COVID 19 - A brief details about COVID-19 , HISTORY, STRUCTURE, MODE OF TRANSMISSION, MODE OF ACTION and SYMPTOMS
COVID-19
HISTORY:
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) The disease was first
identified in 2019 in Wuhan, the capital of Hubei, China,
and has since spread globally, resulting in the 2019–20
coronavirus pandemic.
According to the World Health Organization
(WHO), viral diseases continue to emerge and represent a serious issue to
public health. In the last twenty years, several viral epidemics such as the
severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 to 2003 beginning in China and involving two dozen countries
with approximately 8000 cases and 800 deaths, and H1N1 influenza in
2009, have been recorded. Most recently, the Middle East respiratory syndrome
coronavirus (MERS-CoV) was first identified in Saudi Arabia in 2012 approximately 2,500 cases and 800 deaths.
In a timeline that reaches the present day, an
epidemic of cases with unexplained low respiratory infections detected in
Wuhan, the largest metropolitan area in China's Hubei province, was first
reported to the WHO Country Office in China, on December 31, 2019. Published
literature can trace the beginning of symptomatic individuals back to the beginning
of December 2019. As they were unable to identify the causative agent, these
first cases were classified as "pneumonia of unknown etiology." The
Chinese Center for Disease Control and Prevention (CDC) and local CDCs
organized an intensive outbreak investigation program. The etiology of this
illness is now attributed to a novel virus belonging to the coronavirus (CoV)
family.
Belgian virologist Guido Vanham, the
former head of virology at the Institute for Tropical Medicine in Antwerp,
Belgium, helps answer questions about COVID-19's origins, its behaviour and its
future.
He says that it is certainly a new
virus for human population, it resembles very much with the SARS(2003:it
limited to a few thousand people in several places in the world with the death
rate of about 10%).It relates less closely with another one MERS(It was even
more deadly, it killed one in 3who got infected)But both of these disappeared
following much less drastic measures than theCOVID-19 . ( The differences between the SARS-COV, MERS,
SARS-COV-2 are discussed later)
WHY COVID-19?
On February 11, 2020, the WHO Director-General, Dr. Tedros Adhanom
Ghebreyesus, announced that the disease caused by this new CoV was a
"COVID-19," which is the acronym of "coronavirus disease
2019".
Official names have been announced for the virus responsible for
COVID-19 (previously known as “2019 novel coronavirus”) and the official
name is- severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
This name was chosen because the virus is genetically related to the
coronavirus responsible for the SARS outbreak of 2003.
At first, this virus was
called ‘novel coronavirus’, which means a new strain of coronavirus
(novel=new). Under microscope corona viruses look like a crown. Corona
means crown in Latin, which is how coronaviruses got their name.
Once scientists figured
out exactly what this strain of coronavirus was and how to identify it in
tests, they gave it a name: SARS-CoV-2.
STRUCTURE OF SARS-CoV-2
It is a single positive-sense RNA virus.
Mutation rates of RNA viruses are greater than DNA viruses, suggesting a more
efficient adaptation process for survival. The genome codes for at least four
main structural proteins: spike (S), membrane (M), envelope (E), nucleocapsid
(N) proteins and other accessory proteins which aid the replicative processes
and facilitate entry into cells
SARS-CoV-2 particles are spherical and have proteins called spikes protruding from their surface. These spikes latch onto human cells, then undergo a structural change that allows the viral membrane to fuse with the cell membrane. The viral genes can then enter the host cell to be copied, producing more viruses. Recent work shows that, like the virus that caused the 2002 SARS outbreak, SARS-CoV-2 spikes bind to receptors on the human cell surface called angiotensin-converting enzyme 2 (ACE2).
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Transmission electron microscope image shows
SARS-CoV-2 |
Corona
virus(SARS-COV-2)
4. Mode of spreading:
i) Person-to-person spread
- Between people who are in close
contact with one another (within about 6 feet).
- Through respiratory droplets
produced when an infected person coughs or sneezes.
(Imagine sitting next to someone with
a SARS-CoV-2 infection on the bus or in a meeting room. Suddenly, this person
sneezes or coughs. If they don’t cover their mouth and nose, they could
potentially spray you with respiratory droplets from their nose or mouth. The
droplets that land on you will likely contain the virus. If you then touch your mouth or nose without washing your hands
first, you may accidentally give that virus an entry point into your own body.)
·
These droplets can land in the mouths or noses of people who are nearby or possibly be inhaled into the lungs.
· One recent study suggested that the virus may also be present in feces and could contaminate places like toilet bowls and bathroom sinks. But the researchers noted the possibility of this being a mode of transmission needs more research.
ii) How easily the virus spreads
The virus that causes COVID-19
seems to be spreading easily and sustainably in the community (“community
spread”) in some affected geographic
areas.
