REVIEW ARTICLE

CORONAVIRUS DISEASE 2019 (COVID-19): PUBLIC HEALTH EMERGENCY

Babita Sarangia*, Jyotirmaya Sahooa, Utpal Janab and Guru P. Mohantac

(Received 16 May 2022) (Accepted 06 March 2023)

ABSTRACT

An outbreak of a respiratory sickness started in Wuhan, China in December 2019 and the causative
agent was found be a novel betacoronovirus of the same subgenus as SARSCoV and named se-
vere acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronavirus disease 2019 (COVID-19)
quickly spread around the world, with clinical signs ranging from mild respiratory symptoms to severe
pneumonia and a fatality rate estimated around 2%. Lower respiratory tract infections can occur in im-
munocompromised subjects and the elderly persons. Respiratory droplets are the causative agent for
the person-to-person spread of the disease resembling the spread of influenza. Individual to individual
spread turned into the primary mode of transmission. The transmission of the disease might be more
likely in the earlier stage of infection as the viral RNA levels appear to be higher. Accurate diagnosis in
the early stages of the epidemic helps control the spread of the disease.

Keywords: Betacoronovirus, Coronavirus disease
2019 (COVID-19), Severe Acute Respiratory Syndrome
Coronavirus 2 (SARS-CoV-2), Mode of Transmission,
Preventive Measures
INTRODUCTION
As per the World Health Organization (WHO), viral
diseases proceed to develop and represent a serious
issue to general wellbeing. The severe acute respiratory
syndrome coronavirus (SARS-CoV) and H1N1 influenza
have been considered viral epidemics over the most
recent twenty years. In 2012, the Middle East respiratory
syndrome coronavirus (MERS-CoV) was first detected
in Saudi Arabia1. In December 2019, an outbreak of
respiratory sickness started in Wuhan, China, and a novel
beta coronavirus was identified as the causative agent.
In January 2020, it was named severe acute respiratory
syndrome coronavirus 2 (SARS-CoV-2). Coronavirus
disease 2019 (COVID-19) has quickly spread worldwide
with clinical signs of mild respiratory symptoms to
severe pneumonia. The fatality rate was estimated at
around 2% and increased gradually with the age. The
death percentage in old age people above 80 years is
around 14.8 % and it is 0.2 % in ages between 10 to 39.
Individual to individual transmission is happening both in
the community and healthcare settings. The WHO has
recently declared the COVID-19 epidemic a public health
emergency of universal concern2.
At present, cases of COVID-19 have been found in
numerous nations around the globe. As per the report, up to
the 1st of April 2020, the number of affirmed cases in China
reached 81,590 of which 3,319 were dead, and 76,238
were cured. The number of confirmed cases in the world
reached 879,675 of which 43,944 were dead, and 183,665
were cured3. On the 31st of January, 2020, the WHO
announced that COVID-19 was recorded as the Public
Health Emergency of International Concern (PHEIC),
implying that it might pose risks to different nations and
requires a coordinated international response4. Later,
20,000 cases were confirmed and almost 1000 deaths
have been reported in the European Region by the morning
of 12 March 2020. This made WHO’s Director-General,
Dr. Tedros Adhanom Ghebreyesus announce COVID-19,
as a pandemic5. Globally, as of 1st July 2022, there have
been 545,226,550 confirmed cases including 6,334,728
deaths reported to WHO6.

a
Department of Pharmacy, ARKA Jain University, Gamaharia, Seraikela Kharsawan - 832 108, Jharkhand, India
b
Department of Pharmaceutics, Shiva Institute of Pharmacy, Chandpur, Bilaspur - 174 004, Himachal Pradesh, India
c
Department of Pharmacy, Annamalai University, Annamalai Nagar, Chidambaram- 608 002, Tamil Nadu, India
*For Correspondence: E-mail: aubabita2014@gmail.com

