INTRODUCTION:
A group of viruses named,
Coronaviruses (CoVs) are able to co-infect humans and other vertebrate animals.
Respiratory system, liver, gastrointestinal system, and central nervous system of
humans, birds, livestock, mice, bats, and many other wild animals are effected by
Coronavirus infections. For example, severe acute respiratory syndrome (SARS) in
2002 and the Middle East respiratory syndrome (MERS) in 2012 were both coronaviruses
that has been transmitted from animals to humans.
The World Health Organization (WHO), China on 31st December 2019,
informed of cases of pneumonia of unknown etiology detected in Wuhan City.
The causative organism for this infectious disease is a new strain of Coronavirus.
This new strain of coronavirus was officially
named as SARS-CoV-2 on 11th February, 2020 and the disease caused by this virus was called coronavirus
disease 2019 (COVID-19).
Asian J. Pharm. Tech. 2022;
12(1):63-69.
National Health Commission of the People’s
Republic of China stated that SARS-CoV-2 was transmitted from wild bats to humans,
and this CoVs can transmit from person to person. SARS-CoV-2 and SARS-CoV have similar
behavior pattern and gene sequence. Older people, effected by SARS-CoV-2
with chronic respiratory disease, diabetes, cardiovascular disease, and cancer
are more likely to develop serious illness. Near about 200 countries are affected
by this disease and in more than 160 countries it is spreading through local transmission.
WHO on 11th March, 2020 has declared the situation as a pandemic. Slow
down of this transmission can be achieved by knowing the cause of the disease and
how it spreads. COVID-19 spreads through saliva droplets and discharge from the
nose of the infected person when they coughs or sneezes. At present, there are no
specific treatments or vaccines available for COVID-19. However, many clinical trials
are going on to evaluate potential treatment against this virus1,2,3.
Coronavirus (CoV) are a large family of single-stranded RNA viruses that can
be isolated in different animal species. These are the virus that cause diseases
in mammals and birds. This viruses can cross species barriers and can cause, in humans, illness
ranging from the common cold to more severe diseases such as Middle East respiratory
syndrome (MERS) and Severe acute respiratory syndrome coronavirus (SARS). The potential
of SARS-CoV-2
to grow to become a
pandemic worldwide seems to be a serious public health risk.
Epidemiology:
The coronavirus
cause various symptoms such as breathing difficulty, pneumonia, fever, and lung
infection. It is a common animal virus, but in few cases it affects human also.
Coronaviruses belong
to a class of viruses, that causing illness in human and others that circulate among
animals, including camels, cats, bats, etc. Rarely, animal corona viruses may evolve
and jump species to infect people and then spread between people as witnessed during
the outbreak of Severe Acute Respiratory Syndrome (SARS, 2003) and Middle East Respiratory
Syndrome (MERS, 2014). The etiologic agent responsible for current outbreak of SARS-CoV-2
is a novel coronavirus closely related to SARS-Coronavirus. Table 1 provides a comparison of the epidemiological characteristics
of SARS-CoV, MERS-CoV, and SARS-CoV-2.
In humans, the transmission of SARS-CoV-2 can
occur via respiratory secretions (directly through droplets from coughing or sneezing,
or indirectly through contaminated objects or surfaces as well as close contacts).
Nosocomial transmission has been described as an important driver in the epidemiology
of SARS and MERS and has also been documented in COVID-19. Current estimates of
the incubation period of COVID range from 2-14 days. Most common symptoms include
fever, fatigue, dry cough and breathing difficulty. Upper respiratory tract symptoms
like sore throat, rhinorrhoea, and gastrointestinal symptoms like diarrhoea and
nausea/ vomiting are seen in about 20% of cases. The deaths reported are mainly
among elderly population particularly those with co-morbidities. The published studies
from China indicated that most cases with SARS-CoV-2-infected pneumonia were aged
above 50 yr (median age: 55-59 yr), predominantly men (54-68%) and had chronic medical
conditions (46.4-51%). The common symptoms included fever, fatigue, dry cough, myalgia,
dyspnoea, expectoration and diarrhoea1,3,4,5
Etiology:
Severe Acute Respiratory
Syndrome Coronavirus-2 (SARS-CoV-2) causes COVID-19 and it is a novel, enveloped
single-stranded RNA virus. It is having spike glycoproteins on its envelope. This spike
glycoprotein is responsible for its crown like structure and it can be viewed under
an electron microscope. Corona virus comes under Coronaviridae family and
Orthocoronavirinae subfamily. It is classified into four different classes
namely a. Alphacoronavirus (alphaCoV), b. Betacoronavirus (betaCoV), c. Deltacoronavirus
(deltaCoV), and d. Gammacoronavirus (gammaCoV). Furthermore, the betaCoV genus divides
into five sub-genera or lineages. Genomic characterization has shown that probably
bats and rodents are the gene sources of alphaCoVs and betaCoVs. On the contrary,
avian species seem to represent the gene sources of deltaCoVs and gammaCoVs.