Community
spread means people have been infected with the virus in an area,
including some who are not sure how or where they became infected.
iii) Pregnancy and
breastfeeding
The CDC (Centers for disease control and prevention)
currently recommends that mothers with a confirmed case of the virus,
as well as those who may have it, are temporarily separated from their
newborns. This separation helps decrease the risk of transmission.
Women should speak with their healthcare providers about the
benefits and risks of breastfeeding. The CDC hasn’t released any official
guidelines regarding whether women with confirmed or suspected cases should
avoid breastfeeding.
5.Mode of action:
i) Attachment and
Entry
·
The initial attachment of the virion to the host cell is initiated by
interactions between the S protein and its receptor. The sites
of receptor binding domains (RBD) within the S1 region of a coronavirus S
protein vary depending on the virus, with some having the RBD at the N-terminus
of S1 while others (SARS-CoV) have the RBD at the C-terminus of S1.
·
Many α-coronaviruses utilize aminopeptidase N (APN) as their
receptor, SARS-CoV 2 and HCoV-NL63 ( identified in 2004) use angiotensin-converting enzyme 2 (ACE2)
as their receptor and MERS-CoV ( identified in 2012) binds to
dipeptidyl-peptidase 4 (DPP4) to gain entry into human cells.
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·
Cleavage at S2′ exposes a fusion peptide that inserts into
the membrane, which is followed by joining of two heptad repeats in S2 forming
an antiparallel six-helix bundle. The formation of this bundle allows for the
mixing of viral and cellular membranes, resulting in fusion and ultimately
release of the viral genome into the cytoplasm.
ii) Replicase Protein Expression
·
The next step in the
coronavirus lifecycle is the translation
of the replicase gene from the virion genomic RNA. The replicase gene
encodes two large ORFS, rep1a and rep1b, which express two co-terminal
polyproteins, pp1a and pp1ab.
·
In order to express both polyproteins, the virus utilizes a
slippery
sequence
(5′-UUUAAAC-3′) and an RNA pseudoknot that cause ribosomal frameshifting from
the rep1a reading frame into the rep1b ORF.
·
Polyproteins pp1a and pp1ab contain the nsps 1–11 and 1–16,
respectively. In pp1ab, nsp11 from pp1a becomes nsp12 following extension of
pp1a into pp1b. However γ-coronaviruses do not contain a comparable nsp1. These
polyproteins are subsequently cleaved into the individual nsps . Coronaviruses
encode either two or three proteases that cleave the replicase polyproteins.
They are the papain-like proteases (PLpro), encoded within nsp3, and a serine
type protease, the main protease, or Mpro, encoded by nsp5.
·
Next, many of the nsps
assemble into the replicase-transcriptase complex (RTC) to create an
environment suitable for RNA synthesis, and ultimately are responsible for RNA
replication and transcription of the sub-genomic RNAs. The nsps also contain
other enzyme domains and functions, including those important for RNA
replication, for example nsp12 encodes the RNA-dependent RNA polymerase (RdRp)
domain; nsp13 encodes the RNA helicase domain and RNA 5′-triphosphatase
activity; nsp14 encodes the exoribonuclease (ExoN) involved in replication
fidelity and N7-methyltransferase activity; and nsp16 encodes
2′-O-methyltransferase activity.
iii) Replication
and Transcription
·
Viral RNA synthesis follows the translation and
assembly of the viral replicase complexes. Viral RNA synthesis produces both genomic and sub-genomic RNAs.
Sub-genomic RNAs serve as mRNAs for the structural and accessory genes which
reside downstream of the replicase polyproteins. All positive-sense sub-genomic
RNAs are 3′ co-terminal with the full-length viral genome and thus form a set of
nested RNAs, a distinctive property of the order Nidovirales. Both
genomic and sub-genomic RNAs are produced through negative-strand
intermediates. These negative-strand intermediates are only about 1% as
abundant as their positive-sense counterparts and contain both poly-uridylate
and anti-leader sequences .
·
Perhaps the most novel aspect of coronavirus replication is
how the leader and body TRS segments fuse during production of sub-genomic
RNAs. This was originally thought to occur during positive-strand synthesis,
but now it is largely believed to occur during the discontinuous extension of
negative-strand RNA .The current model proposes that the RdRp pauses at any one
of the body TRS sequences (TRS-B); following this pause the RdRp either
continues elongation to the next TRS or it switches to amplifying the leader
sequence at the 5′ end of the genome guided by complementarity of the TRS-B to
the leader TRS (TRS-L). Many pieces of evidence currently support this model,
including the presence of anti-leader sequence at the 3′ end of the
negative-strand sub-genomic RNAs.
iii) Assembly
and Release
·
Following replication
and subgenomic RNA synthesis, the viral
structural proteins, S, E, and M are translated and inserted into the
endoplasmic reticulum (ER). These proteins move along the secretory pathway
into the endoplasmic reticulum-Golgi intermediate compartment (ERGIC). There,
viral genomes encapsidated by N protein bud into membranes of the ERGIC
containing viral structural proteins, forming mature virions .
