AREVIEW OF COVID-19 IDENTIFICATION, CLASSI-FICATION, THERAPY, PREVENTION AND VACCINATION

AREVIEW OF COVID-19 IDENTIFICATION, CLASSI-FICATION, THERAPY, PREVENTION AND VACCINATION

Najmeen Nisha *, Neda Fatima, Hira Moid and Anil Kumar

Dr. Shakuntala Mishra National Rehabilitation University, Mohan Rd, Lucknow, Uttar Pradesh, India.

ABSTRACT: The population is currently under threat from a new global health emergency called COVID-19 (Coronavirus Disease-2019). The World Health Organization has classified the virus epidemic as a public health emergency of international concern since December 2019, when COVID-19 first surfaced at a seafood market in Wuhan, South China, and spread quickly throughout the world (WHO). In order to inform potential COVID-19 patients about COVID-19 prevention, diagnosis, treatments, and prevention, we have summarized the most recent clinical characteristic data below. We gathered information for this evaluation from a number of research reports, WHO recommendations, and other articles. It is crucial to remind readers that new information on clinical traits, diagnoses, treatment plans, and outcomes for COVID-19 is updated almost hourly. The ailment has affected people to varied degrees all across the world. The patient displays a variety of symptoms, most frequently a fever, cough, sore throat, shortness of breath, exhaustion and malaise. The condition is treated with general care, symptomatic care, antiviral medication, oxygen therapy and the immune system. To limit the potential spread of infection to other patients and medical personnel, it is essential to detect probable cases as soon as feasible and to isolate the suspected cases from the confirmed COVID-19 cases.

Keywords: Coronavirus, Prevention, Diagnosis, Treatment, Antiviral, Immune system

INTRODUCTION: The word "coronavirus" comes from the Latin corona, which is a derivation from the Greek v korn, which means "garland, wreath." When June Almeida and David Tyrrell discovered and researched human coronaviruses, they came up with the term. An unofficial group of virologists initially coined the term to describe the new family of viruses in the journal Nature in 1968.

The term is a reference to the virions' distinctive appearance under electron microscopy, which is characterized by a fringe of enormous, bulbous surface projections that resembles the solar corona or halo. The viral spike peplomers, which are proteins on the surface of the virus, produce this shape ¹.

The first COVID-19 incident was observed. In Wuhan, China, a well-known seafood market where many people come to buy or trade seafood, 27 COVID-19 pneumonia cases were recorded by the WMHC (Wuhan Municipal Health Commission) as of December 31 ². The International Committee for the Nomenclature of Viruses (later renamed the International Committee on Taxonomy of Viruses) approved the scientific name Coronavirus as a genus name in 1971 ³. Large, approximately spherical particles with distinctive surface projections are coronaviruses. They have a wide variation in size, often between 80 and 120 nm in diameter. Extreme sizes between 50 and 200 nm in diameter are known. The typical molecular weight is 40,000 kDa. They are contained in a package that contains several protein molecules ⁴. When the virus is outside the host cell, it is shielded by the lipid bilayer envelope, membrane proteins, and nucleocapsid ⁵. The membrane (M), envelope (E), and spike (S) structural proteins are embedded in a lipid bilayer that makes up the viral envelope ⁶. The lipid bilayer and the structural proteins E and M work together to shape and preserve the size of the viral envelope. In order to connect with the host cells, S proteins are required. The M protein of the human coronavirus NL63, as opposed to the S protein, has the binding site for the host cell. The envelope has an 85-nm diameter. In electron micrographs, the virus's envelope is seen as a discrete pair of electron-dense shells (shells that are relatively opaque to the electron beam used to scan the virus particle) ⁷. The M protein, a type III membrane protein, is the primary structural protein of the envelope and gives it its overall form. It creates a layer that is 7.8 nm thick and is made up of residues of 218 to 263 amino acids. A short N-terminal ectodomain, a triple-spanning transmembrane domain, and a C-terminal endodomain make up its three domains. The C-terminal domain creates a lattice-like structure that increases the envelope's additional thickness. The amino-terminal region of a protein may contain either N- or O-linked glycans, depending on the species. The assembly, budding, envelope formation, and pathogenic phases of the virus lifecycle depend on the M protein ⁸.

