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COVID 19 Pandemic, Mechanism of Pathogenesis, Preventions and Possible Cures to Save Humanity: A Study

Authors:
  • ayurvet reserach foundation
  • AYURVET RESEARCH FOUNDATION

Abstract

The name "coronavirus" is derived from Latin corona, meaning "crown" or "wreath due to the characteristic appearance of virions , which have a fringe of large, bulbous surface projections creating an image reminiscent of a crown or of a solar corona. Human coronaviruses were discovered in the 1960s. The third novel coronavirus to emerge in this century is called SARS-CoV-2. It caused coronavirus disease 2019 (COVID-19), which emerged from China in December 2019 and was declared a global pandemic by the World Health Organization on March 11, 2020. The virus enters into the host body through the mouth, nose and eye. From there, the virus makes its way down into the air sacs inside the lungs, known as alveoli. Once in the alveoli, the envelope spike glycoprotein present in the virus binds to its cellular receptor, angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2. There are two commonly used nucleic acid detection technologies forSARS-CoV-2 are real-time quantitative polymerase chain reaction (RT-qPCR) and high-throughput sequencing. With no sure shot vaccine/ drug in sight till late 2021, medical practioners are using existing therapies and repurposing drugs to save lives. Prevention is the only way to stay safe and healthy. Immunity plays an important role in this disease, so it important have nutritious and healthy food to boost the immunity.
Journal of Infertility and Reproductive Biology, 2020, Volume 8, Issue 2, Pages: 18-21
18
COVID 19 Pandemic, Mechanism of Pathogenesis,
Preventions and Possible Cures to Save Humanity:
A Study
Samanwita Banerjee, Jainendra Gupta, Anil Kanaujia
Ayurvet Research Foundation, Chidana, Haryana, India
Received: 06/05/2020 Accepted: 03/06/2020 Published: 20/06/2020
Abstract
The name "coronavirus" is derived from Latin corona, meaning "crown" or "wreath due to the characteristic appearance
of virions , which have a fringe of large, bulbous surface projections creating an image reminiscent of a crown or of a solar
corona. Human coronaviruses were discovered in the 1960s. The third novel coronavirus to emerge in this century is called SARS-
CoV-2. It caused coronavirus disease 2019 (COVID-19), which emerged from China in December 2019 and was declared a global
pandemic by the World Health Organization on March 11, 2020. The virus enters into the host body through the mouth, nose and eye.
From there, the virus makes its way down into the air sacs inside the lungs, known as alveoli. Once in the alveoli, the envelope spike
glycoprotein present in the virus binds to its cellular receptor, angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2. There are
two commonly used nucleic acid detection technologies forSARS-CoV-2 are real-time quantitative polymerase chain reaction (RT-
qPCR) and high-throughput sequencing. With no sure shot vaccine/ drug in sight till late 2021, medical practioners are using existing
therapies and repurposing drugs to save lives. Prevention is the only way to stay safe and healthy. Immunity plays an important role in
this disease, so it important have nutritious and healthy food to boost the immunity.
Keywords: COVID 19, SARS-CoV-2, Vaccine, ACE2, RT-q PCR
1 Introduction
1
Coronaviruses belongs to the family Coronaviridae,
order Nidovirales, which cause diseases
in mammals and birds (1-3). The family is further divided into
Torovirinae and Coronavirinae sub families. The sub family
Coronavirinae is further sub categorized into alpha-, beta-,
gamma- and delta- COVs (2-5). In humans, coronaviruses
cause respiratory tract infections that can range from mild to
lethal. Among the group there are few lethal varieties which
cause SARS, MERS, and COVID-19. The symptom varies
with different species such as in chickens, they cause an upper
respiratory tract disease, while in cows and pigs they
cause diarrhea. It was first discovered in the 1930s when an
acute respiratory infection of domesticated chickens was
shown to be caused by infectious bronchitis virus (IBV) (3).
Human coronaviruses were discovered in the 1960s (3, 6).
Four of the seven known coronaviruses that sicken people
cause only mild to moderate disease. Three can cause more
serious, even fatal, disease. SARS coronavirus (SARS-CoV)
emerged in November 2002 and caused severe acute
respiratory syndrome (SARS). That virus disappeared by
2004. Middle East respiratory syndrome (MERS) is caused by
the MERS coronavirus (MERS-CoV). Transmitted from an
animal reservoir in camels, MERS was identified in
September 2012 and continues to cause sporadic and localized
outbreaks. The third novel coronavirus to emerge in this
century is called SARS-CoV-2. It caused coronavirus disease
2019 (COVID-19), which emerged from China in December
2019 and was declared a global pandemic by the World
Health Organization on March 11, 2020 (6, 7).