https://doi.org/10.53879/id.60.05.13515

INDIAN DRUGS 60 (05) MAY 2023 7

 The most up-to-date source for the epidemiology of
this emerging pandemic can be obtained from official
sources such as the WHO Novel Coronavirus (COVID-19)
Situation Board and the Johns Hopkins Center for Systems
Science and Engineering site for Coronavirus Global
Cases COVID-19 as depicted in Table I which uses
openly public sources to track the spread of the epidemic.
COVID-19 is a serious disease of international concern6,7.
ORIGIN AND CLASSIFICATION
CoVs are derived from the Latin word Coronam, which
means crown. It is a positive-stranded RNA virus. Virus
appears like a crown under the electron microscope and
the spike glycoprotein on the envelope is responsible for
the crown shape of the virus. CoV belongs to the subfamily
Orthocoronavirinae of the family Coronaviridae and order
Nidovirales. Alpha, beta, delta, and gamma CoVs are
the four genera of the subfamily. Beta CoVs are again
divided into five sub-genera or lineages (Fig.1)8,9. Alpha
and beta CoVs are the two predictable gene sources for
rodents and bats. Whereas delta and gamma CoVs are the
probable gene sources for avian species. Seven human
CoVs (HCoVs) have been identified so far. Some HCoVs
were detected in the mid-1960s and the rest in the new
millennium. 2% of the population are healthy carriers of
a CoV. Acute respiratory infections occur in 5% to 10% of
the population9. HCoVs such as HCoV-229E, HCV-NL63,
and beta CoVs of the A lineage like HCoV-OC43, and
HCoV-HKU1 are the source of common cold and self-
limiting upper respiratory infections in immune-competent
individuals. However, Immunocompromised and elderly
persons suffer from lower respiratory tract infections.
Other beta HCoVs of the B and C lineage such as SARS-
CoV, SARS-CoV-2, and MERS-CoV spread epidemics
which include various respiratory and extra-respiratory
infections. The mortality rates are 10% and 35% in cases
of SARS-CoV and MERS-CoV, respectively. The survivors
with SARS-CoV-2 having clinically significant COVID-19
disease were not observed with long-term complications.
The mortality rate was between 1% to 2% worldwide1.
COVID-19 shows clinical symptoms such as fever,
nonproductive cough, fatigue, dyspnea, myalgia, normal
or diminished leukocyte counts, and radiographic evidence
of pneumonia10,11. Adult males are more preferentially
infected with SARS-CoV-2 than children12,13. By some
estimates, it has a higher reproductive number than
SARS14, and more people have been reported to have
been infected or died from it than SARS15.
Genomics and gene sequencing
CoV is an unsegmented, single-stranded, positive
sense RNA genome of around 30 kb. It is 29,891 bp
8 INDIAN DRUGS 60 (05) MAY 2023
long, with a G+C content of 38%, and enclosed by a 5′-
cap and 3′-poly(A) tail16,17. An envelope containing viral
nucleocapsid covers the virus. The positive sense RNA
is attributed to the helical symmetry in the arrangement
of the nucleocapsid16. The electron micrographs of
SARS-CoV-2 revealed a diverging spherical outline
with some degree of pleomorphism. The diameters of
virion are varying from 60 to 140 nm. The solar structure
of CoV is due to the presence of distinct spikes of 9
to 12 nm18. The CoV genome is arranged linearly as
5′- leader-UTR-replicate-structural genes (S-E-M-N)-3′
UTR-poly(A)19. It also contains accessory genes, such
as 3a/b, 4a/b, and the hemagglutinin-esterase gene
(HE)16. SARS-CoV-2 is similar in genomics but lacks
HE which is the characteristic of some beta CoVs17. The
positive-sense genome of CoVs serves as the mRNA.
The polyprotein gene 1a/1ab (pp1a/1ab) formation may
occur by translation through mRNA20. The nonstructural
proteins (nsps), encoded by the polyprotein gene form
a replication-transcription complex (RTC) in double-
membrane vesicles (DMVs)21. Subsequently, a nested
set of subgenomic RNAs (sgRNAs) is synthesized from
RTC by a discontinuous transcription process22. There
are four important structural proteins such as spike (S),
membrane (M), envelope (E), and nucleocapsid (N)
which are encoded by CoVs (Fig. 2). The S protein is
large and functional. The arrangement of the trimer on
the virion surface gives a crown-like appearance. It is
also considered a class I viral transmembrane protein.
Interaction of this protein with the host cell receptor enables
the infectious virion particles to enter the cell. The M protein
is the most abundant viral protein. It gives a definite shape
to the viral envelope. The E protein is the most enigmatic
and smallest. The N protein is multipurpose. It plays a
role in complex formation with the viral genome. It also
enhances the transcription efficiency by facilitating the M
protein interaction during virion assembly. SARS-CoV-2
genome also contains 15 nsps, nsp1 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 replication9,12,15,23-26.
Mutation in coronavirus
Coronavirus (Fig. 2) just like other viruses holds a
simple structure and has long RNA polymerase tightly
packed into the core surrounded by a protective protein
layer known as capsid or nucleocapsid. There is protein
structure projecting out of envelope are known as spikes
or peplomers. The spikes help the virus adhere to the host
cells and get into the host. While multiplying or replication
there can be slight changes during the replication or
reading codons due to alterations or missing codons,
 Table I: Name of the official sources for COVID-19