FIG. 1: ILLUSTRATION OF SARS-COV-2, THE VIRUS THAT CAUSES COVID-19 ⁸. Blue: lipid bilayer envelope, Light blue: spike (S) glycoprotein, Red: envelope (E) proteins, Green: membrane (M) proteins, Orange: glycan.

A new human coronavirus illness since the 1918 flu pandemic, COVID-19, has been identified as the fifth pandemic. After being first discovered in Wuhan, China, COVID-19 quickly spread throughout the world. Based on a phylogenetic study, the coronavirus was given the name severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. SARS-CoV-2 is thought to have evolved from an animal coronavirus through spillover and later picked up the capacity for human-to-human transmission. The virus spreads quickly among humans and is constantly evolving since it is so contagious. We analyze the fundamental characteristics, conceivable origin, and evolutionary history of the novel human coronavirus in this review article. The development of vaccines against the virus and research on pathogenicity may both depend on these elements ⁹.

FIG. 2: A TIMELINE OF FIVE PANDEMICS SINCE 1918 AND THE GLOBALLY CIRCULATING VIRUSES AFTERWARD ⁹

The fifth pandemic after the 1918 flu pandemic, coronavirus disease 2019 (COVID-19), is currently affecting individuals all over the world. Since late December 2019, we have been able to trace the first complaint and subsequent epidemic to a cluster of unique human pneumonia cases in Wuhan City, China. The earliest symptomatic date was December 1, 2019. Viral pneumonia was diagnosed based on these individuals' symptomatology, which included fever, lethargy, dry cough, and dyspnea ¹⁰. Because of the location and the symptoms of pneumonia, the disease was initially referred to as Wuhan pneumonia by the media. A new coronavirus was identified as the cause by whole-genome sequencing data. Consequently, this virus is the eighth coronavirus family member to infect humans ¹¹.

The World Health Organization (WHO) initially called the new virus 2019 novel coronavirus (2019-nCoV) on January 12, 2020, and coronavirus illness 2019 (COVID-19) on February 12, 2020, respectively. Later, the virus was officially designated SARS-CoV-2 by the International Committee on Taxonomy of Viruses (ICTV) based on phylogeny, taxonomy, and accepted practice ¹². Humans contract common colds from coronaviruses (CoV), which are also to blame for the Middle East and Severe Acute Respiratory Syndromes (SARS and MERS, respectively). Live attenuated vaccines (LAVs), some of which target the envelope (E) protein, a tiny membrane protein that creates ion channels, are a promising method of prophylaxis. Unfortunately, SARS-CoV E still has very little information, and other CoV E proteins have no precise structural information. Here, we present a structural model of a SARS-CoV E construct in LMPG micelles that contains clear intermolecular NOEs for the first time. The model for the detergent-embedded area agrees with orientational restrictions previously discovered in lipid bilayers and in-vivo escape mutants. The majority of the C-terminal domain is helical, and extramembrane intermolecular NOEs point to interactions that could influence the conformation of the TM channel ¹³.

CoVs were named after a viral particle with an envelope that resembles a crown. The CoV genome is the second-largest RNA virus genome and is a positive-sense, single-strand RNA (+ssRNA) with a size of 27–32 kb. Normally, two major overlapping polyproteins, ORF1a and ORF1b, which are processed into the viral polymerase (RdRp) and other nonstructural proteins involved in RNA synthesis or host response modulation, are encoded by two thirds of the genomic RNA. Four structural proteins (spike (S), envelope (E), membrane (M), and nucleocapsid (N)) and additional accessory proteins are encoded in the remaining part of the genome. The ORF1a/ORF1b and the four structural proteins are rather stable. However, the size and quantity of accessory proteins strongly influence the length of the CoV genome ¹⁴. There are four primary structural proteins found in coronavirus particles. These are the proteins that are encoded at the 3′ end of the viral genome: the spike (S), membrane (M), envelope (E), and nucleocapsid (N). The 150 kDa S protein is extensively N-linked glycosylated and uses an N-terminal signal sequence to enter the ER. The unique spike structure on the surface of the virus is made up of homotrimers of the S protein expressed by virus ¹⁵. A class I fusion protein is the trimeric S glycoprotein ¹⁶. And facilitates a host receptor's adhesion ¹⁷. In the majority of coronaviruses, S is split into two distinct polypeptides called S1 and S2 by a host cell furin-like protease. S2 makes up the stalk of the spike molecule, whereas S1 makes up the major receptor-binding domain of the S protein ¹⁸.

