Image 150

6.1 Laboratory testing for coronavirus disease 2019 (COVID-19) in suspected

human cases
The assessment of the patients with COVID-19 should be based on the clinical features and also epidemiological
factors. The screening protocols must be prepared and followed per the native context.3 Collecting and testing of
specimen samples from the suspected individual is considered to be one of the main principles for controlling and
managing the outbreak of the disease in a country. The suspected cases must be screened thoroughly in order to
detect the virus with the help of nucleic acid amplification tests such as reverse transcription polymerase chain
reaction (RTPCR). If a country or a particular region does not have the facility to test the specimens, the specimens
of the suspected individual should be sent to the nearest reference laboratories per the list provided by WHO.32 It is
also recommended that the suspected patients be tested for the other respiratory pathogens by performing the routine
laboratory investigation per the Iocal guidelines, mainly to differentiate from other viruses that include influenza
virus, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human
Image 151
mice, and hDPP4-Tg mice (transgenic for expressing hDPP4) for MERS-CoV infection (221). The CRISPR-Cas9
gene-editing tool has been used for inserting genomic alterations in mice, making them susceptible to MERS-CoV
infection (222). Efforts are under way to recognize suitable animal models for SARS-CoV2/COVID-19, identify the
receptor affinity of this virus, study pathology in experimental animal models, and explore virus-specific immune
responses and protection studies, which together would increase the pace of efforts being made for developing
potent vaccines and drugs to counter this emerging virus. Cell lines, such as monkey epithelial cell lines (LLC-MK2
and Vero-B4), goat lung cells, alpaca kidney cells, dromedary umbilical cord cells, three-dimensional advanced and
vivo extracheobronchial tissue, have been explored to study human CoVs (MERS-CoV) (223, 224). Vero and Huh-7
cells (human liver cancer cells) have been used for isolating SARS-CoV-2 (194).
Recently, an experimental study with rhesus monkeys as animal models revealed the absence of any viral loads in
nasopharyngeal and anal swabs, and no viral replication was recorded in the primary tissues at a time interval of 5
days post-reinfection in re-exposed monkeys (274). The subsequent pathological radiological, virological, and
Image 152
of plasma cytokines, which suggests an inmmunopatho-logical process caused by a cytokine storm 60,86,87, In this
cohort of patient, around 2.3% people died within a median time of 16 days from disease onset8, Men older than 68
years had a higher risk of respiratory fail-ure, acute cardiac injury and heart failure that led to death, regardless of a
history of cardiovascular disease (FIG. 4). Most patients recovered enough to be released from hospital in 2
weeks9,80 (FIG. 4). Early transmission of SARS-CoV-2 in Wuhan in December 2019 was initially linked to the
Huanan Seafood Wholesale Market, and it was suggested as the source of the outbreak 9,22,60 . However, community
transmission might have happened before that88. Later, ongoing human-to-human transmission propagated the
outbreak'. It is generally accepted that SARS-CoV-2 is more transmissible than SARS-CoV and MERS-CoV;
however, determination of an accurate reproduction number (RO) for COVID-19 is not possible yet, as many
asymptomatic infections cannot be accurately accounted for at this stage 89. An estimated R0 of 2.5 (ranging from 1.8
to 3.6) has been proposed for SARS-CoV-2 recently, compared with 2.0-3.0 for SARS-CoV 90. Notably, most of the
SARS-CoV-2 human-to-human transmission early in China occurred in family clusters, and in other countries large
outbreaks also happened in other settings, such as migrant worker communities, slaughter-houses and meat packing
plants, indicating the necessity of isolating infected people 9,12,91-93. Nosocomial transmission was not the main source
of transmission in China because of the implementation of infection control measures in clinical settings 9. By
contrast, a high risk of nosocomial transmission was reported in some other
Image 153
particularly in bats. both in vitro and in Vivo studies (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.
Image 154
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 18]. 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 healthcare workers caring for
patients was described on 20th Jan, 2020. By 23rd January, the 11 million population of Wuhan was placed under
lock down with restrictions of entry and exit from the region. Soon this lock down was
Image 155
nsps and Accessory Proteins Besides the important structural proteins, the SARS-CoV-2 genome contains 15 nsps,
nsp1 to nsp10 and nsp12 to nsp16, and 8 accessory proteins (3a, 3b, p6, 7a, 7b, 8b, 9b, and ORF14) (16). All these
proteins play a specific role in viral replication (27). Unlike the accessory proteins of SARS-CoV, SARS-CoV-2
does not contain 8a protein and has a longer 8b and shorter 3b protein (16). The nsp7, nsp13, envelope, matrix, and
p6 and 8b accessory proteins have not been detected with any amino acid substitutions compared to the sequences of
other coronaviruses (16).
The virus structure of SARS-CoV-2 is depicted in
Fig. 2. Spike glycoprotein S required for the entry of the infectious virion particie Membrane protein (M) (most
abundant viral protein Major structural protein Envelope glycoprotein (E) (smallest among the major structural
poteins Nucleocapsid protein (N +Single-stranded positive Sense HiNA genome Lipid bilayer FIG 2 SARS-CoV-2
virus structure.
Image 156
developed for rapid and colorimetric detection of this virus (354). RT-LAMP serves as a simple, rapid, and sensitive
diagnostic method that does not require sophisticated equipment or skilled personnel (349). An interactive web-
based dashboard for tracking SARS-CoV-2 in a real-time mode has been designed (238). A smartphone-integrated
home-based point-of-care testing (POCT) tool, a paper-based POCT combined with LAMP, is a useful point-of-care
diagnostic (353). An Abbott ID Now COVID-19 molecular POCT-based test, using isothermal nucleic acid
amplification technology, has been designed as a point-of-care test for very rapid detection of SARS-CoV-2 in just 5
min (344). A CRISPR-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) diagnostic for
rapid detection of SARS-CoV-2 without the requirement of specialized instrumentation has been reported to be very
useful in the clinical diagnosis of COVID-19 (360). A CRISPR-Cas12-based lateral flow assay also has been
developed for rapid detection of SARS-CoV-2 (346). Artificial intelligence, by means of a three dimensional deep-
learning model, has been developed for sensitive and specific diagnosis of COVID-19 via CT images (332).
Tracking and mapping of the rising incidence rates, disease outbreaks, community spread,
Image 157