Members of this large family of
viruses can cause respiratory, enteric, hepatic, and neurological diseases in different
animal species, including camels, cattle, cats, and bats. To date, seven human CoVs
(HCoVs) — capable of infecting humans — have been identified.
Table 1: Comparison of epidemiological
characteristics between SARS-CoV, SARS-CoV-2, and MERS-CoV.
|
Features
|
SARS-CoV-2
|
SARS-CoV
|
MERS-CoV
|
|
Estimated *R0 value
|
2.68
|
2-5
|
>1
|
|
Host of virus
|
Natural Host: Bats
Intermediate Host: Pangolins
Terminal Host: Humans
|
Natural Host: Chinese horseshoe bats
Intermediate Host: Masked palm civets
Terminal Host: Humans
|
Natural Host: Bats Intermediate Host: Dromedary camels
are intermediate hosts, Terminal Host: Humans
|
|
Transmission mode
|
Human-to-human. It
can spread through physical contact, fomites, aerosol droplets, zoonotic transmission,
nosocomial transmission,
|
Human-to-human. It
can spread through nosocomial transmission, aerosol droplets, opportunistic airborne
transmission, zoonotic transmission, fecal-oral transmission,
|
Limited human-to-human
transmission, zoonotic transmission, Respiratory transmission, nosocomial transmission,
aerosol transmission
|
|
Incubation period
|
6.4 days (range: 0-24
days)
|
4.6 days
|
5.2 days
|
*R0 = reproduction
number.
CoVs are responsible for 5-10% of
acute respiratory infections. It has been estimated that 2% of the population are
deemed healthy carriers of these viruses. Some common human CoVs include HCoV-OC43,
HCoV-HKU1, HCoV-229E, and HCoV-NL63. In the immunocompetent, these CoVs clinically
present with self-limiting respiratory infections and common colds. In the elderly
and immunocompromised, they can involve the lower respiratory tracts. Other human
CoVs such as MERS-CoV, SARS-CoV, and SARS-CoV-2 present with pulmonary and extra-pulmonary
features. SARS-CoV-2, which is responsible for the COVID-19 pandemic, is a type
of beta-COV. Genomic characterization studies of the new strain have indicated an
89% nucleotide match with bat SARS-like CoVZXC21. The virus is sensitive to ultraviolet
light and heat. SARS-CoV-2 bind to their target cells through angiotensin-converting
enzyme 2 (ACE2), which is expressed in the lungs. Furthermore, these viruses can
be functionally inactivated with the use of ethanol (60%), ether (75%), and chlorine-containing
disinfectants.
Structure of COVID-19 (SARS-CoV-2):
The structure of COVID-19 consists of
the following:
a.
Spike protein
(S),
b.
Hemagglutinin-esterease
dimer (HE),
c.
Membrane glycoprotein
(M),
d.
Envelope protein
(E)
e.
Nucleoclapid
protein (N) and RNA
Spike protein (S) is heavily glycosylated, utilizes
an N-terminal signal sequence to gain access to the ER and mediate attachment to
host receptors. It is the largest structure and makes the distinct spikes on the
surface of the virus.
RNA is the genome of the virus.
Nucleocapsid protein (N) binds to RNA in vitro
and is heavily phosphorylated. N proteins binds the viral genome in a beads on a
string type conformation. This protein likely helps tether the viral genome to replicase-transcriptase
complex (RTC), and subsequently package the encapsulated genome into viral particles.
Envelope protein (E) is found in small quantities in
within the virus. It is most likely a transmembrane protein and with ion channel
activity. The protein facilitates assembly and release of the virus and has other
functions such as ion channel activity. It is not necessary for viral replication
but it is for pathogenesis.
