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