o of affected patients in published
series. Complications witnessed
included acute lung injury, ARDS,
shock and acute kidney injury.
Recovery started in the 2nd or 3rd wk.
The median duration of hospital stay in
those who recovered was 10 d.
Adverse outcomes and death are more
common in the elderly and those with
underlying co-morbidities (50-75°/o of
fatal cases). Fatality rate in hospitalized
adult patients ranged from 4 to 11°/o.
The overall case fatality rate is
estimated to range between 2 and 3°/o
[2].

Interestingly, disease in patients

outside Hubei province has been
• •
absence of this protein 1s related to the altered
virulence of coronaviruses due to changes in
morphology and tropism (54). The E protein consists
of three domains, namely, a short hydrophilic amino
terminal, a large hydrophobic transmembrane
domain, and an efficient C-terminal domain (51).
The SARS-CoV-2 E protein reveals a similar amino
acid constitution without any substitution (16).

N Protein
The N protein of coronavirus is multipurpose.
Among several functions, it plays a role in complex
formation with the viral genome, facilitates M
protein interaction needed during virion assembly,
and enhances the transcription efficiency of the virus
(55, 56). It contains three highly conserved and
distinct domains, namely, an NTD, an RNA-binding
domain or a linker region (LKR), and a CTD (57).
The NTD binds with the 3' end of the viral genome,
perhaps via electrostatic interactions, and is highly
diverged both in length and sequence (58). The
charged LKR is serine and arginine rich and is also
known as the SR (serine and arginine) domain (59).
The LKR is capable of direct interaction with in vitro
RNA interaction and is responsible for cell signaling
(60, 61). It also modulates the antiviral response of
the host by working as an antagonist for interferon
07:25 (Ml 0" •

··
Interestingly, disease in patients
outside Hubei province has been
reported to be milder than those from
Wuhan [17]. Similarly, the severity
and case fatality rate in patients
outside China has been reported to be
milder [6]. This may either be due to
selection bias wherein the cases
reporting from Wuhan included only
the severe cases or due to
predisposition of the Asian population
to the virus due to higher expression of
ACE 2 receptors on the
respiratory mucosa [11].

Disease in neonates, infants and

children has been also reported to be
significantly milder than their adult
counterpa rts. In a series of 34 children
admitted to a hospital in Shenzhen,
China between January 19th and
February 7th, there were 14 males and
20 females. The median age was 8 y 11
mo and in 28 children the infection
was linked to a family member and 26
07:27 (Ml 0" •
prongs, face mask, high flow nasal
cannula (HFNC) or non-invasive
ventilation is indicated. Mechanical
ventilation and even extra corporeal
membrane oxygen support may be
needed. Renal replacement therapy
may be needed in some. Antibiotics
and antifungals are required if co
infections are suspected or proven. The
role of corticosteroids is unproven;
while current international consensus
and WHO advocate against their use,
Chinese guidelines do recommend
short term therapy with low-to
moderate dose corticosteroids in
COVID-19 ARDS [24, 25]. Detailed
guidelines for critical care
management for COVID-19 have
been
published by the WHO [26]. There is,
as of now, no approved treatment for
COVID-19. Antiviral drugs such as
ribavirin, lopinavir-ritonavir have
been used based on the experience
with SARS and MERS. In a historical
• •
th is emerging virus will establish a niche in hum ans
and coexist with us for a long • Before clinically
time 166
approved vaccines are widely available, there is no
bet ter way to protect us from SARS-CoV-2 than
personal preventive behaviours such as social
distancing and wearing masks, and public health
measures, including active testing, case tracing and
restrictions on social gatherings. Despite a flood of
SARS-CoV-2 research published every week,
current knowledge of this novel coronavirus is just
the tip of the iceberg. The animal origin and cross-
species infection route of SARS-CoV-2 are yet to be
uncovered. The molecular mechanisms of SARS-
CoV-2 infection pathogen esis and virus-host
(173, 174). Hence, knowledge and understanding of
S protein-based vaccine development in SARS-CoV
will help to identify potential S protein vaccine
candidates in SARS-CoV-2. Therefore, vaccine
strategies based on the whole S protein, S protein
subunits, or specific potential epitopes of S protein
appear to be the most promising vaccine candidates
against coronaviruses. The RBD of the S1 subunit of
S protein has a superior capacity to induce
neutralizing antibodies. This property of the RBD
can be utilized for designing potential SARS-CoV
vaccines either by using RED-containing
recombinant proteins or recombinant vectors that
encode RBD (175). Hence, the superior genetic
similarity existing between SARS-CoV-2 and SARS
CoV can be utilized to repurpose vaccines that have
proven in vitro efficacy against SARS-CoV to be
utilized for SARS-CoV-2. The possibility of cross
protection 1n COVID-19 was evaluated by
comparing the S protein sequences of SARS-CoV-2
with that of SARS-CoV. The comparative analysis
confirmed that the variable residues were found
concentrated on the S1 subunit of S protein, an
important vaccine target of the virus (150). Hence,
the possibility of SARS-CoV-specific neutralizing
antibodies providing cross-protection to COVID-19
might be lower. Further genetic analysis is required
07:25 (Ml 0" •