Sr. No. Name of official source Weblink References

1 WHO Novel Coronavirus (COVID-19) Situation https://covid19.who.int 6

Board

2 The Johns Hopkins Center for Systems Science https://coronavirus.jhu.edu › map 7

and Engineering site for Coronavirus Global Cases
COVID-19

Table II: Vaccines offered in India

Sr. No. Brand name Mfg. by Vaccine type Age range Efficacy (Highest) References
1 Covishield Astrazeneca Non-Replicating 18+ 91% 109
(Oxford) viral vector
2 Covaxin Bharat Biotech Inactivated 14< 77.8% (In adults 110
>60) 93% overall
3 Moderna NIAID RNA 18+ 90% 111
4 Sputnik V Gamaleya Non-Replicating 12< 91.6% 112
Research Institute Viral vector
5 Johnson & Janssen Non-Replicating 18+ 82% 113
Johnson Pharmaceuticals Viral vector
6 Novavax Novavax Protein Subunit 18+ 90.4% 114
7 ZyCov D Cadila Healthcare DNA based 12-18 yrs 90% or higher 115
Ltd. vaccine

and deletion of amino sugars leading to the formation COVID variants

of an altered protein structure. There can be misreading
of amino groups during the transcription or translation
process. As the virus replication and multiplication is a
repetitive process, the chances of variation or mutation
also increase. This mistake leads to changed information,
making slightly changed viruses with variations known
as variants. Mutation does not change the mechanism
much but may alter transmissibility adherence to a host
that may or may not be more lethal than the previous
one. Even though the mutation may appear in the entire
genome of the virus’s RNA when the subset is observed
a small potion can be easily noticed in the spike proteins.
The spike proteins act as an antigen for the preparation
of vaccination and thus play a crucial role in the study of
viruses and vaccine preparations. Virus keeps multiplying
themselves inside the human host but they are not
competent enough to carry out the multiplication so they
use the host cells. They depend on host cell metabolism,
proteins introduce their RNA or viral DNA to replicate
and form proteins into a cell. Any change in the protein
structure will need different vaccine preparations, studies,
and measures27, 28.
The variant is slightly different from the same entity.
In the case of the SARS-CoV 2 virus, it is a mutation
in viruses that they adapt to survive in the changing
environment; every time a virus is transferred from one
person to another, there is a change in the strains. Few
variants are as follows29:
1. α Variants (Alpha variants) from the UK, aka B.1.1.7.
2. β Variants (Beta variants) from South Africa aka
B.1.351. Found in parts of Nigeria. It is more easily
transmissible but less than the original variants
3. γ Variants (Gamma variants) from Brazil aka P.1.
These are first detected in Brazilian people traveling
to Japan in Jan 2021. These are observed to be more
contagious than their preceding variants.
4. Δ Variants: From India aka B.1.617.2. It is about
50% more contagious/ transmissible and more lethal
variants than the actual virus.
5. Ω(Omicron): From South Africa aka B.1.1.529 was
reported to WHO on November 2021 to be less lethal
than its previous variants.

INDIAN DRUGS 60 (05) MAY 2023 9

 MHV-A

Γ-CoVs
IBV
α-CoVs SW1
HCoV-229E
HCoV-NL63
TGEV δ-CoVs

Β-CoVs HKU11
Bat-SL ZC45
Bat-SL ZX 21 KKU17
2019-nCoV
Family: Coronaviridea SARS-CoV
Order: Nidovirales Subfamily :Orthocoronavirina MERS-CoV
HCoV-OC43
: The phylogenetic tree of Coronavirus (representative CoVs, with the new HKU-1
MHV-A59
avirus 2019‐nCoV highlighted in red)8,9
Γ-CoVs
IBV
SW1

δ-CoVs

HKU11
KKU17

Fig. 1: The phylogenetic tree of Coronavirus (representative CoVs, with the new coronavirus 2019-nCoV)8,9
Fig: 1. The phylogenetic tree of Corona virus (representative CoVs, with the new coronavirus
2019‐nCoV highlighted in red)8,9