Corresponding author: Samanwita Banerjee, Ayurvet
Research Foundation, Chidana, Haryana, India. E-mail:
samanwita.banerjee@arfmail.in.
2 Morphology
The name "coronavirus" is derived from Latin corona,
meaning "crown" or "wreath due to the characteristic
appearance of virions , which have a fringe of large, bulbous
surface projections creating an image reminiscent of a crown
or of a solar corona. It is spherical and pleomorphic and
having a diameter of 0.12 micrometer. The virus envelops
consist of lipid bi layer with structural protein such as
membrane, spike anchored on it. There are small spike like
surface proteins also known as hemagglutanin esterase (HE).
Inside the envelope, there is the nucleocapsid, which is
formed from multiple copies of the nucleocapsid (N) protein,
which are bound to the positive-sense single-
stranded RNA genome in a continuous beads-on-a-string type
conformation. The combined structure protects the virus
outside the host cell as shown in Fig 1. The genome one of
the largest among RNA viruses which size ranges from 26.4
to 31.7 kilobases and has a 5′ methylated cap and a 3′
polyadenylated tail (3). The two-thirds of the genome
ORF1a/b encodes polyproteins, which form the viral replicase
transcriptase complex and the other ORFs on the one-third of
the genome encode four main structural proteins: spike (S),
envelope (E), nucleocapsid (N) and membrane (M) proteins,
as well as several accessory proteins (8).
19
Figure 1: Structure of corona virus (9)
3 Modes of transmission
Patients with COVID-19 show symptoms such as fever,
nonproductive cough, sneezing, dyspnea, myalgia, fatigue,
normal or decreased leukocyte counts, shortness of breathing
and radiographic evidence of pneumonia which are similar to
the symptoms of SARS-CoV and MERS-CoV infections (8).
People get infected in the neighbourhood of infected person
who has symptoms from the virus includes cough and
sneezing as it spreads through airborne zoonotic droplets
shown in Fig. 2 (4, 6). The severity and onset of COVID-19 is
dependent on age and immunity of the patients. The
incubation period ranges from 2- 14 days and can be last for
more than 2 weeks (2, 10). Many studies showed that Patients
with comorbidity such as hypertension, coronary heart
disease, obesity, are at high risk (10, 11).
Figure 2: Airborne zoonotic droplets transmission (12)
4 Pathogenesis of COVID 19
The pathogenic mechanism of Coronavirus seems to be
complex (10). The life cycle of the corona virus includes four
steps i.e. attachment and entry, Replicase protein expression,
replication and transcription and assembly and release (1).
The virus enters into the host body through the mouth, nose
and eye. From there, the virus makes its way down into the
air sacs inside your lungs, known as alveoli. Once in the
alveoli, the envelope spike glycoprotein present in the virus
binds to its cellular receptor, angiotensin-converting enzyme 2
(ACE2) for SARS-CoV-2. Once the virus’ RNA has entered a
cell, new copies are made and the host cell is killed in the
process, releasing new viruses to infect neighboring cells in
the alveolus and cause inflammation in lung which in turn
activate the immune response. During this process of unfolds,
fluid begins to accumulate in the alveoli which stimulate nasal
secretion, dry cough, sneezing and making breathing difficult.
In severe cases, the immune system’s response to the
inflammation cause cytokine storm i.e. it starts affecting its
own body cells than to virus it’s trying to defeat which lead to
acute respiratory distress syndrome (ARDS). At this stage, the
surfactant that helps keeping the alveoli being collapsing has
been diluted and fluid containing debris is imparing the gas
exchange process that supplies oxygen to our bloodstream. In
severe cases, it enters into the bloodstream, resulting in septic
shock and multiple organ failure (10, 13, 14). To better
survive in host cells, SARS-CoV and MERS-CoV use
multiple strategies to avoid immune responses (8).
