This will further result in the extensive transmission of COVID-19, since only a

portion of suspected cases can be diagnosed. In such situations, conventional

serological assays, like enzyme-linked immunosorbent assay (ELISA), that are
specific to COVID-19 IgM and IgG antibodies can be used as a high-throughput
alternative. At present, there is no diagnostic kit available for detecting the SARS
CoV-2 antibody. The specific antibody profiles of COVID-19 patients were
analyzed, and it was found that the IgM level lasted more than 1 month, indicating
a prolonged stage of virus replication in SARS-CoV-2-infected patients. The IgG
levels were found to increase only in the later stages of the disease. These findings
indicate that the specific antibody profiles of SARS-CoV-2 and SARS-CoV were
similar. These findings can be utilized for the development of specific diagnostic
tests against COVID-19 and can be used for rapid screening. Even though diagnostic
test kits are already available that can detect the genetic sequences of SARS-CoV-
2, their availability is a concern, as the number of COVID-19 cases is skyrocketing.
A major problem associated with this diagnostic kit is 216 countries and regions
from all six continents had reported more than 20 million cases of COVID-19, and
more than 733,000 patients had died. High mortality occurred especially when
health-care resources were overwhelmed. The USA is the country with the largest
number of cases so far. Although genetic evidence suggests that SARS-CoV-2 is a
natural virus that likely originated in animals, there is no conclusion yet about when
and where the virus first entered humans. As some of the first reported cases in
Wuhan had no epidemiological link to the seafood market", it has been suggested
that the market may not be the initial source of human infection with SARS-CoV-2.
One study from France detected SARS-CoV-2 by PCR in a stored sample from a
patient who had pneumonia at the end of 2019, suggesting SARS-CoV-2 might have
spread there much earlier than the generally known starting time of the outbreak in
France". However, this individual early report cannot give a solid answer to the
origin of SARS-CoV-2 and contamination, and thus a false positive result cannot be
excluded. To address this highly controversial issue, further retrospective
investigations involving a larger number of banked samples from patients, animals
and environments need to be conducted worldwide with well-validated assays.
Genomics, phylogeny and taxonomy:
As a novel beta coronavirus, SARS-CoV-2 shares 79% genome sequence identity
with SARS-CoV and 50% with MERS-CoV. Its genome organization is shared with
other beta coronaviruses. The six functional open reading frames (ORFs) are
arranged in order from 5' to 3': replicas (ORF1a/ORF1b), spike (S), envelope (E),
membrane (M) and nucleocapsid (N). In addition, seven putative ORFs encoding
accessory proteins are interspersed between the structural genes". Most of the
proteins encoded by SARS-CoV-2 have a similar risk regions. It is derived from a
live attenuated strain of Mycobacterium bovid. At present, three new clinical trials
have been registered to evaluate the protective role of BCG vaccination against
SARS CoV-2. 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. 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%).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.
As an entry receptor while exhibiting an RBD similar to that of SARS-CoV. Several
countries have provided recommendations to their people traveling to China.
Compared to the previous coronavirus outbreaks caused by SARS CoV and MERS-
CoV, the efficiency of SARS-CoV-2 human-to-human transmission was thought to
be less. This assumption was based on the finding that health workers were affected
less than they were in previous outbreaks of fatal coronaviruses. Super spreading
events are considered the main culprit for the extensive transmission of SARS and
MERS. Almost half of the MERS-CoV cases reported in Saudi Arabia are of
secondary origin that occurred through contact with infected asymptomatic or
symptomatic individuals through human-to-human transmission. The occurrence of
super spreading events in the COVID-19 outbreak cannot be ruled out until its
possibility is evaluated. Like SARS and MERS, COVID-19 can also infect the lower
respiratory tract, with milder symptoms. The basic reproduction number of COVID-
19 has been found to be in the range of 2.8 to 3.3 based on real-time reports and 3.2
to 3.9 based on predicted infected cases. 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.
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. It is also evident that remdesivir was effective in treating the patients
who were infected with Ebola virus. Per this evidence, China has already started
testing the efficacy of remdesivir in treating the patients with COVID-19, especially
in Wuhan, where the outbreak occurred. Chloroquine, which is an existing drug
which is currently used in treating malaria cases, was given to more than 100 patients
who were affected with novel coronavirus to test its efficacy. A metacentric study
was conducted in China to test the effectiveness of remdesivir in treating the patients
with COVID-19. Thus, the results of the clinical trial proved that remdesivir has a
considerably acceptable level of efficacy for treating the patients with COVID-19.
Therefore, the National Health Commission of the People's Republic of China
decided to include remdesivir in the Guidelines for the Prevention, Diagnosis and
Treatment of Pneumonia Caused by COVID 19. Chloroquine and
hydroxychloroquine are existing anti-malaria drugs also given to more than 30
patients infected with COVID-19 in Guangdong province and Hunan province to
test their effectiveness and efficacy. Thus, the results of the clinical trial showed that
the Based on molecular characterization, SARS CoV-2 is considered a new Beta
coronavirus belonging to the subgenus Sarbecovirus. A few other critical zoonotic
viruses (MERS-related CoV and SARS-related CoV) belong to the same genus.
However, SARS-CoV-2 was identified as a distinct virus based on the percent
identity with other Beta coronavirus; conserved open reading frame 1a/b (ORF1a/b)
is below 90% identity. An overall 80% nucleotide identity was observed between
SARS-CoV-2 and the original SARS-CoV, along with 89% identity with ZC45 and
ZXC21 SARS related CoVs of bats. In addition, 82% identity has been observed
between SARS-CoV-2 and human SARS-CoV Tor2 and human SARS-COV BJ01
2003. A sequence identity of only 51.8% was observed between MERS-related CoV
and the recently emerged SARS-CoV-2. Phylogenetic analysis of the structural
genes also revealed that SARS-CoV-2 is closer to bat SARS-related CoV. Therefore,
SARS-CoV-2 might have originated from bats, while other amplifier hosts might
have played a role in disease transmission to humans. Of note, the other two zoonotic
CoVs (MERS-related CoV and SARS-related CoV) also originated from bats.
Nevertheless, for SARS and MERS, civet into the host cell. Heptad repeat 1 (HRI)
and heptad repeat 2 (HR2) can interact and form a six-helix bundle that brings the
viral and cellular membranes in close proximity, facilitating its fusion. The sequence
alignment study conducted between COVID-19 and SARS-CoV identified that the
S2 subunits are highly conserved in these CoV. The HRI and HR2 domains showed
92.6% and 100% overall identity, respectively. From these findings, we can confirm
the significance of COVID-19 HR1 and HR2 and their vital role in host cell entry.
Hence, fusion inhibitors target the HR1 domain of S protein, thereby preventing viral
fusion and entry into the host cell. This is another potential therapeutic strategy that
can be used in the management of COVID-19. Other than the specific therapy
directed against COVID-19, general treatments play a vital role in the enhancement
of host immune responses against the viral agent. Inadequate nutrition is linked to
the weakening of the host immune response, making the individual more susceptible.
The role played by nutrition in disease susceptibility should be measured by
evaluating the nutritional status of patients with COVID-19.
Prevention:
Since at this time there are no approved treatments for this infection, prevention is
crucial. Several properties of this virus make prevention difficult namely,
nonspecific 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. Fatigue,
Individuals with asymptomatic and atypical clinical manifestations were also
identified recently. Further adding to the complexity of disease transmission
dynamics. Atypical clinical manifestations may only express symptoms such as
fatigue instead of respiratory signs such as fever, cough, and sputum. In such cases,
the clinician must be vigilant for the possible occurrence of asymptomatic and
atypical clinical manifestations to avoid the possibility of missed diagnoses. The
present outbreak caused by SARS-CoV-2 was, indeed, expected. Similar to previous
outbreaks, the current pandemic also will be contained shortly. However, the real
question is, how are we planning to counter the next zoonotic CoV epidemic that is
likely to occur within the next 5 to 10 years or perhaps sooner? Our knowledge of
most of the bat CoVs is scarce, as these viruses have not been isolated and studied,
and extensive studies on such viruses are typically only conducted when they are
associated with specific disease outbreaks. The next step following the control of the
COVID-19 outbreak in China should be focused on screening, identification,
isolation, and characterization of CoVs present in wildlife species of China,
particularly in bats. Both in vitro and in vivo studies (using suitable animal models)
should be conducted.
Serological testing:
Serological surveys are also considered to be one of the most effective ones in
facilitating outbreak investigation and it also helps us to derive a retrospective
assessment of the disease by estimating the attack rate. According to the recent
literature, paired serum samples can also help clinicians to diagnose COVID-19 in
case of false negative results in NAAT essays. The literature also declared that the
commercial and non-commercial serological tests are under consideration in order
to support the practicing clinicians by assisting them in diagnosis. Similarly, there
are studies published on COVID-19 which are comprised of the serological data on
clinical samples.
Viral sequencing:
Apart from confirming the presence of virus in the specimens, viral sequencing is
also quite useful in monitoring the viral genomic mutations, which plays a very
significant role in influencing the performance of the medical countermeasures
inclusive of the diagnostic test. Genomic sequencing of the virus can also help
further in developing several studies related to molecular epidemiology, specifically
in the respiratory tract will help to reduce virus-triggered immune pathologies in
COVID-19. 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-1 family. 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. 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. A scientist from Germany, named Rolf Hilgenfeld, has been working on
the identification of drugs for the treatment of corona viral infection since the time
of the first SARS outbreak. The SARS-CoV S2 subunit has a significant function in
mediating virus fusion that provides entry into the host cell. Heptad repeat 1 (HR1)
and heptad developed for rapid and colorimetric detection of this virus. RT-LAMP
serves as a simple, rapid, and sensitive diagnostic method that does not require
sophisticated equipment or skilled personnel. An interactive web-based dashboard
for tracking SARS-CoV-2 in a real-time mode has been designed. 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. 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. 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. A CRISPR-Cas 12-based
lateral flow assay also has been developed for rapid detection of SARS-CoV-2.
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.
Tracking and mapping of the rising incidence. Rates, disease outbreaks, community
spread. Furthermore, SARS-CoV-2 is genetically distinct from SARS-CoV (79%
similarity) and MERS-CoV (nearly 50%). COVID-19 is associated with afflictions
of the lungs in all cases and generated characteristic chest computer tomography
findings, such as the presence of multiple lesions in lung lobes that appear as dense,
ground-glass opaque structures that occasionally coexist with consolidation
shadows. Absence of this protein is related to the altered virulence of coronaviruses
due to changes in morphology and tropism. The E protein consists of three domains,
namely, a short hydrophilic amino terminal, a large hydrophobic transmembrane
domain, and an efficient C-terminal domain. The SARS-CoV-2 E protein reveals a
similar amino acid constitution without any substitution.
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 vision assembly, and enhances the transcription efficiency of the
virus. It contains three highly conserved and distinct domains, namely, an NTD, an
RNA-binding domain or a linker region (LKR), and a CTD. The NTD binds with
the 3' end of the viral genome, perhaps via electrostatic interactions, and is highly
diverged both in length and sequence. The charged LKR is serine and arginine rich
and is also known as the SR (serine and arginine) domain. The LKR is capable of
direct interaction with in vitro RNA interaction and is responsible for cell signaling.
It also modulates the antiviral response of the host by working as an antagonist for
interferon assessed intrauterine vertical transmission of COVID-19 infection in nine
infants born to infected mothers, found that none of the infants tested positive for
the virus. Likewise, there was no evidence of intrauterine infection caused by
vertical transmission in the SARS and MERS epidemics. The CDC asserts that
infants born to mothers with confirmed COVID-19 are considered persons under
investigation (PUI) and should be temporarily separated from the mother and
isolated.
Breastfeeding and infant care:
The data available to date is limited and cannot confirm whether or not COVID-19
can be transmitted through breast milk. Assessing the presence of COVID-19 in
breast milk samples from six patients showed negative result. The CDC points out
that in case of a confirmed or suspected COVID-19 infection, the decision of
whether or how to start or continue breastfeeding should be made by the mother in
collaboration with the family and healthcare practitioners. Careful precautions need
to be taken by the mother to prevent transmitting the disease to her infant through
respiratory droplets during breastfeeding. This includes wearing a facemask and
practicing hand interactions remain largely unclear. Intensive studies on these
biological profiles of SARS-CoV-2 will provide the basis for the development of
preventive and there peptic strategies against COVID-19. Moreover, contain used
genomic monitoring of SARS-CoV-2 in new cases is needed worldwide, as it is
important to promptly identify any mutation that may result in phenotypic changes
of the virus. Finally, COVID-19 is challenging all human beings. Tackling this
epidemic is a long-term job which requires efforts of every individual, and
international collaborations by scientists, authorities and the public. 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. As of 13 May 2020, SARS-CoV-2
confirmed cases have been reported in more than 210 countries apart from China.