Fig. 2: Structure of Coronavirus9,12,15,23-26

Fig. 2: Structure of Coronavirus9,12,15,23-26
10 INDIAN DRUGS 60 (05) MAY 2023
 High

Medium

Low

Fig. 3: Predicted infection from COVID-19 in INDIA. Total infections (Asymptomatic+

Hospital+ Symptomatic)106

Fig. 3: Predicted infection from COVID-19 in INDIA. Total infections (asymptomatic+ hospital+ symptomatic)106

Fig. 3: Predicted infection from COVID-19 in INDIA. Total infections (Asymptoma

Hospital+ Symptomatic)106

High

Medium

Low

Fig. 4: Predicted hospitalizations from COVID-19 in INDIA (hospitalized cases)106

Fig. 4: Predicted Hospitalizations from COVID-19 in INDIA (Hospitalized cases)106

INDIAN DRUGS 60 (05) MAY 2023 11

CLINICAL MANIFESTATIONS
Much like the manifestations of SARS-CoV and
MERS-CoV infections, patients with positive COVID-19
show clinical symptoms such as fever, nonproductive
cough, fatigue, dyspnea, myalgia, normal or diminished
leukocyte counts, and radiographic evidence of
pneumonia12,14,30,31. Less common symptoms include
headache, dizziness, abdominal pain, diarrhea, nausea,
and vomiting12,30. Pregnant and non-pregnant women have
similar characteristics32. Common laboratory abnormalities
found in COVID-19 patients are lymphopenia 25,26,33
prolonged prothrombin time, and elevated lactate
dehydrogenase30. ICU-admitted patients had more
laboratory abnormalities12,30. Some patients had elevated
aspartate aminotransferase, creatine kinase, creatinine,
and C-reactive protein12,33,34. Most patients showed normal
serum procalcitonin levels12, 30,33.
PATHOGENESIS
Even though the pathogenesis of COVID-19 is
ineffectively comprehended, the similar mechanisms of
SARS-CoV and MERS-CoV still can give us a great deal of
data on the pathogenesis of SARS-CoV-2 contamination
to encourage our recognition of COVID-1935, although
the analysis of the risk associated with the transmission
rate is incomplete. Epidemiologic investigation in Wuhan
towards the start of the outbreak recognized an underlying
relationship with a seafood market that sold live animals.
Subsequently, the market was closed for disinfection since
most patients had worked or visited36. The progression of
COVID-19 was due to the primary mode of transmission
which is attributed to individual-to-individual spread. It is
estimated that the respiratory droplets are the causative
agent for the person-to-person spread of SARS-CoV-2
resembling the spread of influenza. The virus gets
discharged in the respiratory secretions because of droplet
transmission. A person can be infected when he or she
comes into direct contact with the mucous membrane of
the infected person while talking, sneezing, and coughing.
When a person touches his or her eyes, nose, or mouth
after touching the infected surface can cause infection.
Droplets generally do not linger in the air and travel not
exceeding two meters (about six feet)37. The size of the
droplets also determines the severity of the respiratory
infection. Respiratory droplets are > 5-10 µm in diameter
whereas droplet nuclei are ≤ 5 µm in diameter38. As per
the literature the mode of primary transmission was
through respiratory droplets and contact routes39,40,41,42,12,34.
Droplet transmission refers to the presence of microbes
within droplet nuclei. Droplets travel over distances
greater than 1m and remain for a longer period in
12 INDIAN DRUGS 60 (05) MAY 2023
the air. Hence airborne transmission is different from
droplet transmission. As the mechanism of transmission
is uncertain, airborne precautions are recommended
routinely in some countries. Infected droplets can spread
1–2 m and deposit on surfaces. In favorable atmospheric
conditions, the virus can remain viable on surfaces for days.
However, common disinfectants like sodium hypochlorite,
hydrogen per‐ oxide, etc. can destroy the virus in less
than a minute43. The virus is also present in the stool.
Water contamination with subsequent transmission of
the infection through aerosolization/feco oral route is also
assumed44. Transplacental transmission from pregnant
women to their fetus is not clear till now but the post-
natal transmission is described45. The incubation period
varies from 2 to 14 d [median 5 d]. The virus enters the
respiratory mucosa via angiotensin receptor 2 (ACE)46. It
mainly affects the respiratory system of our body such as
the nasopharyngeal tract and lungs because the ACE2
receptor is highly present in those areas to which spikes
of SARS-CoV-2 bound. The life cycle of the virus with the
host consists of 5 steps; attachments(A), penetration(P),
biosynthesis(B), mutation(M), and release(R). Once
viruses bind to host receptor(A), they enter into host cells
through endocytosis or membrane fusion(P). Viral content
is released inside the host cells and the viral RNA enters
the nucleus for replication. The viral mRNA converts
itself into viral proteins through translation. The new viral
proteins are made and get mutated(M) inside the host