Splits Tree 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 Orthocoronavirinae subfamily and is
entirely different from the viruses
Image 158
might be lower. Further genetic analysis is required between SARS-CoV-2 and different strains of SARS-CoV and
SARS-like (SL) CoVs to evaluate the possibility of repurposed vaccines against COVID-19. This strategy will be
helpful in the scenario of an outbreak, since much time can be saved, because preliminary evaluation, including in
vitro studies, already would be completed for such vaccine candidates. Multiepitope subunit vaccines can be
considered a promising preventive strategy against the ongoing COVID-19 pandemic. n silico and advanced
immunoinformatic tools can be used to develop multiepitope subunit vaccines. The vaccines that are engineered by
this technique can be further evaluated using docking studies and, if found effective, then can be further evaluated in
animal models (365). identifying epitopes that have the potential to become a vaccine candidate is critical to
developing an effective vaccine against COVID-19. The immunoinformatics approach has been used for
recognizing essential epitopes of cytotoxic T lymphocytes and B cells from the surface glycoprotein of SARS-CoV-
2. Recently, a few epitopes have been recognized from the SARS-C%V-2 surface glycoprotein. The selected
epitopes explored targeting molecular dynamic simulations,
Image 159
Inhibition of virus replication. Replication inhibitors include remdesivir (GS-5734), favipiravir (T-705), ribavirin,
lopinavir and ritonavir. Except for lopinavir and ritonavir, which inhibit 3CLpro, the other three all target RdRp2815
(FIG. 5). Remdesivir has shown activity against SARS-CoV-2 in vitro and in vivo 28156, A clinical study revealed a
lower need for oxygen support in patients with COVID-19 (REF37). Preliminary results of the Adaptive COVID-19
Treatment Trial (ACTT) clinical trial by the National Institute of Allergy and Infectious Diseases (NIAID) reported
that remdesivir can shorten the recovery time in hospitalized adults with COVID-19 by a couple days compared with
placebo, but the difference in mortality was not statistically significantly, The FDA has issued an emergency use
authorization for remdesivir for the treatment of hospitalized patients with severe COVID-19. It is also the first
approved option by the European Union for treatment of adults and adolescents with pneumonia requiring
supplemental oxygen. Several international phase II clinical trials are continuing to evaluate the safety and efficacy
of remdesivir for the treatment of COVID-19. Favipiravir (T-705), which is an antiviral drug developed in Japan to
treat influenza, has been approved in China, Russia and India for the treatment of COVID-19. A clinical study in
China showed that favipiravir significantly reduced the signs of improved disease signs on chest imaging and
shortened the time to viral clearance. A preliminary report in Japan showed rates of clinical improvement of 73.8%
and 87.8% from the start of favipiravir therapy in patients with mild COVID-19 at 7 and 14 days, respectively, and
40.1% and 60.3% in patients with severe COVID-19 at 7 and 14 days,
Image 160
there, there is an increase in the outbreak of this virus through human-to-human transmission, with the fact that it
has become widespread around the globe. This confirms the fact similar to the previous epidemics, including SARS
and MERS, that this coronavirus exhibited potential human-to-human transmission, as it was recently declared a
pandemic by WHO.26 Respiratory droplets are the major carrier for coronavirus transmission. Such droplets can
either stay in the nose or mouth or enter the lungs via the inhaled air. Currently, it is known that COVID-19's
transmission from one person to another also occurs through touching either an infected surface or even an object.
With the current scant awareness of the transmission systems however, airborne safety measures with a high-risk
procedure have been proposed in many countries. Transmission levels, or the rates from one person to another,
reported differ by both location and interaction with involvement in infection control. It is stated that even
asymptomatic individuals or those individuals in their incubation period can act as carrier of SARS-CoV2.27, 28
With the data and evidence provided by the CDC, the usual incubation period is probably 3 to 7 days, sometimes
being prolonged up to even 2 weeks, and the typical symptom occurrence
Image 161
themselves while examining such patients and practice hand hygiene frequently. Suspected cases should be referred
to government designated centres for isolation and testing (in Mumbai, at this time, it is Kasturba hospital).
Commercial kits for testing are not yet available in India. Patients admitted with severe pneumonia and acute
respiratory distress syndrome should be evaluated for travel history and placed under contact and droplet isolation.
Regular decontamination of surfaces should be done. They should be tested for etiology using multiplex PCR panels
if logistics permit and if no pathogen is identified, refer the samples for testing for SARS-CoV-2.
Image 162
Respectively140, However, this study did not include a control arm, and most of the trials of favilavir were based on a
small sample size. For more reliable assessment of the effectiveness of favilavir for treating COVID-19, large-scale
randomized controlled trials should be conducted. Lopinavir and ritonavir were reported to have in vitro inhibitory
activity against SARS-CoV and MERS-CoVL, Alone, the combination of lopinavir
Image 163
Virological, radiological, and pathological observations indicated that the monkeys with reexposure had no
recurrence of cOVID-19, like the SARS-CoV-2-infected monkeys without rechallenge. These findings suggest that
primary infection with SARS-CoV-2 could protect from later exposures to Virological, radiological, and the virus,
which could help in defining disease prognosis and crucial inferences for designing and developing potent vaccines
against COVID-19 (274).