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 up pies can spread 1-2 in a posit on surfaces. The virus can remain viable
on surfaces for days in favorable atmospheric conditions but are destroyed in less
than a minute by common disinfectants like sodium hypochlorite, hydrogen peroxide
etc. Infection is acquired either by inhalation of these droplets or touching surfaces
contaminated by them or 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 aerosolization/face oral route is also hypothesized. Transmission
from pregnant women to their fetus has not been described. However, neonatal
disease due to post-natal transmission is described. The incubation period varies
from 2 to 14 d [median 5 d]. Studies have identified angiotensin receptor 2 length to
the corresponding proteins in SARS-CoV. Of the four structural genes, SARS-CoV-
2 shares more than 90% amino acid identity with SARS-CoV except for the S gene,
which diverges. The replicas gene covers two thirds of the 5' genome, and encodes
a large polyprotein, which is proteolytic ally cleaved into 16 non-structural proteins
that are involved in transcription and virus replication. Most of these SARS-CoV-2
non-structural proteins have greater than 85% amino acid sequence identity with
SARS-CoV25. The phylogenetic analysis for the whole genome shows that SARS-
CoV-2 is clustered with SARS-CoV and SARS-related coronaviruses (SARS-CoVs)
found in bats, placing it in the subgenus Sarbecovirus of the genus Beta coronavirus.
Within this clade, SARS-CoV-2 is grouped in a distinct lineage together with four
horse shoe bat coronavirus isolates (RaTG13, RmYN02, ZC45 and ZXC21) as well
as novel coronaviruses recently identified in pangolins, which group parallel to
SARS-CoV require sedatives, analgesics, and even muscle relaxation drugs to
prevent ventilator-related lung injury associated with human-machine
incoordination. The result obtained from a clinical study of four patients infected
with COVID 19 claimed that combination therapy using lopinavir/ritonavir, arborol,
and Snuffing Jibed capsules (traditional Chinese medicine) was found to be effective
in managing COVID-19 pneumonia. It is difficult to evaluate the therapeutic
potential of a drug or a combination of drugs for managing a disease based on such
a limited sample size. Before choosing the ideal therapeutic agent for the
management of COVID-19, randomized clinical control studies should be performed
with a sufficient study population.
Antiviral Drugs:
Several classes of routinely used antiviral drugs, like oseltamivir (neuraminidase
inhibitor), acyclovir, ganciclovir, and ribavirin, do not have any effect on COVID-
19 and, hence, are not recommended. Oseltamivir, a neuraminidase inhibitor, has
been explored in Chinese hospitals for treating suspected COVID-19 cases, although
proven efficacy against SARS-CoV-2 is still lacking for this drug. The in vitro
antiviral potential of FAD-approved drugs, viz. SARS- or MERS-CoV outbreak,
however, there has been concern regarding the impact of SARS-CoV-2/COVID-19
on pregnancy. Researchers have mentioned the probability of in utero transmission
of novel SARS-CoV-2 from COVID 19-infected mothers to their neonates in China
based upon the rise in IgM and IgG antibody levels and cytokine values in the blood
obtained from newborn infants immediately post birth; however, RT-PCR failed to
confirm the presence of SARS-CoV-2 genetic material in the infants. Recent studies
show that at least in some cases, preterm delivery and its consequences are
associated with the virus. Nonetheless, some cases have raised doubts for the
likelihood of vertical transmission. COVID-19 infection was associated with
pneumonia, and some developed acute respiratory distress syndrome (ARDS). The
blood biochemistry indexes, such as albumin, lactate dehydrogenase, C reactive
protein, lymphocytes (percent), and neutrophils (percent) give an idea about the
disease severity in COVID-19 infection. During COVID-19, patients may present
leukocytosis, leukopenia with lymphopenia, hypoalbuminemia, and an increase of
lactate dehydrogenase, aspartate transaminase, alanine aminotransferase, bilirubin,
and, especially, D-dimer. We also predict the possibility of another outbreak, as
predicted by Fan etc. Indeed, the present outbreak caused by SARS-CoV-2 (COVID
19) was expected. Similar to previous outbreaks, the current outbreak also will be
contained shortly. However, the real issue is how we are planning to counter the next
zoonotic CoV epidemic that is likely to occur within the next 5 to 10 years or even
sooner The results of the studies related to SARS-CoV-2 viral loads reflect active
replication of this virus in the upper respiratory tract and prolonged viral shedding
after symptoms disappear, including via stool. Thus, the current case definition
needs to be updated along with a reassessment of the strategies to be adopted for
restraining the SARS-CoV-2 outbreak spread. In some cases, the viral load studies
of SARS-CoV-2 have also been useful to recommend precautionary measures when
handling specific samples, e.g., feces. In a recent survey from 17 confirmed cases of
SARS-CoV-2 infection with available data (representing days 0 to 13 after onset),
stool samples from nine cases (53%; days 0 to 11 after onset) were positive on RT-
PCR analysis. Although the viral loads were lower than those of respiratory samples
(range, 550 copies per ml to 1.21 x 105 copies per ml), this has essential biosafety
implications.
The samples from 18 SARS-CoV-2-positive patients in Singapore who had traveled
from Wuhan to Singapore showed the presence of viral RNA in stool and whole
blood but not in urine by real-time RT-PCR. Further, novel SARS-CoV-2 infections
have been detected in a variety of clinical specimens, like Broncho alveolar lavage
fluid, 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.
Differential Diagnosis:
The differential diagnosis includes all types of respiratory viral infections [influenza,
parainfluenza, respiratory syncytial virus (RSV), adenovirus, human
metapneumovirus, and 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.
PREVENTION:
The WHO and other agencies such as the CDC have published protective measures
to mitigate the spread of COVID-19. This involves frequent hand washing with hand
wash containing 60% of alcohol and soap for at least 20 seconds. Another important
measure is avoiding close contact with sick people and keeping a social distance of
1 meter always to everyone who is coughing and sneezing. Not touching the nose,
eyes and mouth was also suggested. While coughing or sneezing, covering the mouth
and nose with a cloth/tissue or the bent elbow is advised. Staying at home is
recommended for those who are sick, and wearing a facial mask is advised when
going out among people. Furthermore, it is recommended to clean and sterilize
frequently touched surfaces such as phones and doorknobs on a daily basis. Staying
at home as much as possible is advisable for those who are at higher risk for severe
illness, to minimize the risk of exposure to COVID-19 during outbreaks.
Viral replication:
Usually replication of coronavirus occurs within the cytoplasm and is closely
associated with endoplasmic reticulum and other cellular membrane organelles.
Human coronaviruses are thought to invade cells, primarily through different
receptors. For 229E and OC43, amino peptidase-N (AP-N) and a sialic acid
containing receptor, respectively, were known to function in this role. After the virus
enters the host cell and uncrating process occurs, the genome is transcribed, and
then, translated. A characteristic feature of replication is that all mRNAs form an
enclosed group of typical 3' ends; only the special portions of the 5' ends are
translated. In total, about 7 mRNAs are produced. The shortest mRNA codes and the
others can express the synthesis of another genome segment for nucleoprotein. At
the cell membrane, these proteins are collected and genomic RNA is initiated as a
mature particle type by burgeoning from internal cell membranes.
PATHOGENESIS:
Coronaviruses are tremendously precise and mature in most of the airway epithelial
cells as observed through both in vivo and in vitro polymorphism at nucleotide
position 28,144, which results in amino acid substitution of Seer for Lys at residue
of the ORF8 protein. Those variants with this mutation make up a single subclade
labelled as 'clade S'5334 Currently, however, the available sequence data are not
sufficient to interpret the early global transmission history of the 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 affine 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 dovely clusters with RaTG13.
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 Malayans bat sampled
in Yunnan This novel hat virus denoted 'RmYN02'. 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. In 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. 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-CoV 2 surface glycoprotein. The selected epitopes explored targeting
molecular dynamic simulations. From experience with several outbreaks associated
with known emerging viruses, higher pathogenicity of a virus is often associated
with lower transmissibility. Compared to emerging viruses like Ebola virus, avian
H7N9, SARS-CoV, and MERS-CoV, SARS-CoV-2 has relatively lower
pathogenicity and moderate transmissibility. The risk of death among individuals
infected with COVID-19 was calculated using the infection fatality risk (IFR). The
IFR was found to be in the range of 0.3% to 0.6%, which is comparable to that of a
previous Asian influenza pandemic (1957 to 1958). Notably, the reanalysis of the
COVID-19 pandemic curve from the initial cluster of cases pointed to considerable
human-to-human transmission. It is opined that the exposure history of SARS-CoV-
2 at the Wuhan seafood market originated from human-to-human transmission rather
than animal-to-human transmission; however, in light of the zoonotic spillover in
COVID-19, is too early to fully endorse this idea. Following the initial infection,
human-to-human transmission has been observed with a preliminary reproduction
number (Ro) estimate of 1.4 to 2.5, and recently it is estimated to be 2.24 to 3.58. In
another study, the average reproductive number of 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.
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 infection 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 travelers 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.
Inhibition of virus replication:
Replication inhibitors include remdesivir (GS-5734), failover (T-705), rib virgin,
lopinavir and ritonavir. Except for lopinavir and ritonavir, which inhibit 3CLpro, the
other three all target. Remdesivir has shown activity against SARS-CoV-2 in vitro
and in vivo. A clinical study revealed a lower need for oxygen support in patients
with COVID-19 (REF.), 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 significant. The FDA has issued an
emergency use authorization for rem deliver 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 adores cents with pneumonia requiring
supplemental oxygen. Several international phase III clinical trials are contain using
to evaluate the safety and efficacy of remdesivir for the treatment of COVID-19.
Failover (T-705), which is an antiviral drug devil opted 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 failover 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 failover 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.
CONVALESCENT PLASMA THERAPY:
Guo Yanhong, an official with the National Health Commission (NHC), stated that
convalescent plasma therapy is a 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 1st 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 minimized 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 milliliters. Only a matter of time before another
zoonotic coronavirus results in an epidemic by jumping the so-called species barrier.
The host spectrum of coronavirus increased when a novel coronavirus, namely,
SW1, was recognized in the liver tissue of a captive beluga whale (Delphinapterus
Lucas). 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. 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. 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 Beta coronavirus among
animals, especially in the Rhinolophus bat family. Chinese bats have high
commercial value, since they are used in.
INTRODUCTION
Over the past 2 decades, coronaviruses (CoVs) have been associated with significant
disease outbreaks in East Asia and the Middle East. The severe acute respiratory
syndrome (SARS) and the Middle East respiratory syndrome (MERS) began to
emerge in 2002 and 2012, respectively. Recently, a novel coronavirus, severe acute
respiratory syndrome coronavirus (SARS-CoV-2), causing coronavirus disease
2019 (COVID-19), emerged in late 2019, and it has posed a global health threat,
causing an ongoing pandemic in many countries and territories. Health workers
worldwide are currently making efforts to control further disease outbreaks caused
by the novel CoV (originally named 2019-nCoV), which was first identified in
Wuhan City, Hubei Province, China, on 12 December 2019. On 11 February 2020,
the World Health Organization (WHO) announced the official designation for the
current CoV-associated disease to be COVID-19, caused by SARS-CoV-2. The
primary cluster of patients was found to be connected with the Huanan South China
Seafood Market in Wuhan. CoVs belong to the family Coronaviridae (subfamily
Coronavirinae), the members of which infect a broad visible signs of infection,
making it challenging to identify animals actively excreting MERS-CoV that has the
potential to infect humans. However, they may shed MERS-CoV through milk,
urine, feces, and nasal and eye discharge and can also be found in the raw organs. In
a study conducted to evaluate the susceptibility of animal species to MERS-CoV
infection, llamas and pigs were found to be susceptible, indicating the possibility of
MERS CoV circulation in animal species other than dromedary camels. Following
the outbreak of SARS in China, SARS-CoV-like viruses were isolated from
Himalayan palm civets (Pauma lariat) and raccoon dogs (Nyctereutes procyonoides)
found in a live-animal market in Guangdong, China. The animal isolates obtained
from the live-animal market retained a 29-nucleotide sequence that was not present
in most of the human isolates. These findings were critical in identifying the
possibility of interspecies transmission in SARS-CoV. The higher diversity and
prevalence of bat coronaviruses in this region compared to those in previous reports
indicate a host/pathogen coevolution. SARS-like coronaviruses also have been
found circulating in the Chinese horseshoe bat (Rhinolophus sinuous) populations.
The newly developed drugs cannot be marketed due to the lack of end users.
