and preventive strategies, including vaccines, immunotherapeutics, and antiviral drugs, have been

exploited against the previous CoV outbreaks (SARS-CoV and MERS-CoV) (8, 104, 164-167). These
valuable options have already been evaluated for their potency, efficacy, and safety, along with several
other types of current research that will fuel our search for ideal therapeutic agents against COVID-19
(7, 9, 19, 21, 36). The primary cause of the unavailability of approved and commercial vaccines, drugs,
and therapeutics to counter the earlier SARS-CoV and MERS-CoV seems to owe to the lesser attention
of the biomedicine and pharmaceutical companies, as these two CoVs did not cause much havoc,
global threat, and panic like those posed by the SARS-CoV-2 pandemic (19). Moreover, for such
outbreak situations, the requirement for vaccines and therapeutics/drugs exists only for a limited
period, until the outbreak is controlled. The proportion of the human population infected with SARS-
CoV and MERS-CoV was also much lower across the globe, failing to attract drug and vaccine
manufacturers and producers. Therefore, by the time an effective drug or vaccine is designed against
such disease outbreaks, the virus would have been controlled by adopting appropriate and strict
SplitsTree phylogeny analysis.

In the unrooted phylogenetic tree of different betacoronaviruses based on the S protein, virus sequences
from different subgenera grouped into separate clusters. SARS-CoV-2 sequences from Wuhan and
other countries exhibited a close relationship and appeared in a single cluster (Fig. 1). The CoVs from
the subgenus Sarbecovirus appeared jointly in SplitsTree and divided into three subclusters, namely,
SARS-CoV-2, bat-SARS-like-CoV (bat-SL-CoV), and SARS-CoV (Fig. 1). In the case of other
subgenera, like Merbecovirus, all of the sequences grouped in a single cluster, whereas in
Embecovirus, different species, comprised of canine respiratory CoVs, bovine CoVs, equine CoVs, and
human CoV strain (OC43), grouped in a common cluster. Isolates in the subgenera Nobecovorus and
Hibecovirus were found to be placed separately away from other reported SARS-CoVs but shared a bat
origin.

CURRENT WORLDWIDE SCENARIO OF SARS-CoV-2

This novel virus, SARS-CoV-2, comes under the subgenus Sarbecovirus of the Orthocorona virinae
subfamily and is entirely different from the viruses
exponentially in other countriesincluding South Korea, Italy and Iran. Of those infected, 20% are in
critical condition, 25% have recovered, and 3310 (3013 in China and 297 in othercountries) have died
[2]. India, which had reported only 3 cases till 2/3/2020, has also seen a sudden spurt in cases. By
5/3/2020, 29 cases had been reported; mostly in Delhi, Jaipur and Agra in Italian tourists and their
contacts. One case was reported in an Indian who traveled back from Vienna and exposed a large
number of school children in a birthday party at a city hotel. Many of the contacts of these cases have
been quarantined. These numbers are possibly an underestimate of the infected and dead due to
limitations of surveillance and testing. Though the SARS-CoV-2 originated from bats, the intermediary
mask and practice cough hygiene. Caregivers should be asked to wear a surgical mask when in the
same room as patient and use hand hygiene every 15-20 min.

The greatest risk in COVID-19 is transmission to healthcare workers. In the SARS outbreak of 2002,
21% of those affected were healthcare workers [31]. Till date, almost 1500 healthcare workers in China
have been infected with 6 deaths. The doctor who first warned about the virus has died too. It is
important to protect healthcare workers to ensure continuity of care and to prevent transmission of
infection to other patients. While COVID-19 transmits as a droplet pathogen and is placed in Category
B of infectious agents (highly pathogenic H5N1 and SARS), by the China National Health
Commission, infection control measures recommended are those for
strain of Mycobacterium bovis. At present, three new clinical trials have been registered to evaluate the
protective role of BCG vaccination against SARS-CoV-2 (363). Recently, a cohort study was
conducted to evaluate the impact of childhood BCG vaccination in COVID-19 PCR positivity rates.
However, childhood BCG vaccination was found to be associated with a rate of COVID-19-positive
test results similar to that of the nonvaccinated group (364). Further studies are required to analyze
whether BCG vaccination in childhood can induce protective effects against COVID-19 in adulthood.
Population genetic studies conducted on 103 genomes identified that the SARS-CoV-2 virus has
evolved into two major types, L and S. Among the two types, L type is expected to be the most
prevalent (~70%), followed by the S type (~30%) (366). This finding has a significant impact on our
race to develop an ideal vaccine, since the vaccine candidate has to target both strains to be considered
effective. At present, the genetic differences between the L and S types are very small and may not
affect the immune response. However, we can expect further genetic variations in the coming days that
could lead to the emergence of new strains (367).
pandemic flu where patients were asked to resume work/school once afebrile for 24 h or by day 7 of
illness. Negative molecular tests were not a prerequisite for discharge.