cell, replicate, and released(R) outside for the new host47.
TRANSMISSION
The transmission of the disease is faster at the initial
stage due to higher viral RNA levels soon after the onset
of symptoms in comparison to the later stage of infection48.
Additional data are yet to produce for confirmation of this
hypothesis. The transmission rate might be influenced by
infection control interventions and locations in the case of
an individual with symptomatic infection. The secondary
transmission rate is documented to be from 1 to 5 percent
among tens of thousands of close contacts of confirmed
patients in China as indicated by a joint WHO-China
report49. The symptomatic secondary attack rate was
found to be 0.45 percent in the U.S.50. Transmission of
SARS-CoV-2 has also been reported from asymptomatic
individuals or individuals within the incubation period but
the degree to which it occurs stays obscure51,52,53,54,33. A
few serological tests are under development. Serologic
screening may provide information on the epidemiologic
analysis and asymptomatic infection55. RNA sample has
been detected in blood and stool specimens in the case
of SARS-CoV-2 infection56,57. In some cases, the live virus
has been cultured from stool58. At room temperature, the
virus is stable in faeces and urine for at least 1-2 days. In
stool of diarrhea patients who have higher pH than normal
stool, the virus is stable for up to 4 days. Further infection
can be prevented by the use of disinfectants and fixatives.
The minimal reduction in virus concentration is observed
after 21 days at 4°C and -80 °C. For quick reduction in
virus concentration, it should be heated at 56 °C at around
10000 units per 15 mins. SARS-CoV-2 is more stable
than HCoVs as one log reduction in virus concentration
was observed at stable room temperature59. The spread
of infection was not due to fecal or oral transmission as
reported jointly by WHO-China49.
DIAGNOSIS
COVID-19 is diagnosed by auxiliary examinations
such as nucleic acid detection, immune identification
technology Point-of-care Testing (POCT) of IgM/IgG,
enzyme-linked immunosorbent assay (ELISA), CT scan,
and blood culture. Clinical manifestations of the infection
are based on epidemiological history. However, the
patients are showing atypical clinical symptoms such
as respiratory symptoms, cough, fever, dyspnea, viral
pneumonia, etc. Hence, auxiliary examinations are
necessary along with the epidemiological history for
diagnosis4. The availability of testing will vary based on
which country a person lives in and the increasing number
of cases on daily basis also affects the availability of the
testing. A normal or decreased total white blood cell count
can be observed in the early stage. Total lymphocyte
count also decreases at the initial stage.
The ARDS (Acute Respiratory Stress Syndrome) 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
failure60. It is reported that the liver enzymes, LDH, muscle
enzymes, and C-reactive protein level are increased,
whereas lymphopenia appears to be a negative prognostic
factor. Patients in critical condition show increased D-dimer
value but the procalcitonin level is normal. Decreased
blood lymphocytes count and multiorgan imbalance such
as high amylase and coagulation disorders were also found
in critical conditions. Some epidemiologic and clinical
information is required to determine who should have
testing performed. Certain criteria are fixed in the U.S. to
put the persons under investigation (PUI). Patients with
positive COVID-19 have developed symptoms of acute
respiratory illness such as cough, and difficulty breathing
with fever as reported by the U.S. CDC. PUI are put in place
of infection control and prevention measures immediately
after a recommendation and tested for other sources
of respiratory infection. In addition to the exaggerated
INDIAN DRUGS 60 (05) MAY 2023 13
inflammatory response, hepatic tissue injury is also seen in
patients with COVID-19 due to compensatory proliferation
of hepatocytes and upregulation of ACE2 expression61.
Epidemiologic factors were used for the confirmation of
COVID-19. Within 14 days of symptom onset, the person
who was in close contact with a laboratory-confirmed
COVID-19 patient or has a history of travel from affected
geographic areas like China, Italy, Iran, Japan, South
Korea, etc. are included under epidemiologic factors1.
The WHO recommends collecting specimens from
both the lower respiratory tract such as expectorated
sputum, endotracheal aspirate, or bronchoalveolar
lavage (BAL) and the upper respiratory tract (nasal- and
oropharyngeal samples). Mechanically ventilated patients
were subjected to the collection of BAL samples as
lower respiratory tract samples seem to remain positive
for a longer period. Collected samples were stored at a
temperature of 4ᵒ C. Reverse polymerase chain reaction
(RT-PCR) technology is used for the amplification of the
genetic materials extracted from the collected samples.