Vaccines:
The S protein plays a significant role in the induction of protective immunity against
SARS-CoV by mediating T-cell responses and neutralizing antibody production. In
the past few decades, we have seen several attempts to develop a vaccine against
human coronaviruses by using S protein as the target. However, the developed
vaccines have minimal application, even among closely related strains of the virus,
due to a lack of cross-protection. That is mainly because of the extensive diversity
existing among the different antigenic variants of the virus. The contributions of the
structural proteins, like spike (S), matrix (M), small envelope (E), and nucleocapsid
(N) proteins, of SARS-CoV to induce protective immunity has been evaluated by
expressing them in a recombinant parainfluenza virus type 3 vector (BHPIV3). Of
note, the result was conclusive that the expression of M, E, or N proteins without the
presence of S protein would not comprised a small population and, hence, the
possibility of misinterpretation could arise. However, in another case study, the
authors raised concerns over the efficacy of hydroxychloroquine azithromycin in the
treatment of COVID-19 patients, since no observable effect was seen when they
were used. In some cases, the treatment was discontinued due to the prolongation of
the QT interval. Hence, further randomized clinical trials are required before
concluding this matter. Recently, another FDA-approved drug, ivermectin, was
reported to inhibit the in vitro replication of SARS-CoV-2. The findings from this
study indicate that a single treatment of this drug was able to induce an -5,000-fold
reduction in the viral RNA at 48 h in cell culture. One of the main disadvantages that
limit the clinical utility of ivermectin is its potential to cause cytotoxicity. However,
altering the vehicles used in the formulations, the pharmacokinetic properties can be
modified, thereby having significant control over the systemic concentration of
ivermectin. Based on the pharmacokinetic simulation, it was also found that
ivermectin may have limited therapeutic utility in managing COVID-19, since the
inhibitory concentration that has to be achieved for effective anti-SARS-CoV-2
activity is far higher than the respiratory syncytial virus, rhinovirus, and human
metapneumovirus and SARS coronavirus. It is advisable to distinguish COVID-19
from other pneumonias such as mycoplasma pneumonia, chlamydia pneumonia and
bacterial pneumonia. 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.
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). 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. In addition to
RaTG13 and RmYN02, phylogenetic analysis shows that bat coronaviruses ZC45
and ZXC21 previously detected in Rhinolophus poilus bats from eastern China also
fall into the SARS-CoV-2 lineage of the subgenus Sarbecovirus". The discovery of
diverse bat coronaviruses closely related to SARS-CoV-2 suggests that bats are
possible reservoirs of SARS-CoV-2. 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. 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 pro vicinal 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 article gives a
bird's eye view about 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. 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 beta corona viruses to humans has resulted
in severe disease. The first such instance was in 2002-2003 when a Chloroquine and
hydroxychloroquine are other potential but controversial drugs that interfere with
the entry of SARS-CoV-2. They have been used in the prevention and treatment of
malaria and autoimmune diseases, including systemic lupus erythematosus and
rheumatoid arthritis. They can inhibit the glycosylation of cellular receptors and
interfere with virus-host receptor binding, as well as increase the endosomal pH and
inhibit membrane fusion. Currently, no scientific consensus has been reached for
their efficacy in the treatment of COVID-19. Some studies showed they can inhibit
SARS-CoV-2 infection in vitro, but the clinical data are insufficient. Two clinical
studies indicated no association with death rates in patients receiving chloroquine or
hydroxychloroquine compared with those not receiving the drug and even suggest it
may increase the risk of dying as a higher risk of cardiac arrest was found in the
treated patients. On 15 June 2020, owing to the side effects observed in clinical trials,
the US Food and Drug Administration (FDA) revoked the emergency use
authorization for chloroquine and hydroxychloroquine for the treatment of COVID-
19. Another potential therapeutic strategy is to block binding of the S protein to
ACE2 through soluble recombinant hACE2, specific monoclonal antibodies or
fusion inhibitors that target the SARS-CoV-2 S protein. The safety and efficacy of
these strategies need to be assessed in future clinical trials. Glass opacities and sub
segmental 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.
Differential Diagnosis:
The differential diagnosis includes all types of respiratory viral infections [influenza,
parainfluenza, respiratory syncytial virus (RSV), adenovirus, human
metapneumovirus, and 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 severe illness, to
minimize the risk of exposure to COVID-19 during outbreaks.
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 Napping,
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. 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. 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 RBD specific neutralizing MAs considerably
relies on the resemblance between their RBDs; therefore, SARS-CoV RBD-specific
antibodies could cross neutralized SL CoVs, i.e., bat-SL-CoV strain WIVI (RBD
with eight amino acid differences from SARS CoV) but not bat-SL-CoV strain
SHC014 (24 amino acid differences). Appropriate RBD-specific MAbs can be
recognized by a relative analysis of RBD of SARS CoV-2 to that of SARS-CoV,
and cross-neutralizing SARS-CoV RBD-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. The SARS-CoV-specific human MAb CR3022 is found to bind with
SARS-CoV-2 RBD, indicating its potential as a therapeutic agent. The
comprehensive sequence analysis of the SARS-CoV-2 RNA genome identified that
the CoV from Wuhan is a recombinant virus of the bat coronavirus and another
coronavirus of unknown origin. The recombination was found to have happened
within the viral spike glycoprotein, which recognizes the cell surface receptor.
Further analysis of the genome based on codon usage identified the snake as the
most probable animal reservoir of SARS-CoV-2. Contrary to these findings, another
genome analysis proposed that the genome of SARS-CoV-2 is 96% identical to bat
coronavirus, reflecting its origin from bats. The involvement of bat-derived materials
in causing the current outbreak cannot be ruled out. High risk is involved in the
production of bat-derived materials for TCM practices involving the handling of
wild bats. The use of bats for TCM practices will remain a severe risk for the
occurrence of zoonotic coronavirus epidemics in the future. Furthermore, the
pangolins are an endangered species of animals that harbor a wide variety of viruses,
including coronaviruses. The coronavirus isolated from Malayan pangolins (Mani’s
javanica) showed a very high amino acid identity with COVID-19 at E (100%), M
(98.2%), N (96.7%), and S genes (90.4%). The RBD of S protein Princess, Celebrity
Apex, and Ruby Princess. The number of confirmed COVID-19 cases around the
world is on the rise. The success of preventive measures put forward by every
country is mainly dependent upon their ability to anticipate the approaching waves
of patients. This will help to properly prepare the health care workers and increase
the intensive care unit (ICU) capacity. Instead of entirely relying on lockdown
protocols, countries should focus mainly on alternative intervention strategies, such
as large-scale testing, contract tracing, and localized quarantine of suspected cases
for limiting the spread of this pandemic virus. Such intervention strategies will be
useful either at the beginning of the pandemic or after lockdown relaxation.
Lockdown should be imposed only to slow down disease progression among the
population so that the health care system is not overloaded. The reproduction number
(R) of COVID-19 infection was earlier estimated to be in the range of 1.4 to 2.5;
recently, it was estimated to be 2.24 to 3.58. Compared to its coronavirus
predecessors, COVID-19 has a Ro value that is greater than that of MERS (Ro< 1)
but less than that of SARS (Ro value of 2 to 5). Still, to prevent further spread of
disease at mass gatherings. Shedding the virus, which may remain viable for at least
3 days and is considered a great risk for uninfected patients and health care workers.
Recently, it was found that the anal swabs gave more positive results than oral swabs
in the later stages of infection. Hence, clinicians have to be cautious while
discharging any COVID-19-infected patient based on negative oral swab test results
due to the possibility of fecal-oral transmission. Even though the viral loads in stool
samples were found to be less than those of respiratory samples, strict precautionary
measures have to be followed while handling stool samples of COVID-19 suspected
or infected patients. Children infected with SARS-CoV-2 experience only a mild
form of illness and recover immediately after treatment. It was recently found that
stool samples of SARS-CoV-2 infected children that gave negative throat swab
results were positive within ten days of negative results. This could result in the
fecal-oral transmission of SARS-CoV-2 infections, especially in children. Hence, to
prevent the fecal-oral transmission of SARS-CoV-2, infected COVID-19 patients
should only be considered negative when they test negative for SARS-CoV-2 in the
stool sample.SARS-CoV-2 invades the lung parenchyma, resulting in severe
interstitial inflammation of the lungs. This is evident on computed tomography (CT)
images as ground-glass opacity in the lungs. This lesion initially involves a single
lobe but later expands to multiple lung lobes. The histological assessment of lung
biopsy samples obtained from COVID-19-infected patients revealed diffuse alveolar
damage, cellular fibromyxoid exudates, hyaline membrane formation, and
desquamation of pneumocystis, indicative of acute respiratory distress syndrome. It
was also found that the SARS-CoV-2-infected patients often have lymphocytopenia
with or without leukocyte abnormalities. The degree of lymphocytopenia gives an
idea about disease prognosis, as it is found to be positively correlated with disease
severity. Pregnant women are considered to have a higher risk of getting infected by
COVID-19. The coronaviruses can cause adverse outcomes for the fetus, such as
intrauterine growth restriction, spontaneous abortion, preterm delivery, and perinatal
death. Nevertheless, the possibility of intrauterine maternal-fetal transmission
(vertical transmission) of CoVs is low and was not seen during either the SARS- or
MERS-CoV outbreak. Identified angiotensin receptor 2 (ACE) as the receptor
through which the virus enters the respiratory mucosa. The basic case reproduction
rate (BCR) is estimated to range from 2 to 6.47 in various modelling studies. In
comparison, the BCR of SARS was 2 and 1.3 for pandemic flu H1N1 2009.
Clinical Features:
The clinical features of COVID-19 are varied, ranging from asymptomatic state to
acute respiratory distress syndrome and multi organ dysfunction. The common
clinical features include fever (not in all). Cough, sore throat, headache, fatigue,
headache, myalgia and breathlessness. Conjunctivitis has also been described.
Environmental samples from the Huanan sea food market also tested positive,
signifying that the virus originated from there. 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. The
first fatal case was reported on 11th Jan 2020. The massive migration of Chinese
during the Chinese New Year fueled 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. 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. Due to fear of virus spread, Wuhan City was completely shut down. 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. 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. The interferon response is one of
the major innate immunity defenses against virus invasion. Interferons induce the
expression of diverse interferon-stimulated genes, which can interfere with every
step of virus replication. Previous studies identified type I interferons as a promising
therapeutic candidate for SARS In vitro data showed SARS-CoV-2 is even more
sensitive to type I interferons than SARS-CoV, suggesting the potential
effectiveness of type I interferons in the early treatment of COVID-19. In China,
vapor inhalation of interferon is included in the COVID-19 treatment guidelines.
Clinical trials are ongoing across the world to evaluate the efficacy of different
therapies involving interferons, either alone or in combination with other agents
Immunoglobulin therapy:
 Convalescent plasma treat mint is another potential adjunctive therapy for COVID-
19. Preliminary findings have suggested improved clinical status after the treatment.
The FDA has provided guidance for the use of COVID-19 convalescent plasma
under an emergency investigational new drug application. However, this treatment
may have adverse effects by causing antibody-mediated enhance mint of infection,
transfusion-associated acute lung injury and allergic transfusion reactions.
Monoclonal antibody therapy is an effective immune therapy for the treatment of
some viral infections in select patients. 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 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%.They potentially
induce immune responses. The recombinant vaccine can be designed by using rabies
virus (RV) as a viral vector. RV can be made to express MERS-CoV S1 protein on
its surface so that an immune response is induced against MERS-CoV. The RV
vector-based vaccines against MERS-CoV can induce faster antibody response as
well as higher degrees of cellular immunity than the Gram-positive enhancer matrix
(GEM) particle vector-based vaccine. However, the latter can induce a very high
antibody response at lower doses. Hence, the degree of humoral and cellular immune
responses produced by such vaccines depends upon the vector used. Dual vaccines
have been getting more popular recently. Among them, the rabies virus-based
vectored vaccine platform is used to develop vaccines against emerging infectious
diseases. The dual vaccine developed from inactivated rabies virus particles that
express the MERS-CoV S1 domain of S protein was found to induce immune
responses for both MERS-CoV and rabies virus. The vaccinated mice were found to
be completely protected from challenge with MERS-CoV.
CLINICAL DIAGNOSIS:
The symptoms of COVID-19 remain very similar to those of the other respiratory
epidemics in the past, which include SARS and MERS, but here the range of
symptoms includes mild rhinitis to septic shock. Some intestinal disturbances were
reported with the other epidemics, but COVID-19 was devoid of such symptoms.
When examined, unilateral or bilateral involvement compatible with viral
pneumonia is observed in the patients, and bilateral multiple lobular and sub-
segmental consolidation areas were observed in patients hospitalized in the intensive
care unit. Comorbid patients showed a more severe clinical course than predicted
from previous epidemics. Diagnosis of COVID-19 includes the complete history of
travel and touch, with laboratory testing. It is more preferable to choose serological
screening, which can help to analyses even the asymptomatic infections; several
serological tests are in progress for SARS-COV-2. However, ivermectin, being a
host-directed agent, exhibits antiviral activity by targeting a critical cellular process
of the mammalian cell. Therefore, the administration of ivermectin, even at lower
doses, will reduce the viral load at a minor level. This slight decrease will provide a
great advantage to the immune system for mounting a large-scale antiviral response
against SARS-CoV-2. Further, a combination of ivermectin and
hydroxychloroquine might have a synergistic effect, since ivermectin reduces viral
replication, while hydroxychloroquine inhibits the entry of the virus in the host cell.