Membrane protein (M) is the most abundant structural
protein. It does not contain signal sequence and exists as a dimer in the virion.
It may have two different conformations to enable it to promote membrane curvature
as well as bind to nucleocapsid.
Hemagglutinin-esterase dimer protein
(HE) is present
in a subset of betacoronaviruses. The protein binds sialic acids on surface glycoproteins.
The protein activities are thought to enhance S protein-mediated cell entry and
virus spread through the mucosa. Figure 1 shows the structure of COVID 19.
Figure 1: Structure of COVID 19
Transmission:
The first cases of the CoVID-19
disease were linked to direct exposure to the Seafood Wholesale Market of Wuhan
and it is believed that the virus is transmitted from the animal-to-human. This
virus can also transmit from human-to-human, and symptomatic people are the most
frequent source of COVID-19 spread. The possibility of transmission before symptoms
develop seems to be infrequent, although it cannot be excluded. Moreover, there
are suggestions that individuals who remain asymptomatic could transmit the virus.
This data suggests that the use of isolation is the best way to contain this epidemic.
As with other respiratory pathogens,
including flu and rhinovirus, the transmission is believed to occur through respiratory
droplets from coughing and sneezing. Aerosol transmission is also possible in case
of protracted exposure to elevated aerosol concentrations in closed spaces. Analysis
of data related to the spread of SARS-CoV-2 in China seems to indicate that close
contact between individuals is necessary. The spread, in fact, is primarily limited
to family members, healthcare professionals, and other close contacts.
Based on data from the first cases
in Wuhan and investigations conducted by the China CDC and local CDCs, the incubation
time could be generally within 3 to 7 days and up to 2 weeks as the longest time
from infection to symptoms was 12.5 days (95% CI, 9.2 to 18). This data also
showed that this novel epidemic doubled about every seven days, whereas the basic
reproduction number (R0 - R naught) is 2.2. In other words, on average, each patient
transmits the infection to an additional 2.2 individuals. Of note, estimations of
the R0 of the SARS-CoV epidemic in 2002-2003 were approximately 3.
It must be emphasized that this
information is the result of the first reports. Thus, further studies are needed
to understand the mechanisms of transmission, the incubation times and the clinical
course, and the duration of infectivity.
Pharmaceutical interventions:
As of now there is no approved specific drug
or vaccine for cure or prevention of COVID-19.
However as per Indian Council of Medical Research
(ICMR), Hydroxychloroquine has been recommended as chemoprophylaxis drug for use
by asymptomatic healthcare workers managing COVID-19 cases and asymptomatic contacts
of confirmed COVID-19 cases. In addition a combination of Hydroxychloroquine and
Azithromycin has been advocated for use in severe cases of COVID-19 under medical
supervision.
No antiviral treatment for SARS-CoV-2 infection
has been proven to be effective. A few historical control studies or case reports
indicate the effectiveness of combination of lopinavir/ritonavir against SARS-CoV
and MERS-CoV infections. Ritonavir-boosted lopinavir was approved for use amongst
HIV-infected individuals in September 2000 by the U.S. Food and Drugs Administration.
The drug has been used for over 15 years in India. Lopinavir is always used with
ritonavir to reduce the dose of lopinavir and increase the plasma levels of lopinavir
as ritonavir inhibits CYP3A isoenzyme. Lopinavir and ritonavir are antiretroviral
protease inhibitors used in combination as a second-line drug for the treatment
of HIV-1 infection in children and adults and have limited side effects. In a historical
control study, lopinavir/ritonavir with ribavirin amongst SARS-CoV patients was
associated with substantial clinical benefit. Findings from in vitro and
clinical studies, together with the availability and safety profiles of lopinavir/ritonavir
and interferon beta-1b (IFN-β1b) suggest that the combination of these agents
has potential efficacy for the treatment of patients with MERS-CoV. Oral treatment
with lopinavir/ritonavir in the marmoset model of MERS-CoV infection resulted in
modest improvements in MERS disease signs, including decreased pulmonary infiltrates
identified by chest X-ray, decreased interstitial pneumonia and decreased weight
loss In view of the earlier evidence about the effectiveness of lopinavir/ritonavir
against SARS and MERS-CoV, the ICMR has suggested off-label emergency use of lopinavir/ritonavir
combination for symptomatic COVID-19 patients detected in the country. Use of IFN-β1b
and ribavirin was not considered due to their reported toxicity, whereas oseltamivir
was not considered due to its unproven efficacy against CoVs.
