Abstract
In the last two years, SARS-CoV-2 infection, commonly called COVID-19,
has taken a jump from being rarely talked about to becoming a household
name. Making it to history as the 5th global pandemic,
this public health crisis has taken millions of lives all over the
world. Right from the time of identification of patient zero, the
pandemic has been a series of waves of infection, causing a domino
effect whose impact has been felt in all walks of life. Global efforts
have been underway to combat this pandemic and minimize its
repercussions, resulting in the development of efficient vaccines and
drugs to control and treat the disease. However, making the benefits of
these efforts available to everyone and walking the path towards the end
of the pandemic remains a challenge. Keeping this in view, this review
intends to present aspects of sequential development of the pandemic,
different types of variants, risks associated with different categories
of people, drugs currently in use, recent advancements in diagnostics
and treatment, and the challenges that continue to remain in overcoming
this pandemic. However, the task of controlling and managing the impact
of such a massive pandemic goes well beyond the boundaries of what
present-day technology in the field of medicine and health-care can
offer. A collaborative and integrative approach between academic,
scientific, social, and economic factors, along with close supervision
and reinforcement of the current public safety protocols, can help to
ensure a better management strategy to control the progression of
COVID-19.
KEYWORDS: Challenges, COVID-19, SARS-CoV-2, Risks, Vaccines,
Varriants
Abbreviations:
3CLpro,3 chymotrypsin-like protease; ACE-2,angiotensin converting
enzyme; APEE, Agrimonia pilosa ethanol extract; CDC, centers for disease
control and prevention; EC50,effective concentration; EGCG,
Epigallocatechin gallate; ICU, Intensive care unit; MERS, Middle East
respiratory syndrome; Mpro, main protease; PLpro, Papain-Like Protease;
PPE, personal protective equipment; RdRp, RNA-dependent RNA Polymerase;
RDV-TP, remdesivir triphosphate; SARS, Severe acute respiratory
syndrome; ssRNA, single stranded RNA; WHO- world health organization
INTRODUCTION
Novel coronavirus (2019-nCoV) began in December 2019 when many
unidentified pneumonia cases were appearing in Wuhan city in the Hubei
Province of China. As time went on, this virus continued to spread not
only in China but the entire world. On January 30th,
2020 the World Health Organization declared a public health emergency of
international importance, and a few weeks later on March
11th, 2020, they declared this as a global pandemic
naming the disease as coronavirus disease 2019 or COVID- 19 . Later on,
it was renamed as Severe Acute Respiratory Syndrome Coronavirus 2 or
SARS-CoV-2 by the Coronaviridae Study Group of the International
Committee on Taxonomy of Viruses .
SARS-CoV-2, belongs to the family Coronaviridae and the genus
betacoronavirus. Severe acute respiratory syndrome (SARS) and the Middle
East Respiratory Syndrome (MERS) also belong to the same family. It
appears from viral genome analysis that SARS-CoV-2 is a recombinant
virus between the bat coronavirus and an unknown origin coronavirus .
These viruses are seen to have a positive sense of single-stranded RNA
(ssRNA) which is enveloped by a helical symmetry nucleocapsid . The
peplomers or the trimeric spike glycoproteins which give the virus its
corona-like appearance allow the virus to enter the host cell and is
seen to infect mainly humans, mammals, and birds .
COVID-19 is highly transmissible and rapidly spreads from human to human
via respiratory droplets from cough or sneeze and also through in-person
contact. This makes it highly susceptible to mutations and recombination
causing it to be very diverse and difficult to control and manage.
Common symptoms seen in affected patients are fever, cough, sore throat,
fatigue, headache, shortness of breath, loss of sense of smell and
taste, phlegm production, and chills ). However, many individuals do
remain asymptomatic which adds yet another challenge to control the
disease.
Since the first appearance, this disease has been a global concern that
the world has collectively been combating together. It has been rapidly
spreading and many people have been affected by this disease with both
minor and major complications including deaths. Therefore, it is vital
to have a comprehensive understanding of all the possible routes for the
control and management of COVID-19. In this article, we have reviewed
various advances in the diagnosis, treatment, and management of COVID-19
along with their risks and challenges to provide an update, two and a
half years after the pandemic has begun.
GLOBAL EPIDEMIOLOGY
For a severely contagious disease like COVID-19 that has taken millions
of lives across the globe, it becomes of utmost importance to understand
the source, causes, and distribution of the disease. In addition, it is
important to analyze the fine interplay between political, social, and
scientific elements that could worsen the disease risk and provide a
better understanding of different measures that can be undertaken to
control and manage the pandemic. The pattern of infection of the virus
across various geographical regions has been ever-changing with the
different waves of the pandemic. The different variants of the virus
emerging as a result of frequent mutations have also posed a challenge
in managing the pandemic. Some of the worst affected regions as of 21st
May 2020 during the first wave include the United States of America,
followed by Brazil, the United Kingdom, Spain, Italy, France, and China
. The first wave of COVID-19 appears to have majorly affected people of
over 30 years, followed by those belonging to the 20-24 years age group,
and finally the 0 –19 years age group . The second wave was most
devastating and the top countries affected during this wave include,
United States, India, Brazil, Russia, France, Italy, the UK, Spain, and
Argentina. The third wave which began in late 2021 infected a large
population and people over the age of 30 were worst affected, following
a pattern similar to that of the first wave . The third wave now appears
to be ongoing in many countries seeing a surge in the number of active
cases again. The number of active cases and deaths as of 14th January
2022, in different regions of the world, is summarized in Table
1 .
VARIANTS OF SARS-COV-2
COVID-19 is a rapidly spreading virus that widely circulates among the
population increases the chances of mutation. With the increase in the
spread of the virus, there is a higher chance of changes in its
structure and genetic composition creating an additional matter of
concern. Moreover, these viral mutations don’t alter the way the virus
works therefore not necessarily affecting the ability of the virus to
induce the diseased state in the host . However, depending upon the
exact location of the change in the genetic material it can alter the
transmission capability as well as the severity of the disease. These
mutations have led to the formation of different variants.
Different genetic variations of SARS-CoV-2have been reported during the
COVID-19 pandemic and their structural variations as created a great
concern globally. Countries around the world are struggling with
successive new waves of infections due to these different variants. The
variants arise through viral replication naturally and can affect vital
pathogenic components of the virus, like the receptor-binding domain of
the spike protein . The variants which are associated with an increase
in transmissibility and virulence can cause some change in the clinical
symptoms presented, or reduce the efficacy of available treatments and
are termed as variants of concern (VOCs) . The most commonly reported
variants with their structural variations are shown in Figure
1 . The different variants and their representative characteristics are
summarized in Table 2 .
CURRENT ADVANCES IN DIAGNOSIS AND TREATMENT