COVID-19

Ahsan Misbah-ul-Hadi

MAY 21, 2021

GORDON COLLEGE
[Company address]
Table of Contents
Background ............................................................................................................................................... 2
Introduction .............................................................................................................................................. 2
Symptoms and Transmission of Covid-19 ................................................................................................. 3
Prevention Strategies................................................................................................................................ 3
Epidemiology and Structure of Virus ........................................................................................................ 4
Current Stats and Infection Rates ............................................................................................................. 6
How it infects? .......................................................................................................................................... 7
Quest for Vaccines .................................................................................................................................... 8
References .............................................................................................................................................. 10
Background

Coronavirus originates from the family of viruses that capable of causing illnesses such as
increased body temperature, severe acute respiratory syndrome (SARS) and Middle East
respiratory syndrome (MERS). In 2019, the rapidly spreading virus called the severe acute
respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in central market of Wuhan. The
viral disease was named coronavirus 2019 generally identified as COVID-19.

On December 31, 2019, People Republic of China formally informed the World Health
Organization of the new viral pneumonia disease outbreak in the city of Wuhan, within Hubei
state. The PRC (People's Republic of China) Centre for Disease Control (CDC) analyzed the
respiratory samples and declared that the pneumonia was caused by a novel coronavirus which
named the pneumonia as Novel Coronavirus Pneumonia (NCP)

On January 2, 2020, China’s Ministry of Health alerted all doctors to recognize any case of
pneumonia declaring Wuhan as the epicenter of viral outbreak. Biologists and researchers in China
described the new coronavirus as a cause specific biological agent and released its DNA sequence
to healthcare workers around the globe. On February 11, 2020, WHO announced the official name
for the new coronavirus pandemic: Coronavirus 2019 (COVID-19 ).

Coronaviruses are a family of viruses that can cause respiratory illness in humans. They get their
name, “corona,” from the many crown-like spikes on the surface of the virus. Severe acute
respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the common cold
are examples of coronaviruses that cause illness in humans.

Introduction

COVID-19 is induced by the virus called SARS-CoV-2. The most possible ecological reservoirs
for SARS-CoV-2 are bats. Bats are speculated to be reservoirs of several emerging viruses
including coronaviruses (CoVs). These viruses cause serious disease in humans and agricultural
animals including CoVs that cause severe acute respiratory syndrome SARS (Banerjee et al.,
2019). However, it is also considered that the prime carrier of coronavirus disease, according to
DNA sequence that was discovered in human bodies diagnosed with coronavirus, might have come
from some other host.

Symptoms and Transmission of Covid-19

The major cause of coronavirus is close contact between people. The respiratory droplets, of micro
size, are released into air when an infected person sneezes, coughs and in some rare cases it also
spread when diagnosed individuals talks on close proximity. When these droplets are inhaled or
enter the human body through mouth, eyes or nose they start spreading in new host at rapid rates
and symptoms start to appear in two to fourteen days period. The incubation period for COVID-
19 to be 4·8 days.

The common early symptoms after being infected with coronavirus for Infants, adults and children
alike include high fever, coughing, physical tiredness, sore throat, shortness of breath and diarrhea.
Generally, children infected COVID-19 tend to have mild sickness and fever and seldom need to
be taken to hospital. However, that is not always the case and in couple of reported cases, very
young Children have become severely ill after being infected. Moreover, early symptoms of
coronavirus may include loss of smell and taste. Headaches and continuous chest pain can also be
caused by coronavirus ranging from mild to severe.

Initially mild symptoms appear in people affected by coronavirus and gradually for the people not
given the proper medical aid and treatment, the systems can grow more extreme by a factor of five
to seven times, with cough and shortness of breath worsening if pneumonia further grows. But it
is crucial to remember that the variety and intensity of the initial symptoms will differ widely from
person to person.

Prevention Strategies

At the present moment there are tested vaccine available for COVID-19. And search for single
dose and more potent vaccine is ongoing. Community based treatments, for instance closing of
educational institutes, cancellations of large-scale social events, measures for social distancing,
and organization’s adoption to work from home strategies are having an impact and are aiding in
to minimize the spread of COVID-19. The best prevention strategies for infected individuals
include isolation, social distance and quarantine. Other prevention strategies that can adopted by
communities at large to decrease infection rate are hand sanitization on regular basis, avoiding
unnecessary outdoor activities and remaining indoors, covering mouth while coughing or sneezing
utilization of face masks. Quick cremation and funeral of the bodies of people who have died of
COVID-19 will help prevent individual exposure to the virus.