Further, in vivo studies and randomized clinical control trials are required to
understand the mechanism as well as the clinical utility of this promising drug.
Nafamostat is a potent inhibitor of MERS-COV that acts by preventing membrane
fusion. Nevertheless, it does not have any sort of inhibitory action against SARS-
CoV-2 infection. Recently, several newly synthesized halogenated triazole
compounds were evaluated, using fluorescence resonance energy transfer (FRET)
based helicase assays, for their ability to inhibit or even die, whereas most young
people and children have only mild diseases (non-pneumonia or mild pneumonia) or
are asymptomatic. Notably, the 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 case. On infection, the
most common symptoms are fever, fatigue and dry cough. Less common symptoms
include sputum production, headache, hemoptysis, diarrhea, anorexia, sore throat,
chest pain, chills and nausea and vomiting in studies of patients in China. Self-
reported olfactory and taste disorders were also reported by patients in Italy. Most
people showed signs of diseases after an incubation period of 1-14 days (most
commonly around 5 days), and dyspnea and pneumonia developed within a median
time of 8 days from illness onset. In a report of 72,314 cases in China, 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). On admission,
ground-glass opacity was the most common radiologic finding on chest computed
tomography (CT). Most patients also developed marked lymphopenia, similar to
what was observed in patients with SARS and MERS, and non-survivors developed
severer lymphopenia over time. Compared with non-ICU patients, ICU patients had
higher levels. Coronavirus is the most prominent example of a virus that has crossed
the species barrier twice from wild animals to humans during SARS and MERS
outbreaks. The possibility of crossing the species barrier for the third time has also
been suspected in the case of SARS-CoV-2 (COVID-19). Bats are recognized as a
possible natural reservoir host of both SARS-CoV and MERS-CoV infection. In
contrast, the possible intermediary host is the palm civet for SARS-CoV and the
dromedary camel for MERS-CoV infection. Bats are considered the ancestral hosts
for both SARS and MERS. Bats are also considered the reservoir host of human
coronaviruses like HCoV-229E and HCOV-NL63. In the case of COVID-19, there
are two possibilities for primary transmission: it can be transmitted either through
intermediate hosts, similar to that of SARS and MERS, or directly from bats. The
emergence paradigm put forward in the SARS outbreak suggests that SARS-CoV
originated from bats (reservoir host) and later jumped to civets (intermediate host)
and incorporated changes within the receptor-binding domain (RBD) to improve
binding to civet ACE2. This civet-adapted virus, during their subsequent exposure
to humans at live markets, promoted further adaptations that resulted in the epidemic
strain. Transmission can also involve in the COVID-19 outbreak is of great
importance, b her bent oriental well Press Esc to exit full screen being will
affectation, concentration, and decision-making capacity. Hence, for control of the
COVID-19 outbreak, rapid steps should be taken to protect the mental health of
medical workers. Since the living mammals sold in the wet market are suspected to
be the intermediate host of SARS CoV-2, there is a need for strengthening the
regulatory mechanism for wild animal trade. The total number of COVID-19
confirmed cases is on a continuous rise and the cure rate is relatively low, making
disease control very difficult to achieve. The Chinese government is making
continuous efforts to contain the disease by taking emergency control and prevention
measures. They have already built a hospital for patients affected by this virus and
are currently building several more for accommodating the continuously increasing
infected population. The effective control of SARS CoV-2/COVID-19 requires
high-level interventions like intensive contact tracing, as well as the quarantine of
people with suspected infection and the isolation of infected individuals. The
implementation of rigorous control and preventive measures together might control
the Ro number and reduce the transmission risk. Considering the zoonotic suffering
from novel SARS-CoV-2, with more than 4,170,424 cases and 287,399 deaths
across the globe. There is an urgent need for a rational international campaign
against the unhealthy food practices of China to encourage the sellers to increase
hygienic food practices or close the crude live-dead animal wet markets. There is a
need to modify food policies at national and international levels to avoid further life
threats and economic consequences from any emerging or reemerging pandemic due
to close animal-human interaction. Even though individuals of all ages and sexes are
susceptible to COVID-19, older people with an underlying chronic disease are more
likely to become severely infected. Recently, individuals with asymptomatic
infection were also found to act as a source of infection to susceptible individuals.
Both the asymptomatic and symptomatic patients secrete similar viral loads, which
indicates that the transmission capacity of asymptomatic or minimally symptomatic
patients is very high. Thus, SARS-CoV-2 transmission can happen early in the
course of infection. Atypical clinical manifestations have also been reported in
COVID-19 in which the only reporting symptom was fatigue. Such patients may
lack respiratory signs, such as fever, cough, and sputum. Coronaviruses are a diverse
group of viruses infecting many different animals, and they can cause mild to severe
respiratory infections in humans. In 2002 and 2012, respectively, two highly
pathogenic coronaviruses with zoonotic origin, severe acute respiratory syndrome
coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus
(MERS-CoV), emerged in humans and caused fatal respiratory illness, making
emerging coronaviruses a new public health concern in the twenty-first century. At
the end of 2019, a novel coronavirus designated as SARS-CoV-2 emerged in the city
of Wuhan, China, and caused an outbreak of unusual viral pneumonia. Being highly
transmissible, this novel coronavirus disease, also known as coronavirus disease
2019 (COVID-19), has spread fast all over the world". It has overwhelmingly
surpassed SARS and MERS in terms of both the number of infected people and the
spatial range of epidemic areas. The ongoing outbreak of COVID-19 has posed an
extraordinary threat to global public health. In this Review, we summarize the
current understanding of the nature of SARS-CoV-2 and COVID-19. On the basis
of recently published findings, this comprehensive Review covers the basic biology
of SARS-CoV-2, including the genetic characteristics, the potential zoonotic origin
and its receptor binding. Furthermore, we will discuss the clinical and
epidemiological features, diagnosis of and countermeasures against COVID-19.
Emergence and spread:
In late December 2019, several health facilities in Wuhan, in Hubei province in
China, reported clusters of patients with pneumonia of unknown cause. Similarly to
patients with SARS and MERS, these patients showed symptoms of viral
pneumonia, including fever, cough. Even though a high similarity has been reported
between the genome sequence of the new coronavirus (SARS-CoV-2) and SARS-
like CoVs, the comparative analysis recognized a furan-like cleavage site in the
SARS-CoV-2 S protein that is missing from other SARS-like CoVs. The furan like
cleavage site is expected to play a role in the life cycle of the virus and disease
pathogenicity and might even act as a therapeutic target for furan inhibitors. The
highly contagious nature of SARS CoV-2 compared to that of its predecessors might
be the result of a stabilizing mutation that occurred in the endosome-associated-
protein-like domain of nsp2 protein. Similarly, the destabilizing mutation near the
phosphatase domain of nsp3 proteins in SARS-CoV 2 could indicate a potential
mechanism that differentiates it from other CoVs. Even though the CFR reported for
COVID-19 is meager compared to those of the previous SARS and MERS
outbreaks, it has caused more deaths than SARS and MERS combined. Possibly
related to the viral pathogenesis is the recent finding of an 832 nucleotide deletion
in ORF8, which appears to reduce the replicative fitness of the virus and leads to
attenuated phenotypes of SARS-CoV-2. The RBD of S protein in CoV isolated from
pangolin was almost identical (one amino acid difference) to that of SARS-CoV-2.
A comparison of the genomes suggests recombination between pangolin-CoV-like
viruses with the bat-CoV-RaTG13-like virus. All this suggests the potential of
pangolins to act as the intermediate host of SARS-CoV-2. Human-wildlife
interactions, which are increasing in the context of climate change, are further
considered high risk and responsible for the emergence of SARS-CoV. COVID-19
is also suspected of having a similar mode of origin. Hence, to prevent the
occurrence of another zoonotic spillover, exhaustive coordinated efforts are needed
to identify the high-risk pathogens harbored by wild animal populations, conducting
surveillance among the people who are susceptible to zoonotic spillover events, and
to improve the biosecurity measures associated with the wildlife trade. The
serological surveillance studies conducted in people living in proximity to bat caves
had earlier identified the serological confirmation of SARS related CoVs in humans.
People living at the wildlife-human interface, mainly in rural China, are regularly
exposed to SARS-related CoVs. Patients should be placed in separate rooms or
cohosted 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 at least 3 d and have two consecutive negative molecular
tests at 1 d sampling interval. CEPI has also funded Moderna to develop a vaccine
for COVID-19 in partnership with the Vaccine Research Center (VRC) of the
National Institute of Allergy and Infectious Diseases (NIAID), part of the National
Institutes of Health (NIH). By employing mRNA vaccine platform technology, a
vaccine candidate expressing SARS-CoV-2 spike protein is likely to go through
clinical testing in the coming months. On 16 March 2020, Jennifer Haller became
the first person outside China to receive an experimental vaccine, developed by
Moderna, against this pandemic virus. Moderna, along with China's Casino
Biologics, became the first research group to launch small clinical trials of vaccines
against COVID-19. Their study is evaluating the vaccine's safety and ability to
trigger immune responses. Scientists from all over the world are trying hard to
develop working vaccines with robust protective immunity against COVID-19.
Vaccine candidates, like mRNA-1273 SARS-CoV-2 vaccine, INO-4800 DNA
coronavirus vaccine, and adenovirus type 5 vector vaccine candidate (Ad5-nCoV),
are a few examples under phase I clinical trials, while self-amplifying RNA vaccine,
oral recombinant COVID 19 vaccine, BNT162, plant-based COVID-19 vaccine, and
li-Key peptide COVID-19 vaccine are 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. 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.
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. More recently, other advanced diagnostics have been designed and
developed for the detection of SARS-CoV-2. A reverse transcriptional loop-
mediated isothermal amplification (RT-LAMP), namely, iLACO, has been
developed for rapid and colorimetric detection of this. The global impact of this new
epidemic is yet uncertain.
Introduction:
The 2019 novel coronavirus (2019 nCoV) or the severe acute respiratory syndrome
corona virus 2 (SARS-CoV-2) as it is now called, is rapidly spreading from its origin
in Wuhan City of Hubei Province of China to the rest of the world. Till 05/03/2020
around 96,000 cases of coronavirus disease 2019 (COVID-19) and 3300 deaths have
been reported. India has reported 29 cases till date. Fortunately so far, children have
been infrequently affected with no deaths. But the future course of this virus is
unknown. This article gives a bird's eye view about viruses in nasal washes, saliva,
urine and faces for up to 8 days after infection, and a few naive ferrets with only
indirect contact were positive for viral RNA, suggest in airborne transmission". In
addition, transmission of the virus through the ocular surface and prolonged presence
of SARS-CoV-2 viral RNA in fiscal 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 Korea
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 ORF1b (including RdRp), N, E or S genes are commercially
available. The detection time ranges from several minutes to hours depending on the
technology. 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 samples. In addition,
viral nucleic acid was also found in samples from the intestinal tract or blood even
when respiratory samples were negative, 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 diagnosis. Other detection methods were therefore used to overcome this
problem. Chest CT was used to quickly identify a patient when the capacity of
molecular detection was overloaded in Wuhan. Presently, the main course of
treatment for severely affected SARS-CoV-2 patients admitted to hospitals includes
mechanical ventilation, intensive care unit (ICU) admittance, and symptomatic and
supportive therapies. Additionally, RNA synthesis inhibitors (lamivudine and
tenofovir disoproxil fumarate), remdesivir, neuraminidase inhibitors, peptide (EK1),
anti-inflammatory drugs, abidol, and Chinese traditional medicine (Lianhuaqingwen
and ShuFeng Jie Du capsules) could aid in COVID-19 treatment. However, further
clinical trials are being carried out concerning their safety and efficacy. It might
require months to a year to design and develop effective drugs, therapeutics, and
vaccines against COVID-19, with adequate evaluation and approval from regulatory
bodies and moving to the bulk production of many millions of doses at commercial
levels to meet the timely demand of mass populations across the globe. Continuous
efforts are also warranted to identify and assess viable drugs and immunotherapeutic
regimens that revealed proven potency in combating other viral agents similar to
SARS-CoV-2. 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.