··
on surfaces. The virus can remain
viable on surfaces for days in
favourable atmospheric conditions but
are destroyed in less than a minute by
common disinfectants like sodium
hypochlorite, hydrogen peroxide etc.
[13]. Infection is acquired either by
inhalation of these droplets or touching
surfaces contaminated by them and
then touching the nose, mouth and
eyes. The virus is also present in the
stool and contamination of the water
supply and subsequent transmission
via aerosoliz ation/feco oral route is
also hypothesized [6]. As per current
information, transplacental
transmission from pregnant women to
their fetus has not been described
[14]. However, neonatal disease due
to post natal transmission is described
[14].
•
The incubation period varies from 2 to
14 d [median 5 d]. Studies have
identified angiotensin receptor 2
( L\ r l=' _ ) '-' th o ror ontn r th rn11rrh u rh i rh
only a matter of time before another zoonotic
coronavirus results in an epidemic by jumping the
so-called species barrier (287).
The host spectrum of coronavirus increased when
a novel coronavirus, namely, SWl, was recognized
in the liver tissue of a captive beluga whale
(Delphinapterus leucas) (138). In recent decades,
several novel coronaviruses were identified from
different animal species. Bats can harbor these
viruses without manifesting any clinical disease but
are persistently infected (30). They are the only
mammals with the capacity for self-powered flight,
which enables them to migrate long distances, unlike
land mammals. Bats are distributed worldwide and
also account for about a fifth of all mammalian
species (6). This makes them the ideal reservoir host
for many viral agents and also the source of novel
coronaviruses that have yet to be identified. It has
become a necessity to study the diversity of
coronavirus in the bat population to prevent future
outbreaks that could jeopardize livestock and public
health. The repeated outbreaks caused by bat-origin
coronaviruses calls for the development of efficient
molecular surveillance strategies for studying
Betacoronavirus among animals (12), especially in
the Rhinolophus bat family (86). Chinese bats have
high commercial value, since they are used in
07:24 (Ml 0" •

Cases continued to increase

exponentially and modelling studies
reported an epidemic doubling time of
1.8 d [10]. In fact on the 12th of
February, China changed its definition
of confirmed cases to include patients
with negative/ pending molecular tests
but with clinical, radiologic and
epidemiologic features of COVID-19
leading to an increase in cases by
15,000 in a single day [6]. As of
05/03/2020 96,000 cases worldwide
(80,000 in China) and 87 other
countries and 1international
conveyance (696, in the cruise ship
Diamond Princess pa rked off the
coast of Japan) have been reported
[2]. It is important to note that while
the number of new cases has reduced
in China lately, they have increased
exponentially in other countries
including South Korea, Italy and Iran.
Of those infected, 20°/o are in critical

• •
07:24 (Ml 0 '\ • •..id i
ex1enaea IO 01ner c1i1es or ttun e1
province. Cases of COVID-19 in
countries outside China were reported
in those with no history of travel to
China suggesting that local human-to
human transmission was occurring in
these countries [9]. Airports in
different countries including India put
in screening mechanisms to detect
symptomatic people returning from
China and placed them in isolation and
testing them for COVID-19. Soon it was
apparent that the inf ection could be
transmitted from asymptomatic people
and also before onset of symptoms.
Therefore, countries including India
who evacuated their citizens from
Wuhan through special flights or had
travellers returning from China, placed
all people symptomatic or otherwise in
isolation for 14 d and tested them for
the virus.