PREVENTION, CONTROL, AND MANAGEMENT

In contrast to their response to the 2002 SARS outbreak, China has shown immense political openness in reporting
the COVID-19 outbreak promptly. They have also performed rapid sequencing of COVID-19 at multiple levels and
shared the findings globally within days of identifying the novel virus (225). The move made by China opened a
new chapter in global health security and diplomacy. Even though complete lockdown was declared following the
COVID-19 outbreak in Wuhan, the large-scale movement of people has resulted in a radiating spread of infections
in the surrounding provinces as well as to several other countries. Large-scale screening programs might
Image 164

13 CONVALESCENT PLASMA THERAPYY

Guo Yanhong, an official with the National Health Commission (NHC), stated that convalescent plasma therapy isa
significant method for treating severe COVID-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 1 st and 9th February 2020 from a severely ill patient who was given treatment at
a hospital in Jiangxia 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.
Image 165
had 95% homology with the bat coronavirus and> 70% 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 healthcare workers caring for patients was described on 20th Jan, 2020. By
23rd January, the 11 million population of Wuhan was placed under lock down
Image 166
snakes, and various other wild animals (20, 30, 79, 93, 124, 125, 287). Coronavirus infection is linked to different
kinds of clinical manifestations, varying from enteritis in cows and pigs, upper respiratory disease in chickens, and
fatal respiratory infections in humans (30).
Among the CoV genera, Alphacoronavirus and while infect mammals, Betacoronavirus Gammacoronavirus and
Deltacoronavirus mainly infect birds, fishes, and, sometimes, mammals (27, 29, 106). Several novel coronaviruses
that come under the genus Deltacoronavirus have been discovered in the past from birds, like Wigeon coronavirus
HKU20, Bulbul coronavirus HKU11, Munia coronavirus HKU13, white-eye coronavirus HKU16, night-heron
coronavirus HKU19, and common moorhen coronavirus HKU21, as well as from pigs (porcine coronavirus HKUI5)
(6, 29). Transmissible gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine
hemagglutinating encephalomyelitis virus (PHEV) are some of the coronaviruses of swine. Among them, TGEV and
PEDV are responsible for causing severe gastroenteritis in young piglets with noteworthy morbidity and mortality.
Infection with PHEV also causes enteric infection but can cause encephalitis due to its ability to infect the nervous
Image 167
dogs have low susceptibility, While the Chickens, ducks, and pigs are not at all susceptible to SARS-CoV-2 (329).
Similarly, the National Veterinary Services Laboratories of the USDA have reported COVID-19 in tigers and lions
that exhibited respiratory signs like dry cough and wheezing. The zoo animals are suspected to have been infected
by an asymptomatic zookeeper (335). The total number of COVID-19- positive cases in human beings is increasing
at a high rate, thereby creating ideal conditions for viral spillover to other species, such as pigs. The evidence
obtained from SARS-CoV suggests that pigs can get infected with SARS-CoV-2 336). However, experimental
inoculation with SARS-CoV-2 failed to infect pigs (329).
Further studies are required to identify the possible animal reservoirs of SARS-CoV-2 and the seasonal variation in
the circulation of these viruses in the animal population. Research collaboration between human and animal health
sectors is becoming a necessity to evaluate and identify the possible risk factors of transmission between animals
and humans. Such cooperation will help to devise efficient strategies for the management of emerging zoonotic
diseases (12).
Image 168
prevent further spread of disease at mass gatherings, functions remain canceled in the affected cities, and persons are
asked to work from home (232). Hence, it is a relief that the current outbreak of COVID-19 infection can be brought
under control with the adoption of strategic preventive and control measures along with the early isolation of
subsequent cases in the coming days. Studies also report that since air traffic between China and African countries
increased many times over in the decade after the SARS outbreak, African countries need to be vigilant to prevent
the spread of novel coronavirus in Africa (225). Due to fear of virus spread, Wuhan City was completely shut down
(233). The immediate control of the ongoing COVID-19 outbreaks appears a mammoth task, especially for
developing countries, due to their inability to allocate quarantine stations that could screen infected individuals'
movements (234). Such underdeveloped countries should divert their resources and energy to enforcing the primary
level of preventive measures, like controlling the entry of individuals from China or countries where the disease has
flared up, isolating the infected individuals, and quarantining individuals with suspected infection. Most of the sub-
Saharan African countries have a fragile health system that can be
Image 169