At the community level, people should be asked to avoid crowded areas and postpone non-essential
travel to places with ongoing transmission. They should be asked to practice cough hygiene by
coughing in sleeve/ tissue rather than hands and practice hand hygiene frequently every 15-20 min.
Patients with respiratory symptoms should be asked to use surgical masks. The use of mask by healthy
people in public places has not shown to protect against respiratory viral infections and is currently not
recommended by
WHO. However, in China, the public has been asked to wear masks in public and especially in
crowded places and large scale gatherings are prohibited (entertainment parks etc). China is also
(entertainment parks etc). China is also considering introducing legislation to prohibit selling and
trading of wild animals [32].

The international response has been dramatic. Initially, there were massive travel restrictions to China
and people returning from China/ evacuated from China are being evaluated for clinical symptoms,
isolated and tested for COVID-19 for 2 wks even if asymptomatic. However, now with rapid world
wide spread of the virus these travel restrictions have extended to other countries. Whether these efforts
will lead to slowing of viral spread is not known.

A candidate vaccine is under development.

Practice Points from an Indian Perspective

arucle gives a bird's eye view apout this new virus. Since knowledge about this virus is rapidly
evolving, readers are urged to update themselves regularly.

History

Coronaviruses are enveloped positive sense RNA viruses ranging from 60 nm to 140 nm in diameter
with spike like projections on its surface giving it a crown like appearance under the electron
microscope; hence the name coronavirus [3]. Four corona viruses namely HKU1, NL63, 229E and
OC43 have been in circulation in humans, and generally cause mild respiratory disease.

There have been two events in the past two decades wherein crossover of animal betacorona viruses to
humans has resulted in severe disease. The first such instance was in 2002-2003 when a
lower respiratory tracts. Acute viral interstitial pneumonia and humoral and cellular immune responses
were observed”. Moreover, prolonged virus shedding peaked early in the course of infection in
asymptomatic macaques’, and old monkeys showed severer interstitial pneumonia than young
monkeys’, which is similar to what is seen in patients with COVID-19. In human ACE2-transgenic
mice infected with SARS-CoV-2, typical interstitial pneumonia was present, and viral antigens were
observed mainly in the bronchial epithelial cells, macrophages and alveolar epithelia. Some human
ACE2-transgenic mice even died after infection". In wide-type mice, a SARS-CoV-2 mouse-adapted
strain with the N501Y alteration in the RBD of the S protein was generated at passage 6. Interstitial
pneumonia and inflammatory responses were found in both young and aged mice after infection with
the mouse-adapted strain”. Golden hamsters also showed typical symptoms after being infected with
SARS-CoV-2 (REF”). In other animal models, including cats and ferrets, SARS-CoV-2 could
efficiently replicate in the upper respiratory tract but did not induce severe clinical symptoms*>™. As
transmission by direct contact and air was observed in infected ferrets and hamsters, these animals
could be used to model different transmission modes of COVID-19 (REFS). Animal models offer
important information for understanding the pathogenesis of SARS-CoV-2 infection and the
transmission dynamics of SARS CoV-2, and are important to evaluate the efficacy of antiviral
therapeutics and vaccines.

Clinical and epidemiological features

It appears that all ages of the population are susceptible to SARS-CoV-2 infection, and the median age
of infection is around 50 years” “>, However, clinical manifestations differ with age. In general, older
men (>60 year old) with co-morbidities are more likely to develop severe respiratory disease that
requires hospitalization
exponentially in other countries including South Korea, Italy and Iran. Of those infected, 20% are in
critical condition, 25% have recovered, and 3310 (3013 in China and 297 in other countries) have died
[2]. India, which had reported only 3 cases till 2/3/2020, has also seen a sudden spurt in cases. By
5/3/2020, 29 cases had been reported; mostly in Delhi, Jaipur and Agra in Italian tourists and their
contacts. One case was reported in an Indian who traveled back from Vienna and exposed a large
number of school children in a birthday party at a city hotel. Many of the contacts of these cases have
been quarantined.

These numbers are possibly an underestimate of the infected and dead due to limitations of surveillance
and testing. Though the SARS-CoV-2 originated from bats, the intermediary