The document discusses the outbreak of SARS-CoV-2, highlighting its transmission from humans to companion animals and the potential implications for human-to-human transmission dynamics. It details the clinical pathology of COVID-19, including symptoms, treatment protocols, and the importance of radiological assessments in diagnosis. Additionally, it emphasizes the need for effective prevention strategies and the ongoing evolution of the virus, which could impact its transmissibility and pathogenicity.
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The document discusses the outbreak of SARS-CoV-2, highlighting its transmission from humans to companion animals and the potential implications for human-to-human transmission dynamics. It details the clinical pathology of COVID-19, including symptoms, treatment protocols, and the importance of radiological assessments in diagnosis. Additionally, it emphasizes the need for effective prevention strategies and the ongoing evolution of the virus, which could impact its transmissibility and pathogenicity.
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significant outbreak occurs due to a_ virus-like
SARS-CoV-2.
There is a steady increase in the reports of
COVID-19 in companion and wild animals around
the world, Further studies are required to evaluate
the potential of animals (especially companion
animals) to serve as an efficient reservoir host that
can further alter the dynamics of human-to-human
transmission (330). To date, two pet dogs (Hong
Kong) and four pet cats (one each from Belgium and
Hong Kong, two from the United States) have tested
positive for SARS-CoV-2 (335). The World
Organization for Animal Health (OTE) has confirmed
the diagnosis of COVID-19 in both dogs and cats
due to human-to-animal transmission (331). The
similarity observed in the gene sequence of SARS-
CoV-2 from an infected pet owner and his dog
further confirms the occurrence of human-to-animal
transmission (333). Even though asymptomatic,
feline species should be considered a potential
transmission route from animals to humans (326).
However, currently, there are no reports of SARS-
CoV-2 transmission from felines to human beings.
Based on the current evidence, we can conclude that
cats are susceptible to SARS-CoV-2 and can get
infected by human beings. However, evidence of cat-out on the isolated virus confirmed that there is a
potential risk for the reemergence of SARS-CoV
infection from the viruses that are currently
circulating in the bat population (105).
CLINICAL PATHOLOGY OF SARS-CoV-2
(COVID-19)
The disease caused by SARS-CoV-2 is also
named severe specific contagious pneumonia
(SSCP), Wuhan pneumonia, and, recently, COVID-
19 (110). Compared to SARS-CoV, SARS-CoV-2
has less severe pathogenesis but has superior
transmission capability, as evidenced by the rapidly
increasing number of COVID-19 cases (111). The
incubation period of SARS-CoV-2 in familial
clusters was found to be 3 to 6 days (112). The mean
incubation period of COVID-19 was found to be 6.4
days, ranging from 2.1 to 11.1 days (113). Among an
early affected group of 425 patients, 59 years was the
median age, of which more males were affected
(114). Similar to SARS and MERS, the severity of
this nCoV is high in age groups above 50 years (2,
115). Symptoms of COVID-19 include fever, cough,
myalgia or fatigue, and, less commonly, headache,
hemoptysis, and diarrhea (116, 282). Compared to
the SARS-CoV-2-infected patients in Wuhan duringrespiratory infection (SARI) and respiratory
distress, shock or hypoxaemia. Patients with
SARI can be given conservative fluid therapy
only when there is no evidence of shock.
Empiric antimicrobial therapy must be started
to manage SARI. For patients with sepsis,
antimicrobials must be administered within 1
hour of initial assessments. The WHO and CDC
recommend that glucocorticoids not be used in
patients with COVID-19 pneumonia except
where there are other indications (exacerbation
of chronic obstructive pulmonary disease).°?
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
multiorgan system failure.*°progress from the initial focal unilateral to diffuse
bilateral ground-glass opacities and will further
progress to or coexist with lung consolidation
changes within | to 3 weeks (159). The role played
by radiologists in the current scenario is very
important. Radiologists can help in the early
diagnosis of lung abnormalities associated with
COVID-19 pneumonia. They can also help in the
evaluation of disease severity, identifying its
progression to acute respiratory distress syndrome
and the presence of secondary bacterial infections
(160). Even though chest CT is considered an
essential diagnostic tool for COVID-19, the
extensive use of CT for screening purposes in the
suspected individuals might be associated with a
disproportionate risk-benefit ratio due to increased
radiation exposure as well as increased risk of cross-
infection. Hence, the use of CT for early diagnosis of
SARS-CoV-2 infection in high-risk groups should be
done with great caution (292).
More recently, other advanced diagnostics have
been designed and developed for the detection of
SARS-CoV-2 (345, 347, 350-352). A reverse
transcriptional loop-mediated isothermal
amplification (RT-LAMP), namely, iLACO, has been
developed for rapid and colorimetric detection of this07:25 MOvws 7 Au
was linked to a family member and 26
children had history of
travel/residence to Hubei province in
China. 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 [19]. Similarly the neonatal
cases that have been reported have
been mild [20].