The M protein dominates the virion's structural protein composition. It is a Scientific term protein (about 25–30 kDa) with three transmembrane domains that is hypothesized to form the virion. Its C-terminal endodomain extends 6–8 nm inside the viral particle and possesses a significantly bigger N-terminal glycosylated ectodomain ¹⁹. Most M proteins lack a signal sequence despite being co-translationally placed in the ER membrane. According to recent research, the M protein may exist as a dimer in the virion and may take on two distinct conformations that enable it to bind to the nucleocapsid and enhance membrane curvature ⁵.

The virion contains trace amounts of the E protein (8–12 kDa). Despite their significant divergence, the coronavirus E proteins share a similar design ²⁰. Although the E protein's membrane topology is not entirely clear, the majority of the available data points to it being a transmembrane protein. The E protein functions as an ion channel and has an N- and C-terminal ectodomain. Recombinant viruses lacking the E protein are not invariably fatal, in contrast to other structural proteins, however, virus type affects this ²¹. The E protein helps the virus assemble and spread, but it also serves other purposes. For instance, the SARS-CoV E protein's ion channel function is needed for pathogenesis but not for viral replication ²².

The nucleocapsid contains solely the N protein as its protein. It is made up of two distinct domains, an N-terminal domain (NTD) and a C-terminal domain (CTD), both of which can bind RNA in vitro using various processes. It has been proposed that both domains are necessary for efficient RNA binding ²³. The N protein is also extensively phosphorylated, and it has been proposed that phosphorylation causes a structural alteration that increases the affinity for viral RNA as opposed to nonviral RNA. The N protein forms a conformation resembling beads on a string to bind the viral DNA. The genomic packing signal and the TRSs have been identified as two of the N protein's distinct RNA substrates ²⁴. It has been discovered that the genomic packing signal binds selectively to the second, or C-terminal, RNA binding domain. Additionally, the M protein and nsp3, a crucial part of the replicase complex, are bound by the N protein. These protein interactions probably aid in binding the viral DNA to the RTC and packaging the encapsulated genome into viral particles ²⁵.

General Classification of Human Coronaviruses: Coronaviruses (CoVs) are positive-sensed single-stranded RNA viruses (ssRNA) encased in an envelope. They are members of the family Coronaviridae in the order Nidovirales. The word "Corona," which means "crown" in Latin, refers to the spike proteins that give the virus its distinctive crown-like appearance and enable it to engage with host cell receptors, a crucial stage in the process of penetrating the host cell membrane.

Based on differences in the protein sequence, this group of viruses is split into four genera: There are four different types of coronaviruses: alpha, beta, gamma, and delta ²⁶. Seven different coronavirus strains, including the alpha- and beta-coronaviruses HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2, are known to infect people. Human coronavirus is abbreviated as HCoV; alpha-CoVs include HCoV-229E and HCoV-NL63, whereas beta-CoVs include HCoV-OC43 and HCoV-HKU1. The stomach flu, severe rhinitis, or common cold infections that result in diarrhea are only a few of the minor symptoms that these human coronaviruses typically produce ²⁷.

FIG. 3: CLASSIFICATION OF HUMAN CORONA-VIRUSES, SARS-COV, MERS-COV, AND SARS-COV-2 ²⁴

SARS-CoV, MERS-CoV and SARS-CoV-2, which are beta-CoVs, on the other hand are very contagious and pathogenic, increasing the risk that patients will contract severe acute respiratory infections such as pneumonia. SARS-CoV and MERS-CoV are zoonotic diseases that can be spread from animal to human during intimate contact, according to epidemiological evidence. It was discovered in 2002 that the SARS-CoV outbreak in Guangdong Province, China, was brought on by a bat-to-human transmission route using civet cats as the intermediary host. Ten years later, in 2012, it was determined that people and camels were the sources of the Middle East respiratory syndrome (MERS) outbreak caused by MERS-CoV from Saudi Arabia ²⁸.