Cases continued to increase

exponentially and modelling studies

• •
07:23 (Ml 0" •
had >95°/o homology with the bat
coronavirus and > 70°/o similarity with
the SARS- CoV. Environmental samples
from the Huanan sea food market also
tested positive, signifying that the
virus originated from there [7]. The
number of cases started increasing
exponentially, some of which did not
have exposure to the live animal
market, suggestive of the fact that
human-to-human transmission was
occurring [8]. The first fatal case was
reported on 11th Jan 2020. The
massive migration of Chinese during
the Chinese New Year fuelled the
epidemic. Cases in other provinces of
China,
other countries (Thailand, Japan and
South Korea in quick succession) were
reported in people who were returning
from Wuhan. Transmission to
healthca re workers caring for patients
was described on 20th Jan, 2020. By
23rd January, the 11million population
of Wuhan was placed under lock down
• •
07:27 (Ml 0" •
.I.

been used based on the experience

·
with SARS and MERS. In a historical
control study in patients with SARS,
patients treated with lopinavir
ritonavir with ribavirin had better
outcomes as compared to those given
ribavirin alone [15].

In the case series of 99 hospitalized

patients with COVID-19 infection from
Wuhan, oxygen was given to 76°/o, non
invasive ventilation in 13°/o,
mecha nical ventilation in 4°/o,
extracorporeal membrane oxygenation
(ECMO) in 3°/o, continuous renal
replacement therapy (CRRT) in 9°/o,
antibiotics in 71°/o, antifungals in
15°/o, glucocorticoids in 19°/o and
intravenous immunoglobulin therapy in
27°/o [15].
Antiviral therapy consisting of
oseltamivir, ganciclovir and lopinavir
ritonavir was given to 75°/o of the
patients. The duration of non-invasive
ventilation was 4-22 d [median 9 d]
• •
another study, the average reproductive number of
COVID-19 was found to be 3.28, which is
significantly higher than the initial WHO estimate of
1.4 to 2.5 (77). It is too early to obtain the exact R0
value, since there is a possibility of bias due to
insufficient data. The higher Ro value is indicative of
the more significant potential of SARS-CoV-2
transmission in a susceptible population. This is not
the first time where the culinary practices of China
have been blamed for the origin of novel coronavirus
infection in humans. Previously, the animals present
in the live-animal market were identified to be the
intermediate hosts of the SARS outbreak in China
(78). Several wildlife species were found to harbor
potentially evolving coronavirus strains that can
overcome the species barrier (79). One of the main
principles of Chinese food culture is that live
slaughtered animals are considered more nutritious
(5).
After 4 months of struggle that lasted from
December 2019 to March 2020, the COVID-19
situation now seems under control in China. The wet
animal markets have reopened, and people have
started buying bats, dogs, cats, birds , scorpions,
badgers, rabbits, pangolins (scaly anteaters), minks ,
soup from palm civet, ostriches, hamsters, snapping
turtles, ducks, fish, Siamese crocodiles, and other
other clinical trials in different phases are still
ongoing elsewhere.