Abstract
There is a new public health crises threatening the world with the emergence and spread of 2019 novel coronavirus
(2019-nCoV) or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virus originated in bats
and was transmitted to humans through yet unknown intermediary animals in Wuhan, Hubei province, China in
December 2019. There have been around 96,000 reported cases of coronavirus disease 2019 (COVID-2019) and
3300 reported deaths to date (05/03/2020). The disease is transmitted by inhalation or contact with infected droplets
and the incubation period ranges from 2 to 14d. The symptoms are usually fever, cough, sore throat, breathlessness,
fatigue, malaise among others. The disease is mild in most people; in some (usually the elderly and those with
comorbidities may progress to
Image 170
respiratory infection (SARI) and respiratory distress, shock or hypoxaemia. Patients with SARI can be given
conservative fluid therapy only when there is no evidence of shock. Empiric antimicrobial therapy must be started to
manage SARI. For patients with sepsis, antimicrobials must be administered within 1 hour of initial assessments.
The WHO and CDC recommend that glucocorticoids not be used in patients with COVID-19 pneumonia except
where there are other indications (exacerbation of chronic obstructive pulmonary disease). 59
Patients' clinical deterioration is closely observed with SARI; however, rapidly progressive respiratory failure and
sepsis require immediate supportive care interventions comprising quick use of neuromuscular blockade and
sedatives, hemodynamic management, nutritional support, maintenance of blood glucose levels, prompt assessment
and treatment of nosocomial pneumonia, and prophylaxis against deep venous thrombosis (DVT) and
gastrointestinal (GI) bleeding.0 Generally, such patients give way to their primary illness to secondary
complications like sepsis or multi organ system failure 48.
Image 171
To assess the genetic variation of different SARS- CoV-2 strains, the 2019 Novel Coronavirus Resource of China
National Center for Bioinformation aligned 77,801 genome sequences of SARS-CoV-2 detected globally and
identified a total of 15,018 mutations, including 14,824 single-nucleotide polymorphisms (BIGD)S", In the S
protein, four amino acid alterations, V483A, L4551, F456V and G476S, are located near the binding interface in the
RBD, but their effects on binding to the host receptor are unknown. The alteration D614G in the S1 subunit was
found far more frequently than other S variant sites, and it is the marker of a major subclade of SARS-CoV-2 (clade
G). Since March 2020, SARS-CoV-2 variants with G614 in the S protein have replaced the original D614 variants
and become the dominant form circulating globally. Compared with the D614 variant, higher viral loads were found
in patients infected with the G614 variant, but clinical data suggested no significant link between the D614G
alteration and disease severity Pseudo typed viruses carrying the S protein with G614 generated higher infectious
titres than viruses carrying the S protein with D614, suggesting the alteration may have increased the infectivity of
SARS-CoV-2 (REF). However, the results of in vitro experiments based on pseudo virus models may not exactly
reflect natural infection. This preliminary finding should be validated by more studies using wild-type SARS-CoV-2
variants to infect different target cells and animal models. Whether this amino acid change enhanced virus
transmissibility is also to be determined. Another marker mutation for SARS-CoV-2 evolution is the single-
nucleotide
Image 172
specifically in the respiratory tract will help to reduce virus-triggered immune pathologies in COVID-19 (209). The
later stages of coronavirus-induced inflammatory cascades are characterized by the release of proinflammatory
interleukin-1 (IL-1) family members, such as IL-1 and IL-33. Hence, there exists a possibility that the inflammation
associated with coronavirus can be inhibited by utilizing anti-inflammatory cytokines that belong to the IL-I family
(92). It has also been suggested that the actin protein is the host factor that is involved in cell entry and pathogenesis
of SARS-CoV-2. Hence, those drugs that modulate the biological activity of this protein, like ibuprofen, might have
some therapeutic application in managing the disease (174). The plasma angiotensin 2 level was found to be
markedly elevated in COVID-19 infection and was correlated with viral load and lung injury. Hence, drugs that
block angiotensin receptors may have potential for treating COVID-19 infection (121). A scientist from Germany,
named Rolf Hilgenfeld, has been working on the identification of drugs for the treatment of coronaviral infection
since the time of the first SARS outbreak (19). The SARS-CoV $2 subunit has a significant function in mediating
virus fusion that provides entry into the host cell. Heptad repeat 1 (HRI) and heptad
Image 173
Population, the in vitro and in Vivo studies carried out on the isolated virus confirmed that there is a potential risk
for the reemergence of SARS-CoV infection from the viruses that are currently circulating in the bat population
(105).

CLINICAL PATHOLOGY OF SARS-CoV-2 (COVID-19)

The disease caused by SARS-CoV-2 is also named severe specific contagious pneumonia (SSCP), Wuhan
pneumonia, and, recently, COVID-19 (110). Compared to SARS-CoV, SARS-CoV-2 has less severe pathogenesis
but has superior transmission capability, as evidenced by the rapidly increasing number of COVID-19 cases (111).
The incubation period of SARS-CoV-2 in familial clusters was found to be 3 to 6 days (112). The mean incubation
period of COVID-19 was found to be 6.4 days, ranging from 2.1 to 11.1 days (113). Among an carly affected group
of 425 patients, 59 years was the median age, of which more males were affected (114). Similar to SARS and
MERS, the severity of this nCoV is high in age groups above 50 years (2, 115). Symptoms of COVID-19 include
fever, cough, myalgia or fatigue, and, less commonly, headache, hemoptysis, and diarrhea (116, 282). Compared to
the SARS-CoV-2-infected patients in Wuhan during
Image 174

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 ($7). 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 (IFN) and RNA interference (62). Compared to that
of SARS-CoV, the N protein of SARS-CoV-2 possess five amino acid mutations, where two are in the intrinsically
dispersed region (IDR; positions 25 and 26), one each in the NTD (position 103), LKR (position 217), and CTD
(position 334) (16).

nsps and Accessory Proteins

Image 175
high commercial value, Since they are used in traditional Chinese medicine (TCM). Therefore, the handling of bats
for trading purposes poses a considerable risk of transmitting zoonotic CoV epidemics (139).
Due to the possible role played by farm and wild animals in SARS-CoV-2 infection, the WHO, in their novel
coronavirus (COVID-19) situation report, recommended the avoidance of unprotected contact with both farm and
wild animals (25). The live-animal markets, like the one in Guangdong, China, provides a setting for animal
coronaviruses to amplify and to be transmitted to new hosts, like humans (78). Such markets can be considered a
critical place for the origin of novel zoonotic public health significance in the event of an outbreak. Bats are the
diseases and have enormous reservoirs for several viruses; hence, the role of bats in the present outbreak cannot be
ruled out (140). In a qualitative study conducted for evaluating the zoonotic risk factors among rural communities of
frequent human-animal southern China, the interactions along with the low environmental biosecurity were
identified as levels of significant risks for the emergence of zoonotic disease in local communities (141, 142). The
comprehensive sequence analysis of the
Image 176
Viruses in nasal washes, saliva, urine and faeces for up to 8 days after infection, and a few naive ferrets with only
indirect contact were positive for viral RNA, suggesting airborne transmission". In addition, transmission of the
virus through the ocular surface and prolonged presence of SARS-CoV-2 viral RNA in faecal samples were also
documented Coronaviruses can persist on inanimate surfaces for days, which could also be the case for SARS-CoV-
2 and could pose a prolonged risk of infection These findings explain the rapid geographic spread of CoVID-19, and
public health interventions to reduce transmission will provide benefit to mitigate the epidemic, as has proved
successful in China and several other countries, such as South KoreaoL10s