The SARS outbreak reported in 2002 to 2003 had 8,098 confirmed cases with 774
total deaths (9.6%).The outbreak severely affected the Asia Pacific region,
especially mainland China. 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. This can
fail the public health system, resulting in a pandemic. 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%. 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. The newly emerged SARS-CoV-2 is a group 2B coronavirus. The
genome sequences of SARS CoV-2 obtained from patients share 79.5% sequence
similarity to the sequence of SARS-CoV. As of 13 May 2020, a total of 4,170,424
confirmed cases of COVID-19 (with 287,399 deaths) have been reported in more
than 210 affected countries worldwide (WHO Situation Report 114) and other
SARSr-CoVs. Using sequences of five conserved replicative domains in pplab (3C-
like protease (3CLpro), norovirus RNA-dependent RNA polymerase (RdRp)-
associated nucleotidyltransferase (NIRAN), RdRp, zinc-binding domain (ZBD) and
HEL1), the Coronaviridae Study Group of the International Committee on
Taxonomy of Viruses estimated the pairwise patristic distances between SARS-
CoV-2 and known coronaviruses, and assigned SARS-CoV-2 to the existing species
SARS-CoV. Although phylogeny nautically related, SARS-CoV-2 is distinct from
all other coronaviruses from bats and pangolins in this species. The SARS-CoV-2 S
protein has a full size of 1,273 amino acids, longer than that of SARS-CoV (1,255
amino acids) and known bat SARSr-CoVs (1,245-1,269 amino acids). It is distinct
from the S proteins of most members in the subgenus.
VIROLOGY:
Coronaviruses, a family of viruses within the noroviruses superfamily, are further
classified according to their genera, alpha-, beta-, gamma and delta coronaviruses
(a-, B-, y- and ō-). Among those, alpha and beta species are capable of contaminating
only mammals, whereas the other two genera can infect birds and could also infect
mammals. Two of these genera belong to human coronaviruses (HCOVs): a-
coronaviruses, which comprise human coronavirus 229E (hcov229E) and human
coronavirus NL63 (hcovNL63), and B coronaviruses, which are human coronavirus
HKU1, human coronavirus OC43, MERS-COV (known as Middle East respiratory
syndrome coronavirus) and SARS-CoV (referred to as severe acute respiratory
syndrome coronavirus), the severe acute respiratory syndrome CoV-2 (SARS-COV-
2) is now named novel COVID-19 (coronavirus disease 2019). Genome sequencing
and phylogenetic research revealed that the COVID-19-causing coronavirus is a
beta-coronavirus that belongs to the same subtypes as SARS virus, but still exists in
a variant group. These possess benefits of easy accessibility and recognized
pharmacokinetic and pharmacodynamics activities, stability, doses, and side effects.
Repurposed drugs have been studied for treating CoV infections, like
lopinavir/ritonavir, and interferon-1ẞ revealed in vitro anti-MERS-CoV action. The
in vivo experiment carried out in the nonhuman primate model of common
marmosets treated with lopinavir/ritonavir and interferon beta showed superior
protective results in treated animals than in the untreated ones. A combination of
these drugs is being evaluated to treat MERS in humans (MIRACLE trial). These
two protease inhibitors (lopinavir and ritonavir), in combination with ribavirin, gave
encouraging clinical outcomes in SARS patients, suggesting their therapeutic values.
However, in the current scenario, due to the lack of specific therapeutic agents
against SARS CoV-2, hospitalized patients confirmed for the disease are given
supportive care, like oxygen and fluid therapy, along with antibiotic therapy for
managing secondary bacterial infections. Patients with novel coronavirus or
COVID-19 pneumonia who are mechanically ventilated often require sedatives,
analgesics and even muscle. At the beginning, China experienced the majority of the
burden associated with COVID-19 in the form of disease morbidity and mortality,
but over time the COVID-19 menace moved to Europe, particularly Italy and Spain,
and now the United States has the highest number of confirmed cases such instance
was in 2002-2003 when a new coronavirus of the ẞ genera and with origin in bats
crossed over to humans via the intermediary host of palm civet cats in the
Guangdong province of China. This virus, designated as severe acute respiratory
syndrome coronavirus affected 8422 people mostly in China and Hong Kong and
caused 916 deaths (mortality rate 11%) before being contained. Almost a decade
later in 2012, the Middle East respiratory syndrome coronavirus (MERS-CoV), also
of bat origin, emerged in Saudi Arabia with dromedary camels as the intermediate
host and affected 2494 people and caused 858 deaths (fatality rate 34%).
Origin and Spread of COVID-19:
In December 2019, adults in Wuhan, capital city of Hubei province and a Middle-
aged and elderly patients with primary chronic diseases, especially high blood
pressure and diabetes, were found to be more susceptible to respiratory failure and,
therefore, had poorer prognoses. Providing respiratory support at early stages
improved the disease prognosis and facilitated recovery. The ARDS in COVID-19
is due to the occurrence of cytokine storms that results in exaggerated immune
response, immune regulatory network imbalance, and, finally, multiple-organ
failure. In addition to the exaggerated inflammatory response seen in patients with
COVID-19 pneumonia, the bile duct epithelial cell derived hepatocytes upregulate
ACE2 expression in liver tissue by compensatory proliferation that might result in
hepatic tissue injury.
CORONAVIRUSES IN ANIMALS AND ZOONOTIC LINKS A BRIEF:
Coronavirus can cause disease in several species of domestic and wild animals, as
well as humans. The different animal species that are infected with CoV include
horses, camels, cattle, swine, dogs, cats, rodents, birds, ferrets, minks, bats, rabbits,
snakes, and various other wild animals. 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 RBD-containing recombinant proteins or recombinant
vectors that encode RBD. 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 in 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. Hence, the possibility of SARS-
CoV-specific neutralizing antibodies providing cross-protection to COVID-19
might be lower.
Animal Models and Cell Cultures:
For evaluating the potential of vaccines and therapeutics against CoVs, including
SARS-CoV, MERS-CoVs, and the presently emerging SARS CoV-2, suitable
animal models that can mimic the clinical disease are needed. Various animal
models were assessed for SARS- and MERS CoVs, such as mice, guinea pigs,
golden Syrian hamsters, ferrets, rabbits, nonhuman primates like rhesus macaques
and marmosets, and cats. The specificity of the virus to hACE2 (receptor of SARS-
CoV) was found to be a significant barrier in developing animal models.
Consequently, a SARS-CoV transgenic mouse model has been developed by
inserting the hACE2 gene into the mouse genome. The inability of MERS-CoV to
replicate in the respiratory tracts of animals (mice, hamsters, and ferrets) is another
limiting factor. However, with genetic engineering, a 288-330+ MERS-CoV
genetically modified mouse model was developed and now is in use for the
assessment of novel drugs and vaccines against MERS-CoV. In the past, small
animals (mice or hamsters) have been targeted for being closer to a humanized
structure, such as mouse DPP4 altered with human DPP4 (hDPP4), this emerging
virus will establish a niche in humans and coexist with us for a long time. Before
clinically approved vaccines are widely available, there is no better way to protect
us from SARS-CoV-2 than personal preventive behaviors 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. At present, we are not in a position to effectively treat COVID-
19, since neither approved vaccines nor specific antiviral drugs for treating human
CoV infections are available. Most nations are currently making efforts to prevent
the further spreading of this potentially deadly virus by implementing preventive and
control strategies. In domestic animals, infections with CoVs are associated with a
broad spectrum of pathological conditions. Apart from infectious bronchitis virus,
canine respiratory CoV, and mouse hepatitis virus, CoVs are predominantly
associated with gastrointestinal diseases. The emergence of novel Covs may have
become possible because of multiple CoVs being maintained in their natural host,
which could have favored the probability of genetic recombination. High genetic
diversity and the ability to infect multiple host species are a result of high-frequency
mutations in CoVs, which occur due to the instability of RNA-dependent RNA
polymerases along with higher rates of homologous RNA recombination.
Identifying the origin of SARS-CoV-2 and the pathogen's evolution will be helpful
for disease surveillance, development of 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. Detailed guidelines for critical care
management for COVID-19 have been published by the WHO. 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.
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 vision assembly, and enhances the transcription efficiency of the
virus. It contains three highly conserved and distinct domains, namely, an NTD, an
RNA-binding domain or a linker region (LKR), and a CTD. The NTD binds with
the 3' end of the viral genome, perhaps via electrostatic interactions, and is highly
diverged both in length and sequence. The charged LKR is serine and arginine rich
and is also known as the SR (serine and arginine) domain. The LKR is capable of
direct interaction with in vitro RNA interaction and is responsible for cell signaling.
It also modulates the antiviral response of the host by working as an antagonist for
interferon (IFN) and RNA interference. 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). Hence, as a cautionary
approach, it is better to recommend the use of NSAIDS as the first-line option for
managing COVID-19 symptoms. The use of corticosteroids in COVID-19 patients
is still a matter of controversy and requires further systematic clinical studies. The
guidelines that were put forward to manage critically ill adults suggest the use of
systemic corticosteroids in mechanically ventilated adults with ARDS. The
generalized use of corticosteroids is not indicated in COVID-19, since there are
some concerns associated with the use of corticosteroids in viral pneumonia. Stem
cell therapy using mesenchymal stem cells (MSCs) is another hopeful strategy that
can be used in clinical cases of COVID-19 owing to its potential immunomodulatory
capacity. It may have a beneficial role in attenuating the cytokine storm that is
observed in severe cases of SARS-CoV-2 infection, thereby reducing mortality.
Among the different types of MSCs, expanded umbilical cord MSCs can be
considered a potential therapeutic agent that requires further validation for managing
critically ill COVID-19 patients. 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. Among the CoV
genera, Alpha coronavirus and Beta coronavirus infect mammals, while Gamma
coronavirus and Delta coronavirus mainly infect birds, fishes, and, sometimes,
mammals. Several novel coronaviruses that come under the genus Delta coronavirus
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 HKU15). Transmissible
gastroenteritis virus (TGEV), porcine epidemic diarrhea virus (PEDV), and porcine
hem agglutinating 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 themselves while examining such patients and practice hand
hygiene frequently. Suspected cases should be referred to government designated
centers 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.
RECOMBINANT SUBUNIT VACCINE:
Clover Biopharmaceuticals is producing a recombinant subunit vaccine based on the
trimeric S-protein of COVID-19. The oral recombinant vaccine is being expanded
by Vaxart in tablet formulation, using its proprietary oral vaccine platform.
CLINICAL MANAGEMENT AND TREATMENT:
In severe COVID-19 cases, treatment should be given to support vital organ
functions. People who think they may have been exposed to COVID-19 should
contact their healthcare provider immediately. Healthcare personnel should care for
patients in an Airborne Infection Isolation Room (AIIR). Precautions must be taken
by the healthcare professional, such as contact precautions and airborne precautions
with eye protection. Individuals with a mild clinical presentation may not require
primary hospitalization. Close monitoring is needed for the persons infected with
COVID-19. Elderly patients and those with prevailing chronic medical conditions
such as Future explorative research needs to be conducted with regard to the fecal-
oral transmission of SARS-CoV-2, along with focusing on environmental
investigations to find out if this virus could stay viable in situations and atmospheres
facilitating such potent routes of transmission. The correlation of fecal
concentrations of viral RNA with disease severity needs to be determined, along
with assessing the gastrointestinal symptoms and the possibility of fecal SARS-
CoV-2 RNA detection during the COVID-19 incubation period or convalescence
phases of the disease. The lower respiratory tract sampling techniques, like Broncho
alveolar lavage fluid aspirate, are considered the ideal clinical materials, rather than
the throat swab, due to their higher positive rate on the nucleic acid test. The
diagnosis of COVID 19 can be made by using upper-respiratory-tract specimens
collected using nasopharyngeal and oropharyngeal swabs. However, these
techniques are associated with unnecessary risks to health care workers due to close
contact with patients. Similarly, a single patient with a high viral load was reported
to contaminate an entire endoscopy room by shedding the virus, which may remain
viable for at 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 organ support. 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 in MERS-COV patients.
EARLY SUPPORTIVE THERAPY 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. Immediate therapy of add-on oxygen must
be started for patients with severe acute respiratory infection (SARI) and respiratory
infections clinically or through routine lab tests. Therefore travel history becomes
important. However, as the epidemic spreads, the travel history will become
irrelevant.
Treatment:
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. To assess the
genetic variation of different SARS CoV-2 strains, the 2019 Novel Coronavirus
Resource of China National Center for Bio information aligned 77,801 genome
sequences of SARS-CoV-2 detected glob ally and identified a total of 15,018
mutations, including 14,824 single-nucleotide polymorphisms (BIGD). 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 titers 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 administration of the recombinant
adenovirus-based vaccine in BALB/c mice was found to induce long lasting
neutralizing immunity against MERS spike pseudo typed virus, characterized by the
induction of systemic IgG, secretory IgA, and lung-resident memory T-cell
responses. Immune informatics methods have been employed for the genome-wide
screening of potential vaccine targets among the different immunogens of MERS-
CoV. The N protein and the potential B-cell epitopes of MERS CoV E protein have
been suggested as immune protective targets inducing both T-cell and neutralizing
antibody responses. The collaborative effort of the researchers of Rocky Mountain
Laboratories and Oxford University is designing a chimpanzee adenovirus-vectored
vaccine to counter COVID-19. The Coalition for Epidemic Preparedness
Innovations (CEPI) has initiated three programs to design SARS-CoV-2 vaccines.