In China's Hubei Province, Wuhan, saw an outbreak of an unnamed pneumonia sickness in December 2019 that was brought on by a new coronavirus (nCoV) ²⁹. The novel coronavirus strain, which hasn't been discovered in people before, is known by the provisional designation nCoV. Prior to being given the name severe acute respiratory syndrome coronavirus 2 (SAR-CoV-2) by the International Committee on Taxonomy of Viruses, this novel strain of the virus was known as 2019-nCoV (ICTV) ²⁵. As of July 1, 2022, there were more than 545 million verified COVID-19 cases, including more than 6 million fatalities, according to the WHO. There were formerly four SARS-CoV-2 variants of concern (VOC): Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2). However, on November 26, 2021, the WHO identified the Omicron variation, a new variety of concern that was initially revealed by experts in South Africa (B.1.1.529). Omicron is now the most common form in circulation worldwide as a result. These are brought on by mutations, particularly those that affect the spike protein's receptor-binding domain (RBD), which promotes viral replication in the upper respiratory tract and in-vivo transmission ³⁰.

Replication Cycle:

Cell Entry: When the viral spike protein binds to the complementary host cell receptor, infection starts. The host cell's protease cleaves and activates the receptor-attached spike protein after attachment. Cleavage and activation enable the virus to enter the host cell via endocytosis or direct fusing of the viral envelope with the host membrane depending on the kind of host cell protease present ³¹.  Contacts between the S protein and its receptor start the initial attachment of the virion to the host cell. Different coronaviruses have different locations for their receptor binding domains (RBD), with some having them at the N-terminus of S1 (MHV), while others (SARS-CoV) have them at the C-terminus of S1 ³².

The S-protein-receptor interaction is the key factor in coronavirus infection of a host species and controls the virus's tissue tropism. Peptidase is used by many coronaviruses as their cellular receptor. Given that entrance happens even when these proteins' enzymatic domains are absent, it is unclear why peptidases are used. Many coronaviruses bind to aminopeptidase N (APN), SARS-CoV and HCoV-NL63 bind to angiotensin-converting enzyme 2 (ACE2), MHV enters through CEACAM1, and the recently discovered MERS-CoV binds to dipeptidyl-peptidase 4 (DPP4) to enter human cells ³³. Aminopeptidase N (APN), ACE2 (angiotensin-converting enzyme 2), DPP4 (dipeptidyl peptidase 4), mCEACAM (murine carcinoembryonic antigen-related adhesion molecule 1), TGEV (transmissible gastroenteritis virus), and PEDV (porcine epidemic diarrhea virus) are some examples of viruses; MHV (murine hepatitis virus), CCoV (canine coronavirus), BCoV (bvine coronavirus), FIPV (feline infectious peritonitis virus), the coronaviruses responsible for SARS and MERS are both severe acute respiratory syndrome viruses ³³.

Genome Translation: The non-segmented, 30-kb positive-sense RNA genome of coronaviruses is non-translated. The genome functions as an mRNA for the translation of the replicase polyproteins because it has a 5′ cap structure and a 3′ poly (A) tail. Contrary to the structural and accessory proteins, which make up only approximately 10 kb of the viral genome, the replicase gene for the non-structural proteins (nsps) takes up around two-thirds of the genome, or about 20 kb. A leader sequence and an untranslated region (UTR) with numerous stem loop structures necessary for RNA replication and transcription can be found near the 5′ end of the genome. Transcriptional regulatory sequences (TRSs), which are necessary for the expression of each of these genes, are also present at the start of each structural or auxiliary gene. RNA structures needed for viral RNA production and replication are also present in the 3′ UTR. The coronavirus genome is structured as a 5′-leader-UTR-replicase. At the 3′ end of the genome, there are structural genes with a 3′ UTR-poly (A) tail and auxiliary genes scattered throughout. In tissue culture, accessory proteins are almost entirely non-essential for replication, although several have been found to play crucial roles in viral pathogenesis ³⁴.