Diagnosis
Early diagnosis is crucial for controlling the spread of COVID-19. Molecular detection of SARS-CoV-2 nucleic acid
is the gold standard. Many viral nucleic acid detection kits targeting ORFib (including RdRp), N, E or S genes are
commercially available 0-10, The detection time ranges from several minutes to hours depending on the
technologyi0,10-11. The molecular detection can be affected by many factors. Although SARS-CoV-2 has been
detected from a variety of respiratory sources, including throat swabs, posterior oropharyngeal saliva,
nasopharyngeal swabs, sputum and bronchial fluid, the viral load is higher in lower respiratory tract samples123-1s,
In addition, viral nucleic acid was also found in samples from the intestinal tract or blood even when respiratory
samples were negatively, Lastly, viral load may already drop from its peak level on disease onset. Accordingly, false
negatives can be common when oral swabs and used, and so multiple detection methods should be adopted to
confirm a COVID-19 diagnosis7. Other detection methods were there-fore used to overcome this problem. Chest CT
was used to quickly identify a patient when the capacity of molecular detection was overloaded in Wuhan. Patients
Image 177
infections clinically or through routine lab tests. Therefore travel history becomes important. However, as the
epidemic spreads, the travel history will become irrelevant.

Treatment (21, 23]

Treatment is essentially supportive and symptomatic. The first step is to ensure adequate isolation (discussed later)
to prevent transmission to other contacts, patients and healthcare workers. Mild illness should be managed at home
with counseling about danger signs. The usual principles are maintaining hydration and nutrition and controlling
fever and cough. Routine use of antibiotics and antivirals such as oseltamivir should be avoided in confirmed cases.
In hypoxic patients, provision of oxygen through nasal prongs, face mask, high flow nasal
Image 178
Initially, the epicenter of the SARS-CoV-2 pandemic was China, which reported a significant number of deaths
associated with COVID-19, with 84,458 laboratory-confirmed cases and 4,644 deaths as of 13 May 2020 (Fig. 4).
As of 13 May 2020, SARS-CoV-2 confirmed cases have been reported in more than 210 countries apart from China
(Fig. 3 and 4) (WHO Situation Report 114) (25, 64). COVID-19 has been reported on all continents except
Antarctica. For many weeks, Italy was the focus of concerns regarding the large number of cases, with 221,216
cases and 30,911 deaths, but now, the United States is the country with the largest number of cases, 1,322,054, and
79,634 deaths. Now, the United Kingdom has even more cases (226,4671) and deaths (32,692) than Italy. A John
Hopkins University web platform has provided daily updates on the basic epidemiology of the COVID-19 outbreak
Image 179
in Yunnan. This novel bat virus, denoted 'RmYN02, is 93.3% identical to SARS-CoV-2 across the genome. In the
long lab gene, it exhibits 97.2% identity to SARS-CoV-2, which is even higher than for RaTG13 (REF). In addition
to RaTG13 and RmYN02, phylogenetic analysis shows that bat coronaviruses ZC45 and ZXC21 previously detected
in Rhinolophus pusillus bats from eastern China also fall into the SARS-CoV-2 lineage of the subgenus
Sarbecovirus* (FIG. 2). The discovery of diverse bat coronaviruses closely related to SARS-CoV-2 suggests that
bats are possible reservoirs of SARS-CoV-2 (REF). Nevertheless, on the basis of current findings, the divergence
between SARS-CoV-2 and related bat coronaviruses likely represents more than 20 years of sequence evolution,
suggesting that these bat coronaviruses can be regarded only as the likely evolutionary precursor of SARS-CoV-2
but not as the direct progenitor of SARS-CoV-2 (REF3"). Beyond bats, pangolins are another wildlife host probably
linked 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. These viruses from pangolins
independently seized by Guangxi and Guangdong provincial customs belong to two distinct sub lineages The
Guangdong strains, which were isolated or sequenced by different research groups from smuggled pangolins, have
99.8% sequence identity with each other. 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
Image 180

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 [91. 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 conference in Singapore
infected 11 other 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
Image 181
with COVID-19 showed typical features on initial CT, including bilateral multilobar ground-glass opacities with a
peripheral or posterior distributions, Thus, it has been suggested that CT scanning combined with repeated swab
tests should be used for individuals with high clinical suspicion of COVID-19 but who test negative in initial nucleic
acid screening. Finally, SARS-CoV-2 serological tests detecting antibodies to Nor S protein could complement
molecular diagnosis, particularly in late phases after disease onset or for retrospective studies16.120121. However,
the extent and duration of immune responses are still uncdear, and available serological tests differ in their
sensitivity and specificity, all of which need to be taken into account when one is deciding on serological tests and
interpreting their results or potentially in the future test for T cell responses.

Therapeutics
To date, there are no generally proven effective therapies for COVID-19 or antivirals against SARS-CoV-2,
although some treatments have shown some benefits in certain subpopulations of patients or for certain end points
(see later). Researchers and manufacturers are conducting large-scale clinical trials to evaluate various therapies for
COVID-19. As of 2 October 2020, there were about 405 therapeutic drugs in development for COVID-19, and
nearly 318 in human clinical trials (COVID-19 vaccine and therapeutics tracker). In the following sections, we
summarize potential therapeutics against SARS-CoV-2 on the basis of published clinical data and experience.
Image 182
adaptive evolution, close monitoring of the viral mutations that occur during subsequent human-to-human
transmission is warranted.