5 Diagnosis of COVID 19
Clinical diagnosis of COVID-19 is mainly based on
epidemiological history, clinical manifestations and some
auxiliary examinations, such as nucleic acid detection, CT
scan, immune identification technology (Point-of-care Testing
(POCT) of IgM/IgG, enzyme-linked immunosorbent assay
(ELISA) and blood culture. However, the clinical symptoms
and signs of patients infected withSARS-CoV-2 are highly
atypical, including respiratory symptoms, cough, fever,
dyspnea, and viral pneumonia. Therefore, auxiliary
examinations are necessary for the diagnosis of COVID-19,
just as the epidemiological history. There are two commonly
used nucleic acid detection technologies for SARS-CoV-2 are
real-time quantitative polymerase chain reaction (RT-qPCR)
and high-throughput sequencing (8). The high throughput
sequencing is limited due to its equipment dependency and
highly expensive whereas RT-q PCR is effective and
commonly used for the detection of viruses from the
respiratory secretion of patients. In this RT q PCR techniques
two primers and probes are used in ORF1ab and N gene
region for the detection. RT qPCR has to detect both the
targeted region of viral genome present in the patients to be
confirmed as infected. Although RT qPCR are specific but
false negative rate cannot be denied (8). So, some of the
medical practitioner use Ct scan of the chest is along with the
RT q PCR. In CT Scan of the patients shows clear view of the
abnormalities if presents. The typical CT images show
bilateral pulmonary parenchymal ground-glass and
consolidative pulmonary opacities, sometimes with a rounded
morphology and a peripheral lung distribution (8, 10). Both
the diagnosis method has its own limitation. Currently, POCT
of IgM/IgG and ELISA kits for SARS-CoV-2 have been
developed and pre-tested by some companies and have shown
higher detection rates than nucleic acid detection (8,15).
Another laboratory investigation that are based on the count
of white blood cell count. The lymphocyte counts less than
1000 has been associated with severe disease. There also
decrease level of platelet count (15). It is necessary for the
development of specific and detection kit for the diagnosis of
COVID-19.
6 Prevention and its mechanism
In world, the cases of COVID 19 increases with high rate,
so it is very much essential to opt the prevention. COVID 19
is inversely proportional to the immune system of the
individual. Most of the people get infected with COVID-19
have mild symptoms and recover due to the proper
medication, early stage or good immunity, whereas some
patients are deceased due to the low immunity with having the
previous diseases such as asthma, heart disease, diabetics, etc.
there is no clinically proven drug for the treatment of COVID-
19. Prevention is the only way to stay safe and healthy. As per
the WHO guidelines, there are few prevention guidelines
which need to be followed during this pandemic.
20
1. Washing of Hand Frequently: Washing your hands
with soap and water or using alcohol-based hand rub
regularly and thoroughly kills viruses that may be on
your hands (16, 17).
2. Maintain social distancing: Maintain at least 1 metre (3
feet) distance between yourself and anyone who is
coughing or sneezing. When someone coughs or sneezes,
they spray small liquid droplets from their nose or mouth
which may contain virus. If you are too close, you can
breathe in the droplets, including the COVID-19 virus if
the person coughing has the disease (16, 17). Avoid
touching eyes, nose and mouth: Hands touch many
surfaces and can pick up viruses. Once contaminated,
hands can transfer the virus to your eyes, nose or mouth.
From there, the virus can enter your body and can make
you sick (16, 17).
3. Practice respiratory hygiene: Make sure you, and the
people around you, follow good respiratory hygiene.
This means covering your mouth and nose with your
bent elbow or tissue when you cough or sneeze. Then
dispose of the used tissue immediately. Droplets spread
virus. By following good respiratory hygiene, you
protect the people around you from viruses such as cold,
flu and COVID-19 (16, 17).
4. Seek medical care early: Stay home if you feel unwell.
If you have a fever, cough and difficulty breathing, seek
medical attention and call in advance (16).
5. Cloth face covering: Wear cloth face covering in the
public setting where the social distance cannot be opted.
It is additionally advised to use cloth mask rather than
N95 mask to avoid spreading of the virus and help
people who may have the virus and do not know it from
transmitting it to others (18).
6. Disinfecting surfaces: Proper cleaning of frequently
touched surfaces such as door, cabinet, etc. has to be
performed using household detergent and water because
COVID-19 virus survives on surfaces for many hours
(19).
Apart from the aforementioned steps, there are several
other steps, which can be opt by individual as a prevention
such as resting and avoiding overexertion, drinking sufficient
amount of water, avoiding smoking and smoky areas, etc. (1).