Several agents are being used under clinical
trial and compassionate use protocols based on in vitro activity (against SARS-CoV-2
or related viruses) and on limited clinical experience. Efficacy has not been established
for any drug therapy.
Antimicrobials with potential activity against
SARS-CoV-2:
Chloroquine – In vitro and limited clinical
data suggest potential benefit. Hydroxychloroquine – In vitro and limited clinical
data suggest potential benefit.
Lopinavir; Ritonavir - Role in the treatment
of COVID-19 is unclear. Preclinical data suggested potential benefit; however, more
recent data has failed to confirm.
Remdesivir – Investigational and available only
through expanded access and study protocols; several large clinical trials are underway.
o Favipiravir – Investigational use is being studied. Table 2 listed out the various
antimicrobial agents active against SARS-CoV-25,6,7.
Chloroquine Hydroxychloroquine
Lopinavir Ritonavir
Remdesivir Favipiravir
2-Deoxy-d-glucose
Figure 2: Molecular structure of different drugs
used against COVID 19
Non-Pharmaceutical interventions:
Nonpharmaceutical
Interventions are actions, apart from getting vaccinated and taking medicine, that
people and communities can take to help slow the spread of illnesses like influenza
(flu) or COVID-19. In the absence
of proven drug or vaccine, non-pharmaceutical interventions is the main stay
for containment of COVID-19 cluster.
Preventive public health measures:
Different preventive public health measures
are listed below and shown in figure number 3.
Figure 3: Different non pharmaceutical interventions
to prevent COVID 19
Quarantine and isolation:
Quarantine and Isolation are important mainstay
of cluster containment. These measures help by breaking the chain of transmission
in the community.
Quarantine:
Quarantine refers to separation of individuals
who are not yet ill but have been exposed to COVID-19 and therefore have a potential
to become ill.
Isolation:
Isolation refers to separation of individuals
who are ill and suspected or confirmed of COVID-19. Ideally, patients can be isolated
in individual isolation rooms or negative pressure rooms with 12 or more air-changes
per hour.
Social distancing measures:
For the cluster containment, social distancing
measures are key interventions to rapidly curtail the community transmission of
COVID-19 by limiting interaction between infected persons and susceptible hosts.
The following measures can be taken:
a. Closure of schools, colleges and work places
b. Cancellation of mass gatherings
c. Advisory to avoid public places
d. Cancellation of public transport
Figure 4: Different social distancing measures
to prevent COVID 19
Prevention:
Preventive measures are the current
strategy to limit the spread of cases. Because an epidemic will increase as long
as R0 is greater than 1 (COVID-19 is 2.2), control measures must focus on reducing
the value to less than 1.
Preventive strategies are focused
on the isolation of patients and careful infection control, including appropriate
measures to be adopted during the diagnosis and the provision of clinical care to
an infected patient. For instance, droplet, contact, and airborne precautions should
be adopted during specimen collection, and sputum induction should be avoided.
The WHO and other organizations
have issued the following general recommendations:
·
Avoid close
contact with subjects suffering from acute respiratory infections.
·
Wash your hands
frequently, especially after contact with infected people or their environment.
·
Avoid unprotected
contact with farm or wild animals.
·
People with
symptoms of acute airway infection should keep their distance, cover coughs or sneezes
with disposable tissues or clothes and wash their hands.
·
Strengthen,
in particular, in emergency medicine departments, the application of strict hygiene
measures for the prevention and control of infections.
·
Individuals
that are immunocompromised should avoid public gatherings.
The most important strategy for
the populous to undertake is to frequently wash their hands and use portable hand
sanitizer and avoid contact with their face and mouth after interacting with a possibly
contaminated environment.
Healthcare workers caring for infected
individuals should utilize contact and airborne precautions to include PPE such
as N95 or FFP3 masks, eye protection, gowns, and gloves to prevent transmission
of the pathogen.
Meanwhile, scientific research is
growing to develop a coronavirus vaccine. In recent days, China has announced the
first animal tests, and researchers from the University of Queensland in Australia
have also announced that, after completing the three-week in vitro study, they are
moving on to animal testing. Furthermore, in the U.S., the National Institute for
Allergy and Infectious Diseases (NIAID) has announced that a phase 1 trial has begun
for a novel coronavirus immunization in Washington state8-14.