M Protein
The M protein is the most abundant viral protein present in the virion particle, giving a definite shape to the viral
envelope (48). It binds to the nucleocapsid and acts as a central organizer of coronavirus assembly (49). Coronavirus
M proteins are highly diverse in amino acid contents but maintain overall structural similarity within different
genera (50). The M protein has three transmembrane domains, flanked by a short amino terminus outside the virion
and a long carboxy terminus inside the virion (50). Overall, the viral scaffold is maintained by M-M interaction. Of
note, the M protein of SARS-CoV-2 does not have an amino acid substitution compared to that of SARS-CoV (16)

E Protein
The coronavirus E protein is the most enigmatic and smallest of the major structural proteins (51). It plays a
multifunctional role in the pathogenesis, assembly, and release of the virus (52). It is a small integral membrane
polypeptide that acts as a viroporin (ion channel) (53). The inactivation or
Image 183
the United States, tilorone dihydrochloride (tilorone), was previously found to possess potent antiviral activity
against MERS, Marburg, Ebola, and Chikungunya viruses (306). Even though it had broad-spectrum activity, it was
neglected for an extended period. Tilorone is another antiviral drug that might have activity against SARS-CoV-2.
Remdesivir, a novel nucleotide analog prodrug, was developed for treating Ebola virus disease (EVD), and it was
also found to inhibit the replication of SARS-CoV and MERS-CoV in primary human airway epithelial cell culture
systems (195). Recently, in vitro study has proven that remdesivir has better antiviral activity than lopinavir and
ritonavir. Further, in vivo studies conducted in mice also identified that treatment with remdesivir improved
pulmonary function and reduced viral loads and lung pathology both in prophylactic and therapeutic
lopinavir/ritonavir-IFN-y treatment in MERS-CoV infection 8). Remdesivir also inhibits a diverse range of
coronaviruses, including circulating human CoV, zoonotic bat CoV, and prepandemic zoonotic regimens compared
to CoV (195). Remdesivir is also considered the only significantly reduces therapeutic drug that pulmonary
pathology (8). All these findings indicate that remdesivir has to be further evaluated for its
Image 184
in asymptomatic patients. These abnormalities progress from the initial focal unilateral to diffuse bilateral ground-
glass opacities and will further progress to or coexist with lung consolidation changes within 1 to 3 weeks (159).
The role played by radiologists in the current scenario is very important. Radiologists can help in the early diagnosis
of lung abnormalities associated with COVID-19 pneumonia. They can also help in the evaluation of disease
severity, identifying its progression to acute respiratory distress syndrome and the presence of secondary bacterial
infections (160). Even though chest CT is considered an essential diagnostic tool for COVID-19, the extensive use
of CT for screening purposes in the suspected individuals might be associated with a disproportionate risk-benefit
ratio due to increased radiation exposure as well as increased risk of cross- infection. Hence, the use of CT for early
diagnosis of SARS-CoV-2 infection in high-risk groups should be done with great caution (292).
More recently, other advanced diagnostics have been designed and developed for the detection of SARS-CoV-2
(345, 347, 350-352). A reverse transcriptional amplification (RT-LAMP), namely, iLACO, has been developed for
rapid and colorimetric detection of this isothermal loop-mediated
Image 185
polymorphism at nucleotide position 28,144, which results in amino acid substitution of Ser for Lys at residue 84 of
the ORF8 protein. Those variants with this mutation make up a single subclade labelled as 'clade S334. Currently,
however, the available sequence data are not sufficient to interpret the early global transmission history ofthe virus,
and travel patterns, founder effects and public health measures also strongly influence the spread of particular
lineages, irrespective of potential biological differences between different virus variants.

Animal host and spillover

Bats are important natural hosts of alpha coronaviruses and beta coronaviruses. The closest relative to SARS-CoV-2
known to date is a bat coronavirus detected in Rhinolophus affinis from Yunnan province, China, named 'RaTG13,
whose full-length genome sequence is 96.2% identical to that of SARS-CoV-2 (REF"). This bat virus shares more
than 90% sequence identity with SARS-CoV-2 in all ORFs throughout the genome, including the highly variable S
and ORF8 (REF). Phylogenetic analysis confirms that SARS-CoV-2 dosely clusters with RaTG13 (FIG. 2). The
high genetic similarity between SARS-CoV-2 and RaTG13 supports the hypothesis that SARS-CoV-2 likely
originated from bats". Another related coronavirus has been reported more recently in a Rhinolophus malayanus bat
sampled in Yunnan. This novel bat virus denoted 'RmYN02'
Image 186
risk regions. It is derived from a live attenuated 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 non-vaccinated 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).
Image I87
and chest discomfort, and in severe cases dyspnea and bilateral lung infiltration". Among the first 27 documented
hospitalized patients, most cases were epidemiologically linked to Huanan Seafood Wholesale Market. a wet market
located in downtown Wuhan, which sells not only seafood but also live animals, including poultry and wildlife.
According to a retrospective study, the onset of the first known case dates back to 8 December 2019 (REF). On 31
December, Wuhan Municipal Health Commission notified the public of a pneumonia out-break of unidentified
cause and informed the World Health Organization (WHO" (FIG. I).
By metagenomic RNA sequencing and virus isolation from bronchoalveolar lavage fluid samples from patients with
severe pneumonia, independent team of Chinese scientists identified that the causative agent of this emerging
disease is a betacoronavirus that had never been seen befores.1011, On 9 January 2020, the result of this etiological
identification was publicly announced (FIG. 1). The first genome sequence of the novel coronavirus was published
on the Virological website on 10 January, and more nearly complete genome sequences determined by different
research institutes were then released via the GISAID database on 12 January Later, more patients with no history of
exposure to Huanan Seafood Wholesale Market were identified Several familial clusters of infection were reported,
and nosocomial infection also occurred in health-card facilities. All these cases provided clear evidence for human-
to-human transmission of the new virus- As the outbreak coincided with the approach of the lunar New Year, travel
between cities before the festival facilitated virus transmission in China. This novel coronavirus pneumonia soon
spread to other cities in Hubeivrovince and to other Darts of China. Within 1l month.
Image 188
vitro antiviral potential of FAD-approved drugs, viz., ribavirin, penciclovir, nitazoxanide, nafamostat, and
chloroquine, tested in comparison to remdesivir and favipiravir (broad-spectrum antiviral drugs) revealed remdesivir
and chloroquine to be highly effective against SARS-CoV-2 infection in vitro (194). Ribavirin, penciclovir, and
favipiravir might not possess noteworthy in vivo antiviral actions for SARS-CoV-2, since higher concentrations of
these nucleoside analogs are needed in vitro to lessen the viral infection. Both remdesivir and chloroquine are being
used in humans to treat other diseases, and such safer drugs can be explored for assessing their effectiveness in
COVID-19 patients.
Several therapeutic such agents, as chloroquine, lopinavir/ritonavir, hydroxychloroquine, have been proposed for
theclinical management of COVID-19 (299). A molecular docking study, conducted in the RNA- dependent RNA
polymerase (RdRp) of SARS-CoV-2 and commercially antipolymerase drugs, identified that drugs such as ribavirin,
remdesivir, galidesivir, tenofovir, and sofosbuvir bind RdRp tightly, indicating their vast available using different
potential to be used against COVID-19 (305). A broad-spectrum antiviral drug that was developed in the United
States, tilorone dihydrochloride (tilorone),
Image 189
understanding of the lung inflammation associated with this infection (24). SARS is a viral respiratory disease
caused by a formerly unrecognized animal CoV that originated from the wet markets in southern China after
adapting to the human host, thereby enabling transmission between humans (90). The SARS outbreak reported in
2002 to 2003 had 8,098 confirmed cases with 774 total deaths (9.6%) (93). The outbreak severely affected the Asia
Pacific region, especially mainland China (94). Even though the case fatality rate (CFR) of SARS-CoV-2 (COVID-
19) is lower than that of SARS-CoV, there exists a severe concern linked to this outbreak due to its epidemiological
similarity to influenza viruses (95, 279). This can fail the public health system, resulting in a pandemic (96).
MERS is another respiratory disease that was first reported in Saudi Arabia during the year 2012. The disease was
found to have a CFR of around 35% (97). The analysis of available data sets suggests that the incubation period of
SARS-CoV-2, SARS-CoV, and MERS-CoV is in almost the same range. The longest predicted incubation time of
SARS-CoV-2 is 14 days. Hence, suspected individuals are isolated for 14 days to avoid the risk of further spread
(98). Even though a high similarity has been reported
Image 190
respiratory syncytial virus, rhinovirus, human metapneumovirus and SARS coronavirus. It is advisable to
distinguish COVID-19 from other pneumonias such as mycoplasma pneumonia, chlamydia pneumonia and bacterial
pneumonia.35 Several published pieces of literature based on the novel coronavirus reported in China declared that
stool and blood samples can also collected from the suspected persons in order to detect the virus. However,
respiratory samples show better viability in identifying the virus, in comparison with the other specimens.34-36