CEPI has a collaborative project with Inovio for designing a MERS-CoV DNA
vaccine that could potentiate effective immunity. CEPI and the University of
Queensland are designing a molecular clamp vaccine platform for MERS-CoV and
other pathogens, which could assist in the easier identification of antigens by the
immune system. The Chinese government is encouraging people to feel they can
return to normalcy. However, this could be a risk, as it has been mentioned in
advisories that people should avoid contact with live-dead animals as much as
possible, as SARS-CoV-2 has shown zoonotic spillover. Additionally, we cannot
rule out the possibility of new mutations in the same virus being closely related to
contact with both animals and humans at the market. In January 2020, China
imposed a temporary ban on the sale of live dead animals in wet markets. However,
now hundreds of such wet markets have been reopened without optimizing standard
food safety and sanitation practices. With China being the most populated country
in the world and due to its domestic and international food exportation policies, the
whole world is now facing the menace of COVID-19, including China itself. Wet
markets of live-dead animals do not maintain strict food hygienic practices. Fresh
blood splashes are present everywhere, on the floor and tabletops, and such food
customs could encourage many pathogens to adapt, mutate, and jump the species
barrier. As a result, the whole world is suffering from novel SARS-CoV-2. Some
therapeutic options for treating COVID-19 showed efficacy in in vitro studies;
however, to date, these treatments have not undergone any randomized animal or
human clinical trials, which limit their practical applicability in the current
pandemic. The present comprehensive review describes the various features of
SARS-CoV-2/COVID-19 causing the current disease outbreaks and advances in
diagnosis and developing vaccines and therapeutics. It also provides a brief
comparison with the earlier SARS and MERS CoVs, the veterinary perspective of
CoVs and this emerging novel pathogen, and an evaluation of the zoonotic potential
of similar Covs to provide feasible One Health strategies for the management of this
fatal virus.
THE VIRUS (SARS-CoV-2):
Coronaviruses are positive-sense RNA viruses having an extensive and promiscuous
range of natural hosts and affect multiple systems. Coronaviruses can cause clinical
diseases in humans that may extend from the common cold to more severe
respiratory diseases like SARS and MERS. The recently emerging SARS-CoV-2 has
wrought havoc in China and caused a pandemic situation in the worldwide
population leading to 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. In the case series of 99 hospitalized patients with COVID-19 infection from
Wuhan, oxygen was given to 76%, noninvasive ventilation in 13%, mechanical
ventilation in 4%, extracorporeal membrane oxygenation (ECMO) in 3%,
continuous renal replacement therapy (CRRT) in 9%, antibiotics in 71%, antifungals
in 15%, glucocorticoids in 19% and intravenous immunoglobulin therapy in 27%.
Antiviral therapy consisting of oseltamivir, ganciclovir and lopinavir ritonavir was
given to 75% of the patients.
Therapeutics and Drugs:
There is no currently licensed specific antiviral treatment for MERS- and SARS-
CoV infections, and the main focus in clinical settings remains on lessening clinical
signs and providing supportive care. Effective drugs to manage COVID 19 patients
include remdesivir, lopinavir/ritonavir alone or in a blend with interferon beta,
convalescent plasma, and monoclonal antibodies (MAbs); however, efficacy and
safety issues of these drugs require additional clinical trials. A controlled trial of
ritonavir-boosted lopinavir and interferon alpha 2b treatment was performed on
COVID-19 hospitalized patients (ChiCTR2000029308). In addition, the use of
hydroxychloroquine and tocilizumab for their potential role in modulating
inflammatory responses in the lungs and antiviral effect has been proposed and
discussed in many research articles. Still, no fool-proof clinical trials have been
published. Recently, a clinical trial conducted on adult patients suffering from severe
COVID-19 revealed no benefit of lopinavir-ritonavir treatment over standard care.
The efforts to control SARS-CoV-2 infection utilize defined strategies as followed
against MERS and SARS, along with adopting and strengthening.
Origin and Spread of COVID-19:
In December 2019, adults in Wuhan, capital city of Hubei province and a major
transportation hub of China started presenting to local hospitals with severe
pneumonia of unknown cause. Many of the initial cases had a common exposure to
the Huanan wholesale seafood market that also traded live animals. The surveillance
system (put into place after the SARS outbreak) was activated and respiratory
samples of patients were sent to reference labs for etiologic investigations. On
December 31st 2019, China notified the outbreak to the World Health Organization
and on 1st January the Huanan sea food market was closed. On 7th January the virus
was identified as a coronavirus that had >95% homology with the bat. The most
common symptoms associated with COVID-19 are fever, cough, dyspnea,
expectoration, headache, and myalgia or fatigue. In contrast, less common signs at
the time of hospital admission include diarrhea, hemoptysis, and shortness of breath.
Recently, individuals with asymptomatic infections were also suspected of
transmitting infections, which further ads to the complexity of disease transmission
dynamics in COVID-19 infections. Such efficient responses require in-depth
knowledge regarding the virus. Which currently is a novel agent; consequently,
further studies are required. Comparing the genome of SARS-CoV-2 with that of the
closely related SARS/SARS-like CoV revealed that the sequence coding for the
spike protein, with a total length of 1,273 amino acids, showed 27 amino acid
substitutions. Six of these substitutions are in the region of the receptor-binding
domain (RBD), and another six substitutions are in the underpinning subdomain
(SD). Phylogenetic analyses have revealed that SARS-CoV-2 is closely related (88%
similarity) to two SARS-like CoVs derived from bat SARS-like CoVs (bat-SL
CoVZC45 and bat-SL-CoVZXC21).
Therapeutics and Drugs:
There is no currently licensed specific antiviral treatment for MERS- and SARS-
CoV infections, and the main focus in clinical settings remains on lessening clinical
signs and providing supportive care. Effective drugs to manage COVID 19 patients
include remdesivir, lopinavir/ritonavir alone or in a blend with interferon beta,
convalescent plasma, and monoclonal antibodies (MAbs); however, efficacy and
safety issues of these drugs require additional clinical trials. A controlled trial of
ritonavir-boosted lopinavir and interferon alpha 2b treatment was performed on
COVID-19 hospitalized patients (ChiCTR2000029308). In addition, the use of
hydroxychloroquine and tocilizumab for their potential role in modulating
inflammatory responses in the lungs and antiviral effect has been proposed and
discussed in many research articles. Still, no fool-proof clinical trials have been
published. Recently, a clinical trial conducted on adult patients suffering from severe
COVID-19 revealed no benefit of lopinavir-ritonavir treatment over standard care.
The efforts to control SARS-CoV-2 infection utilize defined strategies as followed
against MERS and SARS, along with adopting and strengthening.
Origin and Spread of COVID-19:
In December 2019, adults in Wuhan, capital city of Hubei province and a major
transportation hub of China started presenting to local hospitals with severe
pneumonia of unknown cause. Many of the initial cases had a common exposure to
the Huanan wholesale seafood market that also traded live animals. The surveillance
system (put into place after the SARS outbreak) was activated and respiratory
samples of patients were sent to reference labs for etiologic investigations. On
December 31st 2019, China notified the outbreak to the World Health Organization
and on 1st January the Huanan sea food market was closed. On 7th January the virus
was identified as a coronavirus that had >95% homology with the bat new targeted
drugs, and prevention of further epidemics. The most common symptoms associated
with COVID-19 are fever, cough, dyspnea, expectoration, headache, and myalgia or
fatigue. In contrast, less common signs at the time of hospital admission include
diarrhea, hemoptysis, and shortness of breath. Recently, individuals with
asymptomatic infections were also suspected of transmitting infections, which
further ads to the complexity of disease transmission dynamics in COVID-19
infections. Such efficient responses require in-depth knowledge regarding the virus,
which currently is a novel agent; consequently, further studies are required.
Comparing the genome of SARS-CoV-2 with that of the closely related
SARS/SARS-like CoV revealed that the sequence coding for the spike protein, with
a total length of 1,273 amino acids, showed 27 amino acid substitutions. Six of these
substitutions are in the region of the receptor-binding domain (RBD), and another
six substitutions are in the underpinning subdomain (SD). Phylogenetic analyses
have revealed that SARS-CoV-2 is closely related (88% similarity) to two SARS-
like CoVs derived from bat SARS-like CoVs (bat-SL CoVZC45 and bat-SL-
COVZXC21). 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. The substantial importation of
COVID-19 presymptomatic 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 of COVID-19.
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. Although nearly 30 cruise ships from different countries have been
found harboring COVID-19 infection, the major cruise ships that were involved in
the COVID-19 outbreaks are the Diamond Princess, Grand Princess, Celebrity
Apex, and Ruby Princess.
Specimen collection and storage:
A Nasopharyngeal and oropharyngeal swab should be collected using Dacron or
polyester flocked swabs. It should be transported to the laboratory at a temperature
of 4°C and stored in the laboratory between 4 and -70°C on the basis of the number
of days and, in order to increase the viral load, both nasopharyngeal and
oropharyngeal swabs should be placed in the same tube. Broncho alveolar lavage
and nasopharyngeal aspirate should be collected in a sterile container and
transported similarly to the laboratory by maintain a temperature of 4°C. Sputum
samples, especially from the lower respiratory tract, should be collected with the
help of a sterile container and stored, whereas tissue from a biopsy or autopsy should
be collected using a sterile container along with saline. However, both should be
stored in the laboratory at a temperature that ranges between 4 and -70°C. Whole
blood for detecting the antigen, particularly in the first week of illness, should be
collected in a collecting tube and stored in the laboratory between 4 and -70°C. Urine
samples must also be collected using a sterile container and stored maravią;
prompjeŭ nurince ampiadidly was resulted in the epidemic strain. Transmission can
also occur directly from the reservoir host to humans without RBD adaptations. The
bat coronavirus that is currently in circulation maintains specific "poised" spike
proteins that facilitate human infection without the requirement of any mutations or
adaptations. Altogether, different species of bats carry a massive number of
coronaviruses around the world. The high plasticity in receptor usage, along with the
feasibility of adaptive mutation and recombination, may result in frequent
interspecies transmission of coronavirus from bats to animals and humans. The
pathogenesis of most bat coronaviruses is unknown, as most of these viruses are not
isolated and studied. Hedgehog coronavirus HKU31, a Beta coronavirus, has been
identified from amur hedgehogs in China. Studies show that hedgehogs are the
reservoir of Beta coronavirus, and there is evidence of recombination. The current
scientific evidence available on MERS infection suggests that the significant
reservoir host, as well as the animal source of MERS infection in humans, is the
dromedary camels. The infected dromedary camels may not show any visible signs
of infection, making it challenging to possible origin of SARS-CoV-Z and the brat
mode of disease transmission are not yet identified. Analysis of the initial cluster of
infections suggests that the infected individuals had a common exposure point, a
seafood market in Wuhan, Hubei Province, China. The restaurants of this market are
well-known for providing different types of wild animals for human consumption.
The Huanan South China Seafood Market also sells live animals, such as poultry,
bats, snakes, and marmots. This might be the point where zoonotic (animal-to
human) transmission occurred. Although SARS-CoV-2 is alleged to have originated
from an animal host (zoonotic origin) with further human-to human transmission,
the likelihood of foodborne transmission should be ruled out with further
investigations, since it is a latent possibility. Additionally, other potential and
expected routes would be associated with transmission, as in other respiratory
viruses, by direct contact, such as shaking contaminated hands, or by direct contact
with contaminated surfaces. Still, whether blood transfusion and organ
transplantation, as well as Trans placental and perinatal routes, are possible routes
for SARS-CoV-2 transmission needs to be determined.
Epidemiology and Pathogenesis:
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. 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. 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. These infected droplets can spread 1-2 m and deposit.
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. 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 (RT
PCR). 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. It is also recommended that the
suspected patients be tested for the other respiratory pathogens by performing the
routine laboratory investigation per the local guidelines, mainly to differentiate from
other viruses that include influenza virus, parainfluenza virus, adenovirus,
respiratory syncytial virus, and rhinovirus, human. 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.
nsps and Accessory Proteins:
Besides the important structural proteins, the SARS-CoV-2 genome contains 15
nsps, nspl to nsp10 and nsp12 to nsp16, and 8 accessory proteins (3a, 3b, p6, 7a, 7b,
8b, 9b, and ORF14). All these proteins play a specific role in viral replication. Unlike
the accessory proteins of SARS-CoV, SARS-CoV-2 does not contain 8a protein and
has a longer 8b and shorter 3b protein. 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. Therapeutics and drug regimens
to counter emerging viruses. Several attempts are being made to design and develop
vaccines for CoV infection, mostly by targeting the spike glycoprotein.
Nevertheless, owing to extensive diversity in antigenic variants, cross-protection
rendered by the vaccines is significantly limited, even within the strains of a
phylogenetic sub cluster. Due to the lack of effective antiviral therapy and vaccines
in the present scenario, we need to depend solely on implementing effective
infection control measures to lessen the risk of possible nosocomial transmission.