FIG. 4: GENOMIC ORGANIZATION OF REPRESENTATIVE Α, Β, AND Γ COVS. THE TOP OF THE IMAGE SHOWS A REPRESENTATION OF THE MHV GENOME. THE STRUCTURAL AND AUXILIARY PROTEINS IN THE 3′ SECTIONS OF THE HCOV-229E, MHV, SARS-COV, MERS-COV, AND IBV ARE VISIBLE IN THE PORTIONS BELOW THAT HAVE BEEN ENLARGED. SIZE OF THE GENOME AND INDIVIDUAL GENES ARE APPROXIMATED USING THE LEGEND AT THE TOP OF THE DIAGRAM BUT ARE NOT DRAWN TO SCALE. HUMAN CORONAVIRUS 229E (HCOV-229E), MOUSE HEPATITIS VIRUS (MHV), SEVERE ACUTE RESPIRATORY SYNDROME (SARS-COV), MIDDLE EAST RESPIRATORY SYNDROME (MERS-COV), AND INFECTIOUS BRONCHITIS VIRUS (IBV) ARE SOME EXAMPLES OF CORONAVIRUSES ³²

Replicase-transcriptase: A multi-protein replicase-transcriptase complex is created when a number of the non-structural proteins come together (RTC). The RNA-dependent RNA polymerase (RdRp) is the primary protein involved in replicase transcription. It participates directly in the transcription and replication of RNA from an RNA strand.

The complex's other non-structural proteins contribute to the processes of transcription and replication. For example, the exoribonuclease non-structural protein increases replication fidelity by performing a proofreading role that the RNA-dependent RNA polymerase is unable to do ³⁵.

Replication: The translation of the replicase gene from the virion genomic RNA is the next phase in the coronavirus lifecycle. The replicase gene produces two co-terminal polyproteins, pp1a and pp1ab, by encoding two big ORFs, rep1a and rep1b.

The virus uses a slippery sequence (5′-UUUAAAC-3′) and an RNA pseudoknot to drive ribosomal frameshifting from the rep1a reading frame into the rep1b ORF in order to express both polyproteins. The ribosome typically unravels the pseudoknot structure and carries on translating until it comes across the rep1a stop codon. Sometimes the pseudoknot prevents the ribosome from extending translation into rep1b, forcing it to stall on the slippery sequence and move the reading frame back one nucleotide, or a -1 frameshift, before the ribosome is able to melt the pseudoknot structure and extend translation into pp1ab ³⁶. Ribosomal frameshifting may occur up to 25% of the time, according to in-vitro research; however, this hasn't been confirmed in relation to viral infection. Although the precise purpose of these viruses' use of frameshifting to regulate protein expression is unknown, it is believed to be either to precisely regulate the ratio of rep1b to rep1a proteins or to postpone the production of rep1b until the environment for RNA replication has been sufficiently prepared by rep1a's products ³⁷.

FIG. 5: REPLICATION COMPLEX OF RNA³⁸

After that, a large number of NSPS come together to form the replicase-transcriptase complex (RTC), which is ultimately in charge of RNA replication and transcription of the sub-genomic RNAs. Other enzyme domains and activities, such as those necessary for RNA replication, are also encoded by the NSPS. For instance, 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: Some of the NSPS have been found to perform additional actions outside replication, such as suppressing innate immunological responses (nsp1; nsp16-2′-O-methyl transferase; nsp3-deubiquitinase), while others have completely unidentified roles (nsp3-ADP-ribose-1′′-phosphatase; nuclease (Nendo). Non-structural proteins and their envisioned uses. Interestingly, the Nidovirales order is the only one that has the ribonucleases nsp15-NendoU and nsp14-ExoN activities, which are regarded as genetic identifiers for these viruses ³⁹.

TABLE 1: FUNCTIONS OF CORONAVIRUS NON-STRUCTURAL PROTEINS (NSPS)

Transcription: Viral replicase complexes are assembled and translated before being translated into viral RNA. Genomic and sub-genomic RNAs are both produced during viral RNA production. The structural and auxiliary genes located downstream of the replicase polyproteins are transcribed into messenger RNAs (mRNAs) by sub-genomic RNAs. A distinguishing characteristic of the order Nidovirales is that all positive-sense sub-genomic RNAs are 3′ co-terminal with the full-length viral genome and so constitute a set of nested RNAs. Negative-strand intermediates are used to create both genomic and sub-genomic RNAs. These poly-uridylate and anti-leader sequence-containing negative-strand intermediates are just 1% as prevalent as their positive-sense counterparts ⁴⁰. It takes a lot of cis-acting sequences for viral RNAs to replicate. Seven stem-loop structures that may extend into the replicase 1a gene can be found in the genome's 5′ UTR ⁴¹. Transcription of the viral genome is the complex's additional significant function. RdRp directly mediates the conversion of positive-sense genomic RNA into negative-sense subgenomic RNA molecules. The transcription of these negative-sense subgenomic RNA molecules into their corresponding positive-sense mRNAs occurs after this step. The "nested set" of subgenomic mRNAs has a shared 5'-head and a largely duplicated 3'-end ⁴².