Epidemiology and Structure of Virus

Coronaviruses possess the largest genomes (26.4–31.7 kb) among all known RNA viruses,
with G + C contents varying from 32% to 43%. Variable numbers of small ORFs are present
between the various conserved genes (ORF1ab, spike, envelope, membrane and nucleocapsid) and,
downstream to the nucleocapsid gene in different coronavirus lineages. The viral genome contains
distinctive features, including a unique N-terminal fragment within the spike protein. Genes for
the major structural proteins in all coronaviruses occur in the 5′–3′ order as S, E, M, and N.

The SARS-CoV-2 is a β-coronavirus, which is enveloped non-segmented positive-sense

RNA virus of subfamily Orthocoronavirinae of the Coronaviridae family. CoVs are divided into
four genera called alpha (α), beta (β), gamma (γ) and delta (δ) CoV. α- and β-CoV can infect
mammals, while γ- and δ-CoV tend to affect birds. 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. Six CoVs have been discovered which can affect human, among
which α-CoVs HCoV-229E and HCoV-NL63, and β-CoVs HCoV-HKU1 and HCoV-OC43 had
low pathogenicity, and cause common cold like milder respiratory symptoms. The other two
known β-CoVs, SARS-CoV, and MERS-CoV lead to severe and fatal respiratory tract infections.
SARS-CoV-2 is 29.9 kb, While SARS-CoV and MERS-CoV have positive-sense RNA genomes
of 27.9 kb and 30.1 kb, respectively. It has been shown that the genome of CoVs contains a variable
number (6-11) of open reading frames (ORFs).

The above figure depicts the structure of the CoVs. CoVs are round or elliptic and often
pleomorphic form, with a diameter of approximately 60–140 nm. The single-stranded RNA
genome contains 29891 nucleotides, encoding for 9860 amino acids. Two-thirds of viral RNA,
mainly located in the first open reading frame (ORF 1a/b), encodes 16 non-structure proteins
(NSPs). The rest part of the virus genome encodes four essential structural proteins, including
spike (S) glycoprotein, small envelope (E) protein, matrix (M) protein, and nucleocapsid (N)
protein, and also several accessory proteins that interfere with host immune response. The primary
functions that direct coronavirus RNA synthesis and processing reside in nonstructural protein
(nsp) 7 to 16, which are cleavage products of two large replicase polyproteins translated from the
coronavirus genome.

The sequencing studies revealed genomic and phylogenetic similarity of the SARS-CoV-
2 with SARS-CoV, particularly in the S-protein gene and the receptor binding domain (RBD).
This indicated the capability of direct human transmission like SARS-CoV. The whole-genome
sequence studies showed that COVID-19 appears closer to the SARS-like bat CoVs as compared
to the known SARS-CoV and MERS-CoV. It has been proven that the genome of the new HCoV,
isolated from a cluster-patient with atypical pneumonia after visiting Wuhan, had 89% nucleotide
identity with bat SARS-like-CoVZXC21 and 82% with that of human SARS-CoV. For this reason,
the new virus was called SARS-CoV-2.[59] The majority of genomically encoded proteins of
SARS CoV-2 and SARS-CoVs were similar, except few differences in some amino acid
substitutions in NSP2, NSP3, spike protein and receptor binding domains.

Another recent research suggested that the mutation in NSP2 and NSP3 play a role in
infectious capability and differentiation mechanism of COVID-19. A study revealed that SARS
CoV-2 was mutating in different patients in China. Tang conducted a population genetic analysis
of 103 COVID-19 genomes and classified out two prevalent types of COVID, L type
(approximately 70%) and S type (approximately 30%). The strains in L type, derived from S type,
are evolutionarily more aggressive and contagious. There is a need to keep an eye over this novel
CoVs for their virulence and epidemic spread over the globe, at present.

It was also found that the genome sequence of SARS-CoV-2 is 96.2% identical to a bat
CoV RaTG13, whereas it shares 79.5% identity to SARS-CoV. Based on virus genome sequencing
results and evolutionary analysis, the bat is suspected as the natural host of virus origin, and
COVID-19 might be transmitted from bats via unknown intermediate hosts like pangolins, other
reptiles, and snakes etc., to infect humans.