6.2 Nucleic acid amplification tests (NAAT) for COVID-19 virus

The gold standard method of confirming the suspected cases of COVID-19 is carried out by detecting the unique
sequences of virus RNA through reverse transcription polymerase chain reaction (RT-PCR) along with nucleic acid
sequencing if needed. The various genes of virus identified so far include N, E, S (N: nucleocapsid protein, E:
envelope protein gene, S: spike protein gene) and RdRP genes (RNA-dependent RNA polymerase gene).32
Image 191
All of these therapeutic approaches have revealed both in vitro and in vivo anti-CoV potential. Although in vitro
research carried out with these therapeutics showed efficacy, most need appropriate support from randomized
animal or human trials. Therefore, they might be of limited applicability and require trials against SARS-CoV-2 to
gain practical usefulness. The binding of SARS-CoV-2 with ACE2 leads to the exacerbation of pneumonia as a
consequence of the imbalance in the renin- angiotensin system (RAS). The virus-induced pulmonary inflammatory
responses may be reduced by the administration of ACE inhibitors (ACEI) and angiotensin type-I receptor (ATIR)
(207).
Several investigations have suggested the use of small-molecule inhibitors for the potential control of SARS-COV
infections. Drugs of the FDA-approved compound library were screened to identify four inhibitors of MERS-CoV
small-molecule (chlorpromazine, chloroquine, loperamide, and lopinavir) that inhibited viral replication. These
compounds also hinder SARS-CoV and human CoVs (208). Therapeutic strategies involving the use of specific
antibodies or compounds that neutralize cytokines and their receptors will help to restrain the host inflammatory
responses. Such drugs acting specifically in the respiratory tract will help to
Image 192
severe illness, to minimise the risk of exposure to COVID-19 during outbreaks.33

9 VACCINES
The strange coronavirus outbreak in the Chinese city of Wuhan, now termed COVID-19, and its rapid transmission,
threatens people around the world. Because of its pandemic nature, the National Institutes of Health (NIH) and
pharmaceutical companies are involved in the development of COvID-19 vaccines. Xu Nanping, China's vice-
minister of science and technology, announced that the first vaccine is expected to be ready for clinical trials in
China at the end of April 2020.54 There is no approved vaccine and treatment for COVID-19 infections.
Vaccine development is sponsored and supported by the Biomedical Advanced Research and Development
Authority (BARDA), a component of the Office of the Assistant Secretary for Preparedness and Response (ASPR).
Sanofi will use its egg-free, recombinant DNA technology to produce an exact genetic match to proteins of the
virus.35
Image 193
major problem associated with diagnostic kit is that it works only when the test subject has an active infection,
limiting its use to the earlier stages of infection. Several laboratories around the world are currently developing
antibody-based diagnostic tests against SARS-CoV-2 (157).
Chest CT is an ideal diagnostic tool for identifying viral pneumonia. The sensitivity of chest CT is far superior to
that of X-ray screening. The chest CT findings associated with COVID-19-infected patients include characteristic
patchy infiltration that later progresses to ground-glass opacities (158). Early manifestations of COVID-
19pneumonia might not be evident in X-ray chest radiography. In such situations, a chest CT examination can be
performed, as it is considered highly specific for COVID-19 pneumonia (118).Those patients having COVID-19
pneumonia will exhibit the typical ground-glass opacity in their chest CT images (154). The patients infected
withCOVID-19 had elevated plasma angiotensin 2 levels. The level of angiotensin 2 was found to be linearly
associated with viral load and lung injury, indicating its potential as a diagnostic biomarker (121). The chest CT
imaging abnormalities associated withCOVID-19 pneumonia have also been observed even in asymptomatic
patients. These abnormalities
Image 194