Immunomod ulatory agents. SARS- CoV-2 triggers

a strong immun e response which m ay cause
cytokin e storm
' syndrome 60 61 • Thus,
immunomodulatory agents that inhibit the excessive
inflammatory response may be a poten tial adju
n ctive therapy for COV ID -19. Dexamethasone
is a corticosteroid often used in a wide range of
conditions to relieve inflammation through its anti-
inflammatory and immunosuppressant effects.
Recently, the RECOVERY trial found
dexamethasone reduced mortality by about one third
in hospitalized patients with COVID-19who received
invasive mechan ical ventilation and by one fifth in
patients receiving oxygen. By • contrast, no benefit
was found in patients without respiratory support 146
Tocilizumab and sarilumab,two types of interleukin -
6
(IL-6) receptor-specific antibodies previously used to
treat various types of arthritis, including rheumatoid
arthritis, and cytokine release syndrome, showed
effec tiveness in the treatment of severe COVID-19
by atten uating the cytokine storm in a small
uncontrolled trial147• B evacizumab is an anti-vascular
endothelial growth factor (VEGF) medication that
could potentially reduce pulmonary oedema in
patients with severe COVID-19. Eculizum ab is a
specific m onoclon al antibody that inhibits the
proinflammatory complement protein CS.
Preliminary results showed that it induced a drop of
inflammatory m arkers and C-reactive protein levels,
suggesting its potential to be an option for the
treatment
of severe COVID-19 (REF. 148) .
proteins without the presence of S protein would not
confer any noticeable protection, with the absence of
detectable serum SARS-CoV-neutralizing antibodies
(170). Antigenic determinant sites present over S and
N structural proteins of SARS-CoV-2 can be
explored as suitable vaccine candidates (294). In the
Asian population, S, E, M, and N proteins of SARS
CoV-2 are being targeted for developing subunit
vaccines against COVID-19 (295).
The identification of the immunodominant region
among the subunits and domains of S protein is
critical for developing an effective vaccine against
the coronavirus. The C-terminal domain of the Sl
subunit is considered the immunodominant region of
the porcine deltacoronavirus S protein (171).
Similarly, further investigations are needed to
determine the immunodominant regions of SARS
CoV-2 for facilitating vaccine development.
However, our previous attempts to develop a
universal vaccine that is effective for both SARS
CoV and MERS-CoV based on T-cell epitope
similarity pointed out the possibility of cross
reactivity among coronaviruses (172). That can be
made possible by selected potential vaccine targets
that are common to both viruses. SARS-CoV-2 has
been reported to be closely related to SARS-CoV
(173, 174). Hence, knowledge and understanding of
considerable protection in mice against a MERS CoV
lethal challenge. Such antibodies may play a crucial
role in enhancing protective humoral responses
against the emerging CoVs by aiming appropriate
epitopes and functions of the S protein. The cross-
neutralization ability of SARS-CoV RED specific
neutralizing MAbs considerably relies on the
resemblance between their REDs; therefore , SARS-
CoV RED-specific antibodies could cross
neutralized SL CoVs, i.e., bat-SL-CoV strain WIV l
(RBD with eight amino acid differences from SARS
CoV) but not bat-SL-Co V strain SHCO 14 (24
amino acid differences) (200).
Appropriate RED-specific MAbs can be
recognized by a relative analysis of RED of SARS
CoV-2 to that of SARS-CoV, and cross-neutralizing
SARS-CoV RED-specific MAbs could be explored
for their effectiveness against COVID-19 and further
need to be assessed clinically. The U.S.
biotechnology company Regeneron is attempting to
recognize potent and specific MAbs to combat
COVID-19. An ideal therapeutic option suggested
for SARS-CoV-2 (COVID-19) is the combination
therapy comprised of MAbs and the drug remdesivir
(COVID-19) (201). The SARS-CoV-specific human
MAb CR3022 is found to bind with SARS-CoV-2
RED, indicating its potential as a therapeutic agent
07:29 (Ml 0.
• All clinicians should keep ·
themselves updated about recent
developments including global
spread of the disease.

• Non-essential international travel

should be avoided at this time.

• People should stop spreading

myths and false information about
the disease and try to allay panic
and anxiety of the public.

Conclusions
This new virus outbreak has
challenged the economic, medical
and public health infrastructure of
China and to some extent, of other
countries especially, its neighbours.
Time alone will tell how the virus
will impact our lives here in India.
More so, future outbreaks of viruses
and pathogens of zoonotic origin are
likely to continue.
Therefore, apart from curbing this
outbreak_ efforts sh oul d be m a d e to
• •
07:28 (Ml 0" •

category A agents (cholera, plague).

Patients should be placed in separate
rooms or cohorted together. Negative
pressure rooms are not generally
needed. The rooms and surfaces and
equipment should undergo regular
decontamination preferably with
sodium hypochlorite. Healthcare
workers should be provided with fit
tested N95 respirators and protective
suits and goggles. Airborne
transmission precautions should be
taken during aerosol generating
procedures such as intubation, suction
and tracheostomies. All contacts
including healthcare workers should
be monitored for development of
symptoms of COVID-19. Patients can
be discharged from isolation once
they are afebrile for atleast 3 d and
have two consecutive negative
molecular tests at 1d sampling
interval. This recommendation is
diff erent from pandemic flu where
patients were
• •