Current Stats and Infection Rates

The number of people infected changes daily. Organizations that collect this information,
including the World Health Organization (WHO) and the Centers for Disease Control and
Prevention (CDC), are gathering information and continuously learning more about this outbreak.
As of this writing (05/11/2021), more than 159,000,000 people in the world have been infected.
Over 3,300,000 people have died. Some 192 countries and territories on all continents (except
Antarctica) have now reported cases of COVID-19. The U.S. has the highest number of cases, with
more than 32,000,000 people infected and over 580,000 deaths. India has nearly 23,000,000 cases
and 250,000 deaths. Brazil has more than 15,200,000 cases and 420,000 deaths. France has over
5,800,000 cases; Turkey has over 5,000,000 cases; Russia and England have over 4,400,000 cases;
Italy has more than 4,100,000; Spain and Germany have over 3,500,000 cases; Argentina and
Columbia have more than 3,000,000 cases; Poland and Iran have over 2,600,000 cases and Mexico
has over 2,300,000 cases.

How it infects?

COVID-19 is likely spread when the virus travels in respiratory droplets when an infected
person coughs, sneezes, talks, sings or breathes near you (within six feet). This is thought to be the
main way COVID-19 is spread. It can also spread when the virus travels in small respiratory
droplets that linger in the air for minutes to hours from an infected person who is more than six
feet away or has since left the space. This method of spread is more likely to occur in enclosed
spaces with poor ventilation. It spreads from close contact (touching, shaking hands) with an
infected person and also by touching surfaces that the virus has landed on, then touching your eyes,
mouth, or nose before washing your hands.

COVID-19 enters the body through your mouth, nose or eyes (directly from the airborne
droplets or from transfer of the virus from your hands to your face). The virus travels to the back
of your nasal passages and mucous membrane in the back of your throat. It attaches to cells there,
begins to multiply and moves into lung tissue. From there, the virus can spread to other body
tissues.
Quest for Vaccines
There has been an intensive search for an effective drug against the virus or the resultant
disease and has not led to any breakthrough agents. Few drugs namely hydroxychloroquine and
remdesivir have been advocated as desperate measures to fight COVID-19 based on a few
preliminary, contradictory, and inconclusive studies. What we need is a drug that is at least 95%
effective to stop the pandemic. These and other drugs may save lives but are nowhere near that
power to bring normalcy in the utter chaos caused by the pandemic. This leaves us with only one
choice namely an effective and safe vaccine that shall be manufactured as soon as possible and
available to all countries and populations affected by the pandemic at an affordable price.

A vaccine has the power to generate herd immunity in the communities, which will reduce
the incidence of disease, block transmission, and reduce the social and economic burden of the
disease. Very high immunization coverage can effectively fight the pandemic, prevent secondary
waves of infection, and control the seasonal endemic infection outbursts. Eventually, the disease
can be eradicated as has happened in many other diseases that have had even with higher potential
than COVID-19 to cause pandemics namely smallpox, poliomyelitis, etc.

A vaccine is medical preparations ranging from intact organisms (attenuated live or

inactivated) to genetically engineered parts of the organisms (antigenic) that induce both arms of
the adaptive immune system and stimulate a sufficient number of memory T cells and B
lymphocytes. Vaccines should contain antigens necessary to mount the specific response without
causing disease. Once challenged with the pathogen, memory cells yield effector T cells and
antibody-producing B cells and fight the infection. The antibodies have to be the neutralizing type
which binds to the virus and block infection. The virus coated with neutralizing antibodies either
cannot interact with the receptor or may be unable to uncoated of the genome. Most currently
licensed vaccines induce neutralizing antibody responses capable of mediating long-term
protection against lytic viruses such as influenza and smallpox. The T cell–based responses that
recognize and kill infected cells do also fight the infection. Following antigen processing in
dendritic cells, the small peptides are displayed at the cell surface at the groove of major
histocompatibility complex (MHC) class I and class II molecules. Cytotoxic T cells (CD8+)
recognize MHC class I-peptide complexes and differentiate into cytotoxic effector cells capable
of killing infected cells or pathogens. Helper T cells (CD4+) recognize MHC class II-peptide
complexes and differentiate in effector cells that produce preferentially T helper 1 cells (Th1) or
T helper cells 2 (Th2) cytokines (Figure 1). Th1 support CD8+ T cell differentiation, which is in
contrast inhibited by Th2-like cytokines. Vaccines against chronic pathogens namely
Mycobacterium tuberculosis, malaria, HCV, HIV, etc. more often require cell-mediated immune
responses to control the infection.

Figure 1 Schematic drawing of 8 platform strategies used for the development of COVID-19 vaccines, and the pathway
each one follows to induce T cell and B cell immune response. The strategies include live-attenuated vaccine (LA),
inactivated vaccine (IA), DNA vaccine (DNA), RNA vaccine (RNA), viral vector replicating vaccine (VVR), viral vector
nonreplicating (VVNR), virus-like particles (VLP), and subunit vaccine (Subunit). CV, coronavirus; APC, antigen
processing cell.
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