Subsequently, a double-stranded DNA molecule from
an RNA mold is developed through this process. The
genetic code particularly for CoV is conserved after
sufficient development of genetic material. The probes
used are based on the initial gene sequence released
by the Shanghai Public Health Clinical Center & School
of Public Health, Fudan University, Shanghai, China
on Virological.org. It was subsequently followed by
confirmatory evaluation by additional labs. In case of a
positive result, the test is repeated for verification. Viral
clearance is required before release from observation.
It is evaluated by repeating the laboratory tests in case
of positive COVID-19 diagnosed patients1. .
Clinically proven specific antiviral agents are not
available for SARS-CoV-2 infection62,63. The important
supportive treatment like the use of broad-spectrum
antibiotics to cover secondary bacterial infection, oxygen
therapy, and conservation fluid management is coming
under the COVID-19 management strategy64, whereas
hemodynamic support is essential for managing septic
shock. Several potential therapeutic agents have been
recommended to reuse the existing antiviral agents
or develop effective interventions against this novel
coronavirus based on the research on molecular
mechanisms of coronavirus infection65 and the genomic
organization of SARS-CoV-266.
TREATMENT
A novel nucleotide analog, remdesivir show strong
activity against SARS-CoV-2 under in vitro condition.
Randomized trials are under process to evaluate the
efficacy of remdesivir which is a potential target for
moderate or severe COVID-1967. Remdesivir also shows
strong activity in both in vitro and in vivo conditions
against related coronaviruses including SARS and MERS-
CoV68,69. Remdesivir is used compassionately in the case
of one of the first patients with COVID-19 in the U. S.
which is described through an investigational new drug
application case report70. Any clinical effect of remdesivir
against COVID-19 remains unknown. Both chloroquine
and hydroxychloroquine inhibit SARS-CoV-2 in vitro,
although hydroxychloroquine is reported to be a more
potent antiviral agent71. Several clinical trials are under
process in China to evaluate the efficacy of chloroquine
and hydroxychloroquine against COVID-1972. Chloroquine
shows strong antiviral impacts on SARS-CoV infection
of primate cells. The inhibitory effects on the cells are
examined before or after exposure of the drug to a virus
that was therapeutically advantageous. It also indicates
the prophylactic use of infected persons. Chloroquine
interferes with terminal glycosylation of the ACE2 receptor.
Additionally, it elevates endosomal pH73. The combined
protease inhibitors lopinavir and ritonavir have primarily
been used for HIV infection. The combination also shows
the in vitro activity against the SARS-CoV and in vivo
activity against MERS-CoV respectively74,75. Many case
studies depicting the use of this combination against
COVID-19 are available76,77,78 but its efficacy is unclear.
Enormous randomized trials are being conducted for the
evaluation. Another IL-6 inhibitor, tocilizumab, is used
in severe conditions as reported in the guidelines from
China’s National Health Commission. Still, the drug is
under clinical trial for evaluation79.
Several attempts are being made to design and
develop vaccines for CoV infection, mostly by targeting
the spike glycoprotein. We are dependent solely on
implementing effective infection control measures to
lessen the risk of possible nosocomial transmission due
to the lack of effective antiviral therapy and vaccines80.
The majority of the treatment options and strategies
that are being evaluated for COVID-19 have been
taken from previous experiences in treating SARS-CoV,
MERS-CoV, and other emerging viral diseases. Several
therapeutic and preventive strategies, including vaccines,
immunotherapeutics, and antiviral drugs, have been
exploited against the previous SARS-CoV and MERS-
CoV outbreaks81-86. The S protein plays a significant role
in the induction of protective immunity against SARS-
CoV87. The development of an effective vaccine depends
upon the identification of the immunodominant region.
The C-terminal domain of the S1 subunit is identified as
14 INDIAN DRUGS 60 (05) MAY 2023
the immunodominant region88. Hence, knowledge and
understanding of S protein will help to develop the potential
vaccine candidates based on the whole S protein, S protein
subunits, or specific potential epitopes of S protein against
SARS-CoV-2. 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 Ii-Key peptide COVID-19 vaccine
are under preclinical trials89. Similarly, the WHO, on its
official website, has mentioned a detailed list of COVID-19
vaccine agents that are under consideration. Vaccines
that are under different phases of trials are live attenuated
virus vaccines, formaldehyde alum inactivated vaccine,
adenovirus type 5 vector vaccine, LNP-encapsulated