FIG. 6: EAV REPLICATION AND TRANSCRIPTION MODEL. CONTINUOUS MINUS-STRAND RNA SYNTHESIS, WHICH NSP1 IS NOT REQUIRED FOR, PRODUCES A GENOME-LENGTH NEGATIVE STRAND TEMPLATE FOR GENOME REPLICATION. A NESTED COLLECTION OF SUB GENOME-LENGTH MINUS STRANDS PRODUCED BY DISCONTINUOUS MINUS-STRAND RNA SYNTHESIS ACT AS TEMPLATES FOR THE PRODUCTION OF SG MRNA. NSP1 IS ESSENTIAL FOR THIS PROCESS, WHICH IS ALSO CONTROLLED BY A BASE PAIRING INTERACTION BETWEEN THE GENOMIC LEADER TRS, CONTAINED IN AN RNA HAIRPIN STRUCTURE (LTH), AND THE TRS COMPLEMENT [() TRS] AT THE 3′ END OF THE DEVELOPING MINUS-STRAND ⁴³

Recombination: When at least two viral genomes are present in the same infected cell, the replicase-transcriptase complex is also capable of genetic recombination. When it comes to the genetic diversity within a coronavirus species, the ability of a coronavirus species to jump from one host to another, sporadically, the formation of novel coronaviruses, RNA recombination appears to be a primary driving force. Although the precise mechanism of recombination in coronaviruses is unknown, template swapping probably occurs during genome replication ⁴⁴.

Assembly and Release: Membranes are where virion assembly occurs. N protein binds to genomic RNA, which then connects with M protein and buds into the ER and Golgi membranes. M is assumed to be responsible for the membrane curvature that promotes budding because it packs densely into membranes. The membrane proteins S and E are also acquired during the budding process. The viroporin-like ion channel activity of E modifies cell secretory pathways to encourage virus release. E could improve the pH of the transport vesicles as one of its functions.

Exocytosis is the process by which membrane-bound vesicles containing virus particles are discharged from cells ⁴⁵.

How Variants are classified: To improve coordination between the CDC, National Institutes of Health (NIH), Food and Drug Administration (FDA), Biomedical Advanced Research and Development Authority (BARDA), and Department of Defence, the U.S. Department of Health and Human Services (HHS) established a SARS-CoV-2 Interagency Group (SIG) (DOD). This interagency team is concentrated on the quick characterization of novel variations and actively tracks their potential influence on crucial SARS-CoV-2 countermeasures, such as vaccinations, treatments, and diagnostics. The SIG meets frequently to assess the threat posed by SARS-CoV-2 variants present in the US and to offer suggestions about variant classification. A team of experts in the field evaluates the information that is currently available, including variant proportions at the national and regional levels and the potential or known effects of the constellation of mutations on the efficacy of medical interventions, the severity of the illness, and the capacity for contagion. Variants may be reclassified based on their characteristics and prevalence in the United States in light of the fact that SARS-CoV-2 is a living organism that is constantly evolving and our understanding of how variants affect public health (CDC.gov.2021). https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html ⁴⁶.

• Variants being monitored (VBM)
• Variant of interest (VOI)
• Variant of Concern (VOC)
• Variant of high consequence (VOHC)

TABLE 2: CLASSIFICATION OF COVID-19 VARIANTS

https://www.cdc.gov/coronavirus/2019-ncov/variants/variant-classifications.html ⁴⁶.