Recently, the receptor for SARS-CoV-2 was established as the human angiotensin-
converting enzyme 2 (hACE2), and the virus was found to enter the host cell mainly
through endocytosis. It was also found that the major components that have a critical
role in viral entry include PIKfyve, TPC2, and cathepsin L. These findings are
critical, since the components described above might act as candidates for vaccines
or therapeutic drugs against SARS CoV-2. The majority of the treatment options and
strategies that are being evaluated for SARS-CoV-2 (COVID-19) have been taken
from our previous experiences in treating SARS-CoV, MERS-CoV, and other
emerging viral diseases. 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-CoV.
Coronavirus S protein is a large, multifunctional class I viral transmembrane protein.
The size of this abundant S protein varies from 1,160 amino acids (IBV, infectious
bronchitis virus, in poultry) to 1,400 amino acids (FCOV, feline coronavirus). It lies
in a trimer on the vision surface, giving the vision a corona or crown-like appearance.
Functionally it is required for the entry of the infectious vision particles into the cell
through interaction with various host cellular receptors. Furthermore, it acts as a
critical factor for tissue tropism and the determination of host range. Notably, S
protein is one of the vital immunodominant proteins of CoVs capable of inducing
host immune responses. The codomains in all CoVs S proteins have similar domain
organizations, divided into two subunits, S1 and S2. The first one, S1, helps in host
receptor binding, while the second one, S2, accounts for fusion. The former (S1) is
further divided into two subdomains, namely, the N-terminal domain (NTD) and C-
terminal domain (CTD). Both of these subdomains act as receptor-binding domains,
interacting efficiently with various host receptors. The S1 CTD contains the
receptor-binding motif (RBM). In each coronavirus spike protein, the trimeric S1
locates itself on top of the trimeric S2. In the case series of children discussed earlier,
all children recovered with basic treatment and did not need intensive care. There is
anecdotal experience with use of remdeswir, a broad spectrum anti RNA drug
developed for Ebola in management of COVID-19. More evidence is needed before
these drugs are recommended. Other drugs proposed for therapy are arborol (an
antiviral drug available in Russia and China), intravenous immunoglobulin,
interferons, chloroquine and plasma of patients recovered from COVID-19.
Additionally, recommendations about using traditional Chinese herbs find place in
the Chinese guideline. Among the evaluated compounds, 4-(cyclopent1-en-3-
ylamino)-5-[2-(4iodophenyl) hydrazinyl]-4H-1, 2, 4-triazole-3-thiol and4-
(cyclopent-1-en-3-ylamino)-5-[2-(4chlorophenyl) hydrazinyl]-4H-1, 2, 4-triazole-
3-thiol were found to be the most potent. These compounds were used for in silico
studies, and molecular docking was accomplished into the active binding site of
MERS-CoV helicase nsp13. Further studies are required for evaluating the
therapeutic potential of these newly identified compounds in the management of
COVID-19 infection. Passive Immunization/Antibody Therapy/MAb Monoclonal
antibodies (MAbs) may be helpful in the intervention of disease in CoV-exposed
individuals. Patients recovering from SARS showed robust neutralizing antibodies
against this CoV infection. A set of MAbs aimed at the MERS CoV S protein-
specific domains, comprising six specific epitope groups interacting with receptor
binding, membrane fusion, and sialic acid-binding sites, make up crucial entry tasks
of S protein. Passive immunization employing weaker and strongly neutralizing
antibodies provided considerable protection in mice against a MERS. The
exploration of fully human antibodies (human single-chain antibodies; HuscFvs) or
humanized Nano bodies (single-domain antibodies; sdAb, VH/VHH) could aid in
blocking virus replication, as these agents can traverse the virus infected cell
membranes (trans bodies) and can interfere with the biological characteristics of the
replicating virus proteins. Such examples include Trans bodies to the influenza virus,
hepatitis C virus, Ebola virus, and dengue virus. Producing similar Trans bodies
against intracellular proteins of coronaviruses, such as papain-like proteases
(PLpro), cysteine-like protease (3CLpro), or other nsps, which are essential for
replication and transcription of the virus, might formulate a practical move forward
for a safer and potent passive immunization approach for virus-exposed persons and
rendering therapy to infected patients. In a case study on five grimly sick patients
having symptoms of severe pneumonia due to COVID-19, convalescent plasma
administration was found to be helpful in patients recovering successfully. The
convalescent plasma containing a SARS-CoV-2-specific ELISA (serum) antibody
titer higher than 1:1,000 and neutralizing antibody titer more significant than 40 was
collected from the recovered patients and used for plasma transfusion RBD,
indicating its potential as a therapeutic agent in the management of COVID-19. It
can be used alone or in combination with other effective neutralizing antibodies for
the treatment and prevention of COVID-19. Furthermore, SARS CoV-specific
neutralizing antibodies, like m396 and CR3014, failed to bind the S protein of
SARS-CoV 2, indicating that a particular level of similarity is mandatory between
the RBDS of SARS-CoV and SARS-CoV-2 for the cross-reactivity to occur. Further
assessment is necessary before confirming the effectiveness of such combination
therapy. In addition, to prevent further community and nosocomial spread of
COVID-19, the post procedure risk management program should not be neglected.
Development of broad-spectrum inhibitors against the human corona viral pathogens
will help to facilitate clinical trials on the effectiveness of such inhibitors against
endemic and emerging coronaviruses. A promising animal study revealed the
protective effect of passive immunotherapy with immune serum from MERS
immune camels on mice infected with MERS-CoV. Passive immunotherapy using
convalescent plasma is another strategy that can be used for treating COVID-19-
infected, critically ill patients. Cases continued to increase exponentially and
modelling studies reported an epidemic doubling time of 1.8 d. 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. As
of 05/03/2020 96,000 cases worldwide (80,000 in China) and 87 other countries and
1 international conveyance (696, in the cruise ship Diamond Princess parked off the
coast of Japan) have been reported. 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% are in critical
condition. The COVID-19 outbreak has also been associated with severe economic
impacts globally due to the sudden interruption of global trade and supply chains
that forced multinational companies to make decisions that led to significant
economic losses. The recent increase in the number of confirmed critically ill
patients with COVID-19 has already surpassed the intensive care supplies, limiting
intensive care services to only a small portion of critically ill patients. This might
also have contributed to the increased case fatality rate observed in the COVID-19
outbreak.
Viewpoint on SARS-CoV-2 Transmission, Spread, and Emergence:
The novel coronavirus was identified within 1 month (28 days) of the outbreak. This
is impressively fast compared to the time taken to identify SARS CoV reported in
Foshan, Guangdong Province, China (125 days). Immediately after the confirmation
of viral etiology, the Chinese virologists rapidly released the genomic sequence of
SARS-CoV-2, which played a crucial role in controlling the spread of this newly
emerged novel coronavirus to other parts of the world. The number of confirmed
cases suddenly increased, with thousands of new cases diagnosed daily during late
January. On 30 January, the WHO declared the novel coronavirus outbreak a public
health emergency of international concern". On 11 February, the International
Committee on Taxonomy of Viruses named the novel coronavirus 'SARS-CoV-2,
and the WHO named the disease 'COVID-19'. The outbreak of COVID-19 in China
reached an epidemic peak in February. According to the National Health
Commission of China, the total number of cases continued to rise sharply in early
February at an average rate of more than 3,000 newly confirmed cases per day. To
control COVID-19, China implemented unprecedentedly strict public health
measures. The city of Wuhan was shut down on 23 January, and all travel and
transportation connecting the city was blocked. In the following couple of weeks, all
outdoor activities and gatherings were restricted, and public facilities were dosed in
most cities as well as in countryside"". Owing to these measures, the daily number
of new cases in China started to decrease steadily. However, despite the declining
trend in China, the international spread of COVID-19 accelerated from late
February. Large clusters of infection have been reported from an increasing number
of countries. The high transmission efficiency of SARS-CoV-2 and the abundance
of international travel enabled rapid worldwide spread of COVID-19. On 11 March
2020, the WHO officially characterized the global COVID-19 outbreak as a
pandemic". Since March, while COVID-19 in China has become effectively
controlled, the case numbers in Europe, the USA and other regions have jumped
sharply. According to the COVID-19 dash board of the Center for System Science
and Engineering at Johns Hopkins University, as of 11 August 2020. Susceptible
individuals. Hence, hand hygiene is equally as important as the use of appropriate
PPE, like face masks, to break the transmission cycle of the virus; both hand hygiene
and face masks help to lessen the risk of COVID-19 transmission. Medical staff are
in the group of individuals most at risk of getting COVID-19 infection. This is
because they are exposed directly to infected patients. Hence, proper training must
be given to all hospital staff on methods of prevention and protection so that they
become competent enough to protect themselves and others from this deadly disease.
As a preventive measure, health care workers caring for infected patients should take
extreme precautions against both contact and airborne transmission. They should use
PPE such as face masks (N95 or FFP3), eye protection (goggles), gowns, and gloves
to nullify the risk of infection. The human-to-human transmission reported in SARS-
CoV-2 infection occurs mainly through droplet or direct contact. Due to this finding,
frontline health care workers should follow stringent infection control and
preventive measures, such as the use of PPE, to prevent infection. The mental health
of the medical/health workers who are involved in the COVID-19 outbreak is of
great. Interestingly, disease in patients outside Hubei province has been reported to
be milder than those from Wuhan. Similarly, the severity and case fatality rate in
patients outside China has been reported to be milder. 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 ACE2 receptors on the respiratory mucosa. Disease in neonates,
infants and children has been also reported to be significantly milder than their adult
counterparts. 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. Wearing a facemask and practicing hand hygiene before feeding the baby.
In addition, it is advisable that breast pumps are cleaned properly after each use and,
if possible, a healthy individual is available to feed the expressed breast milk to the
infant.
Children and elderly population:
On the basis of the available reports, COVID-19 among children accounted for 1-
5% of the confirmed cases, and this population does not seem to be at higher risk for
the disease than adults. There is no difference in the COVID-19 symptoms between
adults and children. However, the available evidence indicated that children
diagnosed with COVID-19 have milder symptoms than the adults, with a low
mortality rate. On the contrary, older people who are above the age of 65 years are
at higher risk for a severe course of disease. In the United Stated, approximately 31-
59% of those with confirmed COVID-19 between the ages of 65 and 84 years old
required hospitalization, 11-31% of them required admission to the intensive care
unit, and 4-11% died. Respiratory infection (SARI) and respiratory distress, shock
or hypoxemia. 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).
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.
Generally, such patients give way to their primary illness to secondary complications
like sepsis or multi organ system failure. The pathogenesis of SARS-CoV-2
infection in humans manifests itself as mild symptoms to severe respiratory failure.
On binding to epithelial cells in the respiratory tract, SARS-CoV-2 starts replicating
and migrating down to the airways and enters alveolar epithelial cells in the lungs.
The rapid replication of SARS-CoV-2 in the lungs may trigger a strong immune
response. Cytokine storm syndrome causes acute res purgatory distress syndrome
and respiratory failure, which is considered the main cause of death in patients with
COVID-19. Patients of older age (>60 years) and with serious pre-existing diseases
have a greater risk of developing acute respiratory distress syndrome and death.
Multiple organ failure has also been reported in some COVID-19 cases.
Histopathological changes in patients with COVID-19 occur mainly in the lungs.
Histopathology analyses showed bilateral diffused alveolar damage, hyaline
membrane formation, desquamation of pneumocystis and fibrin deposits in lungs of
patients with severe COVID-19. Exudative inflammation was also shown in some
cases. Immunohistochemistry assays detected SARS-CoV-2 antigen in the upper
airway, bronchiolar epithelium and submucosal gland epithelium, as well as in type
I and type II pneumocystis, alveolar macrophages and hyaline membranes in the
lungs. Animal models used for studying SARS-CoV-2 infection pathogenesis
include non-human primates (rhesus macaques, cynomolgus monkeys, marmosets
and African green monkeys), mice (wild-type mice (with mouse-adapted virus) and
human ACE2-transgenic or human ACE2-knock-in mice), ferrets and golden
hamsters. In non-human primate animal models, most species display clinical
features similar to those of patients with COVID-19, including virus shedding, virus
replication and host responses to SARS-CoV-2 infection, For example, in the rhesus
macaque model, high viral loads were detected in the upper another clinical trials in
different phases are still ongoing elsewhere. Immunomodulatory agents. SARS-
CoV-2 triggers a strong immune response which may cause cytokine storm
syndrome. Thus, immunomodulatory agents that inhibit the excessive inflammatory
response may be a potential adjunctive therapy for COVID-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-19 who received invasive mechanical ventilation
and by one fifth in patients receiving oxygen. By contrast, no benefit was found in
patients without respiratory support. 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 effectiveness in the treatment of severe COVID-19 by attenuating the
cytokine storm in a small uncontrolled trial. Bevacizumab is an anti-vascular
endothelial growth factor (VEGF) medication that could potentially reduce
pulmonary edema in patients with severe COVID-19. Eculizumab is a specific
monoclonal antibody that inhibits the proinflammatory complement protein C5.