Diagnosis [21]
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 histarv or thase with confirmed
< ® aShelp us to control the spread of this virus. However,
this is both challenging as well as time-consuming
due to the present extent of infection (226). The
current scenario demands effective implementation
of vigorous prevention and control strategies owing
to the prospect of COVID-19 for nosocomial
infections (68). Follow-ups of infected patients by
telephone on day 7 and day 14 are advised to avoid
any further unintentional spread or nosocomial
transmission (312). The availability of public data
sets provided by independent analytical teams will
act as robust evidence that would guide us in
designing interventions against the COVID-19
outbreak. Newspaper reports and social media can be
used to analyze and reconstruct the progression of an
outbreak. They can help us to obtain detailed patient-
level data in the early stages of an outbreak (227).
Immediate travel restrictions imposed by several
countries might have contributed significantly to
preventing the spread of SARS-CoV-2 globally (89,
228). Following the outbreak, a temporary ban was
imposed on the wildlife trade, keeping in mind the
possible role played by wild animal species in the
origin of SARS-CoV-2/COVID-19 (147). Making a
permanent and bold decision on the trade of wild
animal species is necessary to prevent the possibilitybetween the genome sequence of the new
coronavirus (SARS-CoV-2) and SARS-like CoVs,
the comparative analysis recognized a furin-like
cleavage site in the SARS-CoV-2 S protein that is
missing from other SARS-like CoVs (99), The furin-
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 furin
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 (100). 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 (101). Possibly related to the viral
pathogenesis is the recent finding of an 832-
nucleotide (nt) deletion in ORF8, which appears to
reduce the replicative fitness of the virus and leads to
attenuated phenotypes of SARS-CoV-2 (256).
Coronavirus is the most prominent example of atreated symptomatically along with oxygen therapy.
In such cases where the patients progress toward
respiratory failure and become refractory to oxygen
therapy, mechanical ventilation is necessitated. The
COVID-19-induced septic shock can be managed by
providing adequate hemodynamic support (299).
Several classes of drugs are currently being
evaluated for their potential therapeutic action
against SARS-CoV-2. Therapeutic agents that have
anti-SARS-CoV-2 activity can be broadly classified
into three categories: drugs that block virus entry
into the host cell, drugs that block viral replication as
well as its survival within the host cell, and drugs
that attenuate the exaggerated host immune response
(300). An inflammatory cytokine storm is commonly
seen in critically ill COVID-19 patients. Hence, they
may benefit from the use of timely anti-inflammation
treatment. Anti-inflammatory therapy using drugs
like glucocorticoids, cytokine inhibitors, JAK
inhibitors, and chloroquine/hydroxychloroquine
should be done only after analyzing the risk/benefit
ratio in COVID-19 patients (301). There have not
been any studies concerning the application of
nonsteroidal anti-inflammatory drugs (NSAID) to
COVID-19-infected patients. However, reasonable
pieces of evidence are available that link NSAIDSplits Tree phylogeny analysis.
In the unrooted phylogenetic tree of different
betacoronaviruses based on the S protein, virus
sequences from different subgenera grouped into
separate clusters. SARS-CoV-2 sequences from
Wuhan and other countries exhibited a close
relationship and appeared in a single cluster (Fig. 1).
The CoVs from the subgenus Sarbecovirus appeared
jointly in SplitsTree and divided into three
subclusters, namely, SARS-CoV-2, bat-SARS-like-
CoV (bat-SL-CoV), and SARS-CoV (Fig. 1). In the
case of other subgenera, like Merbecovirus, all of the
sequences grouped in a single cluster, whereas in
Embecovirus, different species, comprised of canine
respiratory CoVs, bovine CoVs, equine CoVs, and
human CoV strain (OC43), grouped in a common
cluster. Isolates in the subgenera Nobecovorus and.
Hibecovirus were found to be placed separately
away from other reported SARS-CoVs but shared a
bat origin.
CURRENT WORLDWIDE SCENARIO OF
SARS-CoV-2
This novel virus, SARS-CoV-2, comes under the
subgenus Sarbecovirus of the Orthocoronavirinae
subfamily and is entirely different from the virusesstalk (45). Recently, structural analyses of the S
proteins of COVID-19 have revealed 27 amino acid
substitutions within a 1,273-amino-acid stretch (16).
Six substitutions are located in the RBD (amino
acids 357 to 528), while four substitutions are in the
RBM at the CTD of the $1 domain (16). Of note, no
amino acid change is seen in the RBM, which binds
directly to the angiotensin-converting enzyme-2
(ACE2) receptor in SARS-CoV (16, 46). At present,
the main emphasis is knowing how many differences
would be required to change the host tropism.
Sequence comparison revealed 17 nonsynonymous
changes between the early sequence of SARS-CoV-2
and the later isolates of SARS-CoV. The changes
were found scattered over the genome of the virus,
with nine substitutions in ORFlab, ORF8 (4
substitutions), the spike gene (3 substitutions), and
ORF7a (single substitution) (4). Notably, the same
nonsynonymous changes were found in a familial
cluster, indicating that the viral evolution happened
during person-to-person transmission (4, 47), Such
adaptive evolution events are frequent and constitute
a constantly ongoing process once the virus spreads
among, new hosts (47), Even though no functional
changes occur in the virus associated with this
adaptive evolution, close monitoring of the viral