·
M protein is expressed along with E protein VLPs (virus like
particles) are formed, suggesting these two proteins function together to
produce coronavirus envelopes. N protein
enhances VLP formation, suggesting that fusion of encapsidated genomes into the
ERGIC enhances viral envelopment. The S protein is incorporated into
virions at this step, but is not required for assembly. The ability of the S
protein to traffic to the ERGIC and interact with the M protein is critical for
its incorporation into virions.
·
Some work has
indicated a role for the E protein in inducing membrane curvature, although
others have suggested that E protein prevents the aggregation of M protein. The
E protein may also have a separate role in promoting viral release by altering
the host secretory pathway .
The M protein also binds
to the nucleocapsid, and this interaction promotes the completion of virion assembly. These interactions have been mapped
to the C-terminus of the endodomain of M with CTD 3 of the N-protein .
·
Following assembly, virions are transported to the cell
surface in vesicles and released by exocytosis. It is not known if the virions
use the traditional pathway for transport of large cargo from the Golgi or if
the virus has diverted a separate, unique pathway for its own exit. In several
coronaviruses, S protein that does not get assembled into virions transits to
the cell surface where it mediates cell-cell fusion between infected cells and
adjacent, uninfected cells. This leads to the formation of giant, multinucleated
cells, which allows the virus to spread within an infected organism without
being detected or neutralized by virus-specific antibodies.
6.Symptoms:
Clinical manifestations
Initial presentation — Pneumonia appears to be
the most frequent serious manifestation of infection, characterized primarily
by fever, cough, dyspnea, and bilateral infiltrates on chest imaging.
In a study describing 138 patients with COVID-19 pneumonia in
Wuhan, the most common clinical features at the onset of illness were:
●Fever in 99 percent
●Fatigue in 70 percent
●Anorexia in 40 percent
●Myalgias in 35 percent
●Dyspnea in 31 percent
●Sputum production in 27 percent
In one study, fever was reported in almost all patients, but
approximately 20 percent had a very low grade fever <100.4°F/38°C. In
another study of 1099 patients from Wuhan and other areas in China, fever
(defined as an axillary temperature over 99.5°F/37.5°C) was present in only 44
percent on admission but was ultimately noted in 89 percent during the hospitalization.
Other, less common symptoms have included headache, sore throat,
and rhinorrhea. In addition to respiratory symptoms, gastrointestinal symptoms
(eg, nausea and diarrhea) have also been reported; and in some patients, they
may be the presenting complaint. Acute
respiratory distress syndrome (ARDS) is a major complication in patients with
severe disease. In the study of 138 patients described above, ARDS developed in
20 percent after a median of eight days, and mechanical ventilation was
implemented in 12.3 percent . In another study of 201 hospitalized patients
with COVID-19 in Wuhan, 41 percent developed ARDS; age greater than 65 years,
diabetes mellitus, and hypertension were each associated with ARDS.
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7.Effects of this virus :
·
·
Unfortunately,
the initial symptoms and clinical appearance are not easily distinguishable from other common respiratory infections,
and fever may be absent in older adults. Analysis of both autopsy samples and
experimentally infected animals indicates that the SARSCoV 2 infection in the
lung affects the pneumonic areas and is detected
in type 2 pneumocytes . In tissues SARS-CoV commonly causes diffuse
alveolar damage, bronchial epithelial denudation, loss of cilia and squamous
metaplasia. Giant-cell infiltration, hemophagocytosis and cytomegalic alveolar
pneumocytes were also observed in some cases. The infection progresses through
an inflammatory or exudative phase (characterized by hyaline-membrane formation,
pneumocyte proliferation and edema), a proliferative phase and a fibrotic
phase.
·
The
respiratory tract was the main target of the SARS-CoV, although the
gastrointestinal tract may also be involved. Infection of the central
nervous system has been reported . Symptomatically, SARS generally followed a
triphasic pattern that accompanies each of the phases in tissues. In the first
week after infection, symptoms usually consisted of fever and myalgia. These
early symptoms may have been related to direct viral cytopathic effects, since
increases in viral load could be detected by PCR during this phase of the
disease. Seroconversion was detected during the second week and was followed by
a reduction of viral load.
·
·
Imaging findings — Chest
CT in patients with COVID-19 most commonly demonstrates ground-glass
opacification with or without consolidative abnormalities, consistent with
viral pneumonia . Case series have suggested that chest CT abnormalities are
more likely to be bilateral, have a peripheral distribution, and involve the
lower lobes. Less common findings include pleural thickening, pleural effusion,
and lymphadenopathy.
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| Chest CT |
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