mRNA vaccine, DNA plasmid vaccine, and S protein,
S-trimer, and Ii-Key peptide as a subunit protein vaccine,
etc90. Effective vaccines and viral shedding are essential
to reduce the severity of the disease which will help to
control coronavirus outbreaks. In addition to recombinant
DNA, and protein vaccines other vaccination strategies
such as live-attenuated virus, viral vectors, inactivated
virus, and subunit vaccines are tested against SARS-CoV
291. The very first experimental coronavirus vaccine was
injected into volunteers in the US on 16th March 2020. The
initial trial included 45 people aged 18 to 55 and doses of
mRNA-1273 into the arms of healthy participants at Kaiser
Permanente Washington Research Institute (KPWHRI).
It was considered the first-stage study of a potential
COVID-19 immunization. The study included the tech
company operations manager Jennifer Haller. He was
the first participant in this study. The biotech company
Moderna prepared an investigational vaccine that is free
of any part of the actual coronavirus and cannot cause
infection. It rather incorporates a short segment of lab-
grown messenger RNA and the various doses are being
tested to check the safety, immune response, and any
side effects after collecting the blood samples. According
to Anthony Fauci of the U.S. National Institute of Health,
a vaccine will not be available for widespread use for
another 12 to 18 months even if all goes well92.
The effectiveness of a vaccine can be evaluated
by giving deliberately it to the people who are infected
with the bug in question. Vaccines for the flu, common
cold, and other respiratory illness have been developed
through these challenging studies. The signs of illness
after infection were observed by tracking the record of the
participants. A study conducted by hVIVO – a subsidiary
of pharmaceutical-services company Open Orphan PLC
in London, has attracted more than 20,000 volunteers in
exchange for a fee of £3,500 ($4,480) which provided
detailed insights into the course of COVID-19 infection
with potentially positive health implications. Such
investigation played important role in the development
of the vaccines for the treatment of coronavirus infection.
These trials don’t replace the larger field studies, but
they help give direction on whether a vaccine is worth
pursuing93. Ø Individuals that are immunocompromised should
CONTROL AND PREVENTION
The basic reproductive number (R0) is an indication of
an increase or decrease in the endemic. The R0 value has
been estimated with varying results and interpretations.
An average number of infections resulting from one
infected individual in a fully susceptible population can
be measured by the R0 value94. Studies from previous
outbreaks were found to be 2.7 for SARS and 2.4 for
2009 pandemic H1N1 influenza95,96. The epidemic will
increase if R0 is greater than 1 whereas R0 is 2.2 for
COVID-1997. Further analysis of 12 available studies
found that R0 was 3.2898. R0 is also considered a super
spreader as it is an average value. It may hugely be
responsible for outbreaks within large clusters but not
influence the R0 value99. During the acute phase or pre-
pandemic, R0 may be unstable94. Hence it is required to
focus on reducing the value to less than 1 to control the
infection. Preventive measures are the only strategy to
limit the spread of cases. Preventive measures included
the isolation of the patients with careful infection control.
Simultaneously appropriate measures have to be taken
during the diagnosis and clinical care of the infected
patient. Sputum induction and droplet contact should be
avoided during sample collection. Airborne precautions
should be taken while collecting the sample. The effective
way to stop the spread of the disease is by disrupting the
chain of transmission. Further spreading of the infection
in clinics and hospitals can be limited by applying triage,
following correct infection control measures, isolating the
cases, and contact tracing100. 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
recovery101. The WHO and other organizations have
issued the following general recommendations:
Ø Avoid close contact with subjects suffering from acute
respiratory infections.
INDIAN DRUGS 60 (05) MAY 2023 15
Ø Wash your hands frequently, especially after contact
with infected people or their environment.
Ø Avoid unprotected contact with farm or wild animals.
Ø People with symptoms of acute airway infection should
keep their distance, cover coughs or sneezes with
disposable tissues or clothes and wash their hands.
Ø Application of strict hygiene measures for the
prevention and control of infections particularly in
emergency medicine departments
avoid public gatherings.
PRACTICE POINTS FROM AN INDIAN
PERSPECTIVE
A total of 1,397 COVID-19 cases including 49
Foreign Nationals had been reported from 27 states/
union territories across India as on 31 March 2020 at
08.30 PM according to the Ministry of Health & Family