Preliminary results showed that it induced a drop of inflammatory markers and C-
reactive protein levels, suggesting its potential to be an option for the treatment of
severe COVID-19. It is too early to obtain the exact Ro 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. Several wildlife species were found to harbor potentially evolving
coronavirus strains that can overcome the species barrier. One of the main principles
of Chinese food culture is that live slaughtered animals are considered more
nutritious. 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, and Siamese crocodiles.
DIAGNOSIS OF SARS-CoV-2 (COVID-19):
RNA tests can confirm the diagnosis of SARS CoV-2 (COVID-19) cases with real-
time RT-PCR or next-generation sequencing. At present, nucleic acid detection
techniques, like RT PCR, are considered an effective method for confirming the
diagnosis in clinical cases of COVID 19. Several companies across the world are
currently focusing on developing and marketing SARS-CoV-2-specific nucleic acid
detection kits. Multiple laboratories are also developing their own in-house RT-PCR.
One of them is the SARS-CoV-2 nucleic acid detection kit produced by Shuoshi
Biotechnology (double fluorescence PCR method). Up to 30 March 2020, the U.S.
Food and Drug Administration (FDA) had granted 22 in vitro diagnostics
Emergency Use Authorizations (EUAS), including for the RT-PCR diagnostic panel
for the universal detection of SARS-like beta coronaviruses and specific detection
of SARS-CoV-2, developed by the U.S. CDC. Other emerging viral diseases.
Several therapeutic and preventive strategies, including vaccines,
immunotherapeutic, and antiviral drugs, have been exploited against the previous
CoV outbreaks (SARS-CoV and MERS-CoV). 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. 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. 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
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. 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-19 due
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. 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 Guerin (BCG)
vaccination is a promising strategy for controlling the COVID-19 pandemic and
requires further investigations. All the patients were either asymptomatic (9%) or
had mild disease. No severe or critical cases were seen. The most common symptoms
were fever (50%) and cough (38%). All patients recovered with symptomatic
therapy and there were no deaths. One case of severe pneumonia and multiorgan
dysfunction in a child has also been reported. Similarly the neonatal cases that have
been reported have been mild.
Diagnosis:
A suspect case is defined as one with fever, sore throat and cough who has history
of travel to China or other areas of persistent local transmission or contact with
patients with similar travel history or those with confirmed specimens, like Broncho
alveolar lavage fluid, sputum, nasal swabs, fibro bronchoscope brush biopsy
specimens, pharyngeal swabs, feces, and blood. 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. 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.
Appropriate precautions need to be followed strictly while handling the stools of
patients infected with SARS-CoV-2. Bio-waste materials and sewage from hospitals
must be adequately disinfected, treated, and disposed of properly. The significance
of frequent and good hand hygiene and 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.
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. 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 observed through both in vivo and in
vitro experiments. There is an enhanced nasal secretion observed along with local
edema because of the damage of the host cell, which further stimulates the synthesis
of inflammatory mediators. In addition, these reactions can induce sneezing,
difficulty breathing by causing airway inhibition and elevate mucosal temperature.
These viruses, when released, chiefly affect the lower respiratory tract, with the signs
and symptoms existing clinically. Also, the virus further affects the intestinal
lymphocytes, renal cells, liver cells and T-lymphocytes. Furthermore, the virus
induces T-cell apoptosis, causing the reaction of the T-cell to be erratic, resulting in
the immune system's complete collapse.
Mode of transmission:
In fact it was accepted that the original transmission originated from a seafood
market, which had a tradition of selling live animals, where the majority of the
patients had either worked or visited, although up to now the understanding of the
COVID-19 transmission risk remains incomplete. In addition, while the newer
patients had no exposure to the market and still got the virus from the humans present
there, there is an increase in the outbreak of 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 vision particle, giving
a definite shape to the viral envelope. It binds to the nucleocapsid and acts as a
central organizer of coronavirus assembly. Coronavirus M proteins are highly
diverse in amino acid contents but maintain overall structural similarity within
different genera. The M protein has three transmembrane domains, flanked by a
short amino terminus outside the vision and a long carboxyl terminus inside the
vision. 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.
E Protein:
The coronavirus E protein is the most enigmatic and smallest of the major structural
proteins. It plays a multifunctional role in the pathogenesis, assembly, and release of
the virus. It is a small integral membrane polypeptide that acts as a viroporin (ion
channel). 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
neighbors. 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. 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 anti gens 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. 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 Trans
mission 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. 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 years old) with co-morbidities are more
likely to develop severe respiratory disease that requires hospitalization. The broad-
spectrum activity exhibited by remdesivir will help control the spread of disease in
the event of a new coronavirus outbreak. Chloroquine is an antimalarial drug known
to possess antiviral activity due to its ability to block virus-cell fusion by raising the
endosomal pH necessary for fusion. It also interferes with virus receptor binding by
interfering with the terminal glycosylation of SARS-CoV cellular receptors, such as
ACE2. In a recent multicenter clinical trial that was conducted in China, chloroquine
phosphate was found to exhibit both efficacy and safety in the therapeutic
management of SARS-CoV-2-associated pneumonia. This drug is already included
in the treatment guidelines issued by the National Health Commission of the People's
Republic of China. The preliminary clinical trials using hydroxychloroquine,
another amino quinolone drug, gave promising results. The COVID-19 patients
received 600 mg of hydroxychloroquine daily along with azithromycin as a single-
arm protocol. This protocol was found to be associated with a noteworthy reduction
in viral load. Finally, it resulted in a complete cure; however, the study comprised a
small population and, hence, the United States, tilorone di hydrochloride (ulorone),
was previously found to possess potent antiviral activity against MERS, Marburg,
Ebola, and Chikungunya viruses. 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. 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
regimens compared to lopinavir/ritonavir-IFN-y treatment in MERS-CoV infection.
Remdesivir also inhibits a diverse range of coronaviruses, including circulating
human CoV, zoonotic bat CoV, and pre pandemic zoonotic CoV. Remdesivir is also
considered the only therapeutic drug that significantly reduces pulmonary pathology.
All these findings indicate that remdesivir has to be further evaluated for its animal
species is necessary to prevent the possibility of virus spread and initiation of an
outbreak due to zoonotic spillover. Personal protective equipment (PPE), like face
masks, will help to prevent the spread of respiratory infections like COVID-19. Face
masks not only protect from infectious aerosols but also prevent the transmission of
disease to other susceptible individuals while traveling through public transport
systems. Another critical practice that can reduce the transmission of respiratory
diseases is the maintenance of hand hygiene. However, the efficacy of this practice
in reducing the transmission of respiratory viruses like SARS-CoV-2 is much
dependent upon the size of droplets produced. Hand hygiene will reduce disease
transmission only if the virus is transmitted through the formation of large droplets.
Hence, it is better not to overemphasize that hand hygiene will prevent the
transmission of SARS-CoV-2, since it may produce a false sense of safety among
the general public that further contributes to the spread of COVID-19. Even though
airborne spread has not been reported in SARS-CoV-2 infection, transmission can
occur through droplets and fomites, especially when there is close, unprotected
contact between infected and susceptible individuals.
CONCLUDING REMARKS:
Several years after the global SARS epidemic, the current SARS-CoV-2/COVID-19
pandemic has served as a reminder of how novel pathogens can rapidly emerge and
spread through the human population and eventually cause severe public health
crises. Further research should be conducted to establish animal models for SARS-
CoV-2 to investigate replication, transmission dynamics, and pathogenesis in
humans. This may help develop and evaluate potential therapeutic strategies against
zoonotic CoV epidemics. Present trends suggest the occurrence of future outbreaks
of CoVs due to changes in the climate, and ecological conditions may be associated
with human-animal contact. Live animal markets, such as the Huanan South China
Seafood Market, represent ideal conditions for interspecies contact of wildlife with
domestic birds, pigs, and mammals, which substantially increases the probability of
interspecies transmission of COV infections and could result in high risks to humans
due to adaptive genetic recombination in these viruses. The COVID-19-associated
symptoms are fever, cough, expectoration, headache, and myalgia or fatigue.
Individuals with asymptomatic and atypical with COVID-19 showed typical features
on initial CT, including bilateral multipolar ground-glass opacities with a peripheral
or posterior distribution. 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 retro
sportive studies. However, the extent and duration of immune responses are still
unclear, 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. Compared with convalescent plasma, which has limited
availability and cannot be amplified, monoclonal antibodies can be developed in
larger quantities to meet clinical requirements. Hence, they provide the possibility
for the treatment and pre venation of COVID-19. The neutralizing epitopes of these
monoclonal antibodies also offer important information for vaccine design.
However, the high cost and limited capacity of manufacturing, as well as the problem
of bioavailability, may restrict the wide application of monoclonal antibody therapy.
Vaccines:
Vaccination is the most effective method for a long-term strategy for prevention and
control of COVID-19 in the future. Many different vaccine platforms against SARS-
CoV-2 are in development, the strategies of which include recombinant vectors,
DNA, mRNA in lipid Nano particles, inactivated viruses, live attenuated viruses and
protein subunits. As of 2 October 2020, -174 vaccine candidates for COVID-19 had
been reported and 51 were in human clinical trials (COVID-19 vaccine and
therapeutics tracker). Many of these vaccine candidates are in phase II testing, and
some have already advanced to phase III trials. A randomized double-blinded phase
II trial of an adenovirus type vectored vaccine expressing the SARS-CoV-2 S
protein, developed by Casino Biologicals and the Academy of Military Medical
Sciences of China, was conducted in 603 adult volunteers in Wuhan. The vaccine
has proved to be safe and induced considerable humoral and cellular immune
response in most recipients after a single immunization. The CRISPR-Cas9 gene-
editing tool has been used for inserting genomic alterations in mice, making them
susceptible to MERS-CoV infection. 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, and
advanced ex vivo three-dimensional tracheobronchial tissue, have been explored to
study human CoVs (MERS-CoV). Vero and Huh-7 cells (human liver cancer cells)
have been used for isolating SARS-CoV-2. 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 reposed monkeys. Therefore,
the handling of bats for trading purposes poses a considerable risk of transmitting
zoonotic Cov epidemics. 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. 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. Such markets can be considered a critical place for the origin of
novel zoonotic diseases and have enormous public health significance in the event
of an outbreak. Bats are the reservoirs for several viruses; hence, the role of bats in
the present outbreak cannot be ruled out. In a qualitative study conducted for
evaluating the zoonotic risk factors among rural communities of southern China, the
frequent human-animal interactions along with the low levels of environmental
biosecurity were identified as significant risks for the emergence of zoonotic disease
in local communities. Currently, our knowledge on the animal origin of SARS-CoV-
2 remains incomplete to a large part. The reservoir hosts of the virus have not been
clearly proven. It is unknown whether SARS-CoV-2 was transmitted to humans
through an intermediate host and which animals may act as its intermediate host.
Detection of RaTG13, RmYN02 and pangolin coronaviruses implies that diverse
coronaviruses similar to SARS-CoV-2 are circulating in wildlife. In addition, as
previous studies showed recombination as the potential origin of some sarbeco
viruses such as SARS-CoV, it cannot be excluded that viral RNA recombination
among different related coronaviruses was involved in the evolution of SARS-CoV-
2. Extensive surveillance of SARS-CoV-2 related viruses in China, Southeast Asia
and other regions targeting bats, wild and captured pangolins and other wildlife
species will help us to better understand the zoonotic origin of SARS-CoV-2.
Besides wildlife, researchers investigated the susceptibility of domesticated and
laboratory animals to SARS-CoV-2 infection. The study demonstrated
experimentally that SARS-CoV-2 replicates efficiently in cats and in the upper
respiratory tract of ferrets, whereas dogs, pigs, chickens and ducks were not
susceptible to SARS-CoV-2. The susceptibility of minks was documented by a
report from the Netherlands on an outbreak of SARS-CoV-2 infection in farmed
minks. Although the symptoms in most infected minks were mild, some developed
severe respiratory distress and died of interstitial pneumonia". Other laboratory
investigations are usually nonspecific. The white cell count is usually normal or low.
There may be lymphopenia; a lymphocyte count <1000 has been associated with
severe disease. The platelet count is usually normal or mildly low. The CRP and
ESR are generally elevated but procalcitonin levels are usually normal. A high
procalcitonin level may indicate a bacterial co-infection. The ALT/AST,
prothrombin time, creatinine, D-dimer, CPK and LDH may be elevated and high
levels are associated with severe disease. The chest X-ray (CXR) usually shows
bilateral infiltrates but may be normal in early disease. The CT is more sensitive and
specific.
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 14 d. The symptoms are usually
fever, cough, sore throat, breathlessness, fatigue, malaise among others.