Practice Points from an Indian Perspective

At the time of writing this article, the risk of coronavirus in India is extremely low. But that may change in the next
few weeks. Hence the following is recommended: Healthcare providers should take travel history of all patients with
respiratory symptoms, and any international travel in the past 2wks as well as contact with sick people who have
travelled internationally. They should set up a system of triage of patients with respiratory illness in the outpatient
department and give them a simple surgical mask to wear. They should use surgical masks themselves while
examining such
Image 195
of plasma cytokines, which suggests an immunopatho-logical process caused by a cytokine storm8, In this cohort of
patient, around 2.3% people died within a median time of 16 days from disease onset86, Men older than 68 years
had a higher risk of respiratory failure, acute cardiac injury and heart failure that led to death, regardless of a history
of cardiovascular disease"(FIG. 4). Most patients recovered enough to be released from hospital in 2 weeks** (FIG.
4).
Early transmission of SARS-CoV-2 in Wuhan in December 2019 was initially linked to the Huanan Seafood
Wholesale Market, and it was suggested as the source of the outbreak20. However, community transmission might
have happened before that". Later, ongoing human-to-human transmission propagated the outbreak'. It is generally
accepted that SARS-CoV-2 is more transmissible than SARS-CoV and MERS-CoV; however, determination of an
accurate reproduction number (R0) for COVID-19 is not possible yet, as many asymptomatic infections cannot be
accurately accounted for at this stage". An estimated R0 of 2.5 (ranging from1.8 to 3.6) has been proposed for
SARS-CoV-2 recently, compared with 2.0-3.0 for SARS-CoV". Notably, most of the SARS- CoV-2 human-to-
human transmission early in China occurred in family clusters, and in other countries large outbreaks also happened
in other set-tings, such as migrant worker communities, slaughterhouses and meat packing plants, indicating the
necessity of isolating infected people291-. Nosocomial transmission was not the main source of transmission in
China because of the implementation of infection control measures in clinical settings'. By contrast, a high risk of
nosocomial transmission was reported in some other
Image 196
transmission risk (228). Considering the zoonotic links associated with SARS-CoV-2, the One Health approach may
play a vital role in the prevention and control measures being followed to restrain this pandemic virus (317-319).
The substantial importation of COVID-19 pre symptomatic cases from Wuhan has resulted in independent, self-
sustaining outbreaks across major cities both within the country and across the globe. The majority of Chinese cities
are now facing localized outbreaks ofcOVID-19 (231). Hence, deploying efficient public health interventions might
help to cut the spread of this virus globally the occurrence of coVID-19 infection on several cruise ships gave us a
preliminary idea regarding the transmission pattern of the disease. Cruise ships act as a closed environment and
provide an ideal setting for the occurrence of respiratory disease outbreaks. Such a situation poses a significant
threat to travelers, since people from different countries are on board, which favors the introduction of the pathogen
(320). Although nearly30 cruise ships from different countries have been found harboring COVID-19 infection, the
major cruise ships that were involved in the COVID-19outbreaks are the Diamond Princess, Grand Princess,
Celebrity Aper, and Ruby Princess. The
Image 197
vaccine that can produce Cross-reactive antibodies. However, the success of such a vaccine relies greatly on its
ability to provide protection not only against present versions of the virus but also the ones that are likely to emerge
in the future. This can be achieved by identifying antibodies that can recognize relatively conserved epitopes that are
maintained as such even after the occurrence of considerable variations (362). Even though several vaccine clinical
trials are being conducted around the world, pregnant women have been completely excluded from these studies.
Pregnant women are highly vulnerable to emerging diseases such as COVID-19due to alterations in the immune
system and other physiological systems that are associated with pregnancy. Therefore, in the event of successful
vaccine development, pregnant women will not get access to the vaccines (361). Hence, it is recommended that
pregnant women be included in the ongoing vaccine trials, since successful vaccination in pregnancy will protect the
mother, fetus, and newborn.
The heterologous immune effects induced by Bacillus Calmette Guérin (BCG) vaccination is a promising strategy
for controlling the COVID-19pandemic and requires further investigations. BCG is a widely used vaccine against
tuberculosis in high-
Image 198
of persistent local transmission or contact with patients with similar travel history or those with confirmedcoVID-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/
endotracheal 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 reference labs in India or the National Institute of Virology in Pune. As the epidemic progresses,
commercial tests
Image 199
including IL2, IL7, IL10, GCSE, P10, MCP1, MIP1A, and TNFa [15]. The median time from onset of symptoms to
dyspnea was 5 d, hospitalization 7 day acute respiratory distress syndrome (ARDS) 8 d. The need for intensive care
admission was in 25-30% 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% of fatal cases). Fatality rate in hospitalized adult patients ranged from
4 to 11%.The overall case fatality rate is estimated to range between 2 and 3%[2].Interestingly, disease in patients
outside Hubei province has been
Image 200
prevailing chronic medical conditions such as lung disease, heart failure, cancer, cerebrovascular disease, renal
disease, diabetes, liver disease and immunocompromising conditions and pregnancy are risk factors for developing
severe illness. Management includes implementation of prevention and control measures and supportive therapy to
manage the complications, together with advanced organsupport. 57 Corticosteroids must be avoided unless specified
for chronic obstructive pulmonary disease exacerbation or septic shock, as it is likely to prolong viral replication as
detected inMERS-CoV patients.58

12 EARLY SUPPORTIVETHERAPY AND MONITORING

Management of patients with suspected or documented COVID-19 consists of ensuring appropriate infection control
and supportive care. WHO and the CDC posted clinical guidance for COVID-19. 59 Immediate therapy of add-on
oxygen must be started for patients with severe acute respiratory infection (SARI) and respiratory