Welfare102. All states had issued appropriate instructions
for all children below 10 years of age and all citizens
above 65 years (except for public representatives/
government servants/medical professionals) to remain
at home and avoid mass gatherings unless there is a
medical reason and essential services requirement. A
high-level Group of Ministers is constantly reviewing
the status of cases in India. Necessary steps are
being implemented by the Government of India across
states. Social distancing measures have been issued
by the government advisory board to slow down the
rate and extent of disease transmission. Non-urgent
hospitalization and elective surgeries are avoided by the
instruction of the health advisory board in consultation
with professional associations. This was to maintain
a strategic distance from hospital-related infections
to the vulnerable and prepare hospitals effectively for
meeting current and future challenges presented by
COVID-19103. Ministry of Health and Family Welfare was
regularly evaluating quarantine facilities. In addition to
that preparedness of the hospital in terms of adequate
isolation wards, OPD blocks, availability of testing kits,
medicines, and personal protective equipment (PPEs),
etc. are evaluated. All public hospitals have been directed
to ensure sufficient accessibility of protective gear for all
healthcare workers104. A confirmed covid-19 case must
be hospitalized and placed in a single patient room with
negative pressure – a minimum of 6 charges per hour.
Exhausted air has to be filtered through High-Efficiency
Particulate Air (HEPA) and medical personnel entering
the room need to wear PPE particularly facemask, gown,
and eye protection105. The greatest risk of COVID-19
is transmission to healthcare workers. In the SARS
outbreak of 2002, 21% of those affected were healthcare
workers106.
COVID-19 modeling with India SIM predicted that the
community transmission of COVID-19 in INDIA most likely
started in early March 2020. To stop the transmission,
state or local containment was the best option rather
than National containment. Approximately 300 and 400
million Indians were likely to be infected by July 2020,
without interventions. Most of these cases would be mild.
Somewhere between April and May 2020, around 100
million individuals would be infected. Amongst them,
approximately 10 million would be severed and about
2-4 million will require hospitalization (Fig. 3 & Fig. 4). As
per the report, this may be the most dangerous period.
This peak load would be reduced by 75% by generalized
social distancing. It would be a major issue of hospital
outbreaks of COVID-19 induced by the admission of
infected patients into hospitals. Thus there is a need for
large temporary hospitals to handle this patient load over
the next three months period. Hospital-based secondary
transmission may fuel the epidemic107.
On 11th July 2020, India started Phase-I clinical trials,
16 candidates were opted and examined at AIIMS, Delhi.
Usually, it takes 8-10 years for vaccines to reach the
market from labs, but in the case of COVID vaccines due
to emergencies, this period is shortened to a few months.
The shortening of the time duration was done by limiting
the time of regulatory approvals (licensing registration
applications and submissions authorized by CDSCO) and
not the specific approvals and thus not comprising with
vaccines safety and efficacy108. Due to crises phases of
clinical trials were done by combining various steps of
different phases. Out of 25 vaccine trials, India offered
a total of 7 vaccines109-115 (Table II). DCGI permitted 2
vaccines- Bharat Biotech’s Covaxin and ZyCoV-D by
Zydus Cadila116,117.
CONCLUSION
Since the first outbreak of coronavirus (COVID-19) in
Wuhan, China, the disease spread worldwide. The current
COVID-19 pandemic is an international public health
problem. This new virus outbreak has challenged the
economic, medical, and public health infrastructure of the
whole world. Individuals at extreme ages are at higher risk.
Risk is more significant in the case of immunocompromised
patients. Complete elimination of risk is not possible
but prudent adjustments may be warranted. All health
care workers should understand the presentation of the
disease and workup. Supportive care by the health care
16 INDIAN DRUGS 60 (05) MAY 2023
workers also plays an important aspect in the response.
Health professionals should be aware of the precautions
necessary to avoid the transmission and spread of the
disease. Accurate diagnosis in the early stages of the
epidemic helps control the spread of the disease. More
so future outbreaks of viruses are likely to continue. So,
comprehensive measures should be devised to prevent
future outbreaks. However, the development of suitable
therapeutic agents such as designing antiviral drugs
and vaccines against COVID-19 will help to control the
infection.
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