7 Current development strategies on treatment
of COVID 19
Currently, there is no clinically approved drug or vaccines are
available which show effectiveness against COVID-19. Many
trials are on process for drug development in worldwide. The
supportive treatments are under trial to relive discomfort
during illness. In February Hydroxychloroquine was found to
effectively reduce COVID-19 illness. Preliminary results from
a trial indicated that chloroquine is effective and safe in
COVID-19 pneumonia, "improving lung imaging findings,
promoting a virus-negative conversion, and shortening the
disease course but it has numerous, potentially serious, side
effects. High doses of hydroxychloroquine are proving to be
lethal (20). Remdesevir, adenosine nucleotide analog act as a
viral RNA- dependent RNA polymerase inhibitor that inhibits
RNA synthesis in coronavirus and act as an antiviral agent
(21). Recombinant human monoclonal antibody can bind with
receptor binding site and can be effective against COVID 19
infection. Vaccine development with a live-attenuated virus,
viral vectors, inactivated virus, subunit vaccines, recombinant
DNA, and proteins vaccine is another mode of strategy which
can reduce the severity of outbreak (8). Serum Institute if
India, Moderna BioNtech USA and others are in various
stages of vaccine development. It will take at least 18 months
or by late 2021 to establish effectiveness and safety.
8 Using existing therapies and repurposing
drugs to save lives
With no sure shot vaccine/ drug in sight till late 2021,
medical practioners are using existing therapies and
repurposing drugs to save lives.
a. Combination of Hydroxychloroquine and the antibiotic
azithromycin has shown some effectiveness in a very
small French study and reports from China. Chloroquine
act as an effective antiviral drug against SARS-CoV-2
infection at entry and post entry its stage and prevent the
virus cell fusion by interfering with glycosylation of
ACE2 receptor and its binding with spike protein (21,
22).
b. Arbidol which is also known as Umifenovir inhibits viral
fusion in the targeted membrane, that blocks the viral
entry and Oseltamivir suppresses the viral neuraminidase
and inhibits the release of viral particle into the targeted
cells (22, 23).
c. India has so far approved the combination of two
antivirals drugs (Lopinavir and ritonavir) that targets
viral protease to treat COVID -19 (20).
d. Convalescent plasma (Antibody therapy) - Giving sick
patients with antibody rich plasma from those who have
recovered is a century old therapy with proven track
records.
e. Clot bursting drugs - tissue plasminogen activator is used
to treat heart attack and stroke patients, may work to treat
Covid-19. Clinical trials will take few months before
safety is ensured.
f. Ayurvedic medicines and herbal drugs are also used
along with the therapeutic drug for boosting the
immunity. Specific prophylaxis includes Sanjeevani bati,
chitrakadi, combination of Guduchi, (Tinospora
cordifolia) Shunthi (Zingiber officinale) and Haridra
(Curcuma longa Linn.). Sanjeevani bati act against cold
cough and communicable diseases and also strengthens
and rejuvenates the immune system. Other herbs such,
Ocimum sanctum, Glycyrrhiza glabra, Adhatoda vasica,
Andrographis paniculata, Swertiachirata, Moringa
oleifera, Triphala and Trikatu has antiviral properties and
inhibits the viral protease (24).
9 Conclusion
The sudden outbreak of the infectious disease COVID-19
is a threat to each and every individual globally. The
remarkable point of this infection is its spreading rate among
the communities. Scientific communities are working on the
development of drugs and vaccines to eradicate the disease
from the root level. During the period of this pandemic, it is
necessary to opt the precautionary measures and avoid the
spreading among the community. It is also important not to
believe the rumors about the pandemic and depend on the
reliable and authentic information. Immunity plays an
important role in this disease, so it important have nutritious
and healthy food to boost the immunity as per ministry of
AYUSH, Govt. of India.
Aknowledgment
We would like to convey our thanks to Shri Mohan Ji
Saxena, Managing Trustee for his valuable guidance and
support.
21
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... ACE2 expresses abundantly in lung alveolar epithelium and small intestine enterocytes [18], which might be the reason for the hypervulnerability of respiratory and gastrointestinal organs to COVID-19 infection [19][20][21][22]. ACE2 also expresses in the kidney, liver, spleen, and testes and could be responsible for various clinical manifestations of the disease, such as liver diseases [18,[23][24][25]. ...
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Corona virus causes respiratory infection including pneumonia, cold, sneezing and coughing while in animal it causes diarrhea and upper respiratory diseases. Corona virus transmitted human to human or human to animal via airborne droplets. Corona virus enters in human cell through membrane ACE-2 exopeptidase receptor. WHO and ECDC advised to avoid public place and close contact to infected persons and pet animals. Firstly Corona virus (2019-nCoV) was isolated from Wuhan market China at 7 Jan. 2020.
Article
Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/L (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/L could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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