Deterrence and Patient Education:
Patients and families should receive
instruction to:
Avoid close contact with subjects
suffering from acute respiratory infections.
Wash their hands frequently, especially
after contact with sick people or their environment.
Avoid unprotected contact with farm
or wild animals.
People with symptoms of acute airway
infection should keep their distance, cover coughs or sneezes with disposable tissues
or clothes and wash their hands.
Immunocompromised patients should
avoid public exposure and public gatherings. If an immunocompromised individual
must be in a closed space with multiple individuals present, such as a meeting in
a small room; masks, gloves, and personal hygiene with antiseptic soap should be
undertaken by those in close contact with the individual. In addition, prior room
cleaning with antiseptic agents should be undertaken and performed before exposure.
However, considering the danger involved to these individuals, exposure should be
avoided unless a meeting, group event, etc. is a true emergency.
Strict personal hygiene measures
are necessary for the prevention and control of this infection.
CONCLUSIONS:
The COVID-19 pandemic is spreading
throughout the globe at an alarming rate. It is causing more deaths and infections
than SARS or MERS. Elderly patients are at the highest risk of fatality. The rapid
spread of disease warrants intense surveillance and isolation protocols to prevent
further transmission. There is no confirmed medication or vaccine available for
the disease COVID-19. The global impact of this new epidemic is yet uncertain.
REFERENCES:
1. K. Nalini Devi, Juliana Shanthi Rosy.
ECMO therapy for COVID-19. Asian J. Nursing Education and Research. 2021; 11(2):299-301.
Peiris JS, Lai ST, Poon LL, Guan Y, Yam LY, Lim W, et al. Lancet, 2003;361:1319–25.
2. Subhashis Debnath, Runa Chakravorty,
Donita Devi. COVID 19 and its management. Asian Journal of Pharmaceutical Research.
2021; 11(2):117-1.
3. Archana B. Chavhan, Pavan S. Jadhav,
Satish Shelke. COVID 19: Outbreak, Structure and Current therapeutic strategies.
Asian J. Pharm. Tech. 2021; 11(1):76-83.
4. Gurvishal Sinha. The vista of Pandemic
in the world and its adaptation by Society: Statistical significant precautions
on COVID. Asian Journal of Management. 2020;11(4):453-456.
5. Ritik S. Jain, Tejas G. Jain, Suraj
K. Ishikar. Impact of Covid-19 on Changing Habits and Health Issues of the Public.
Asian Journal of Management. 2020;11(4):524-528.
6. Niloy Sarkar, Bijoy Kumar Mandal,
Soumya Paul. Activity, Effect on Human and Salvation from effect of COVID-19. Asian
Journal of Management. 2021; 12(2):228-4.
7. B. V. Naresh. A Review of the 2019
Novel Coronavirus (COVID-19) Pandemic. Asian J. Pharm. Res. 2020; 10(3):233-238.
8. Vaishnavi. K. Patil, Azam. Z. Shaikh.
Corona (Covid - 19). Asian J. Pharm. Res. 2020; 10(4):275-285.
9. Vishwanath Biradar, Prerana Dalvi.
Impact of COVID19 on Child Health: Parents Perspective. Int. J. Nur. Edu. and Research.
2020; 8(4):463-467.
10. Atul Sharma, Keerthi Mohanan. Obstacles
Faced by Nurses working in Covid-19 Unit: A Developing Country view Point. Asian
J. Nursing Education and Research. 2020; 10(4):459-462.
11. Darshana Kumari Wankhede. COVID-19-
Problem faced by Indians during Lockdown. Asian J. Nursing Education and Research.
2020; 10(4):501-504.
12. Melisa Fernandes, Jyoti R. Thakur,
Manisha S. Gavanje. A Study to assess knowledge regarding covid-19 among Nursing
students. Asian J. Nursing Education and Research. 2021; 11(1):65-67.
13. Subhashis Debnath, Runa Chakravorty,
Donita Devi. A Review on Role of Medicinal plants in Immune system. Asian J. Pharm.
Tech. 2020; 10(4):273-277.
14. Mayur S. Jain, Shashikant D. Barhate.
Corona viruses are a family of viruses that range from the common cold to MERS corona
virus: A Review. Asian J. Res. Pharm. Sci. 2020; 10(3):204-210.