Covid-19 Vaccine: A COVID-19 vaccination is a shot meant to protect against the coronavirus illness 2019 (COVID-19), also known as the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2). The structure and operation of coronaviruses that cause diseases like Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) were well understood before the COVID-19 pandemic (MERS). This information sped up the creation of several vaccine platforms in early 2020 ⁴⁷. The SARS-CoV-2 vaccines initial goal was to avoid symptoms of the frequently serious sickness ⁴⁸. The genetic sequence data for SARS-CoV-2 was made available through GISAID in January-March 2020 and by March 2020, the global pharmaceutical sector had made a significant investment to combat COVID-19. The initial COVID-19 vaccinations were created and distributed to the general population in 2020 thanks to emergency authorizations and conditional approvals. With the Janssen COVID-19 vaccine being the lone exception, the majority of COVID-19 vaccinations were initially two-dose vaccines. However, it has been discovered that vaccine immunity wanes over time, necessitating booster doses of the vaccine to maintain protection against COVID-19. The genetic sequence data for SARS-CoV-2 was made available through GISAID in January 2020, and by March 2020, the global pharmaceutical sector had made a significant investment to combat COVID-19. The initial COVID-19 vaccinations were created and distributed to the general population in 2020 thanks to emergency authorizations and conditional approvals. With the Janssen COVID-19 vaccine being the lone exception, the majority of COVID-19 vaccinations were initially two-dose vaccines. However, it has been discovered that vaccination immunity wanes with time, necessitating booster doses of the vaccine in order to retain protection against COVID-19. The COVID-19 vaccines are largely recognized for helping to stop the disease spread as well as its severity and fatality rates ⁴⁹. Ten vaccines, including those produced by Pfizer-BioNTech, Oxford-AstraZeneca, Sinopharm BIBP, Moderna, Janssen, CoronaVac, Covaxin, Novavax, Convidecia, and Sanofi-GSK, have received approval for either emergency use or full use. Sputnik V, Sinopharm WIBP, Abdala, Zifivax, Corbevax, COVIran Barekat, and SCB-2019 are the other seven drugs that the WHO is currently evaluating. Out of the 40 vaccines, 16 have full or emergency approval in just one nation, 12 in ten or fewer nations, and 12 in more than ten. Be aware that in some countries, vaccinations may only be permitted for travel. They might not be accepted for use by the general public. The CoronaVac, Covishield, BBIBP-CorV, and Covaxin vaccines, for instance, are recognized for travel to Australia but are not included in Australia's national vaccination program. COVID-19 vaccines are authorized for emergency use or approved for full use ⁵⁰.

TABLE 3: LIST OF COVID-19 VACCINE AUTHORIZATIONS ⁵¹

Prevention: Information on the COVID-19 vaccination, COVID-19 workplace hazard controls, Non-pharmaceutical intervention, and pandemic prevention COVID-19 preparations, COVID-19 monitoring, and COVID-19 applications Pathogens can spread rapidly in the absence of pandemic containment measures such as social isolation, immunization, and face masks. This diagram demonstrates how early adoption of containment measures typically tends to protect larger segments of the population. Vaccination, staying at home, wearing a mask in public, avoiding crowded areas, keeping a distance from others, ventilating indoor spaces, controlling potential exposure durations, washing hands frequently and for at least 20 seconds, practicing good respiratory hygiene, and avoiding touching the eyes, nose, or mouth with unwashed hands are all preventive measures to lessen the likelihood of infection.

The CDC advises people with COVID-19 or those who think they may be infected to stay at home unless they need medical attention, call ahead before going to the doctor's office, wear a face mask when in a shared room or vehicle, cover coughs and sneezes with tissues, frequently wash their hands with soap and water, and avoid sharing personal household items. On December 2, 2020, the UK pharmaceutical authority MHRA (Medicines and Healthcare Products Regulatory Agency) gave the first COVID-19 vaccination regulatory approval. The US FDA and numerous other nations assessed it for emergency use authorization (EUA) status. In the beginning, the US National Institutes of Health guidelines did not suggest any medication for COVID-19 prophylaxis, either before or after exposure to the SARS-CoV-2 virus. One of the most important aspects of managing COVID-19 is attempting to lessen and delay the epidemic peak, sometimes known as "flattening the curve," in the absence of a vaccine, other preventative measures, or efficient treatments. This is accomplished by reducing the rate of infection to lower the possibility that health systems would become overburdened, allowing for better treatment of cases that are already active, and postponing the onset of new instances until cures or vaccines are developed ⁵².

Vaccine: The coronavirus disease 2019 (COVID19) is caused by the SARS-CoV2 virus, and a COVID19 vaccine is a vaccination designed to induce acquired immunity against this virus. Before the COVID-19 pandemic, a corpus of knowledge regarding the structure and operation of coronaviruses responsible for illnesses including Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) already existed. The creation of numerous vaccination platforms during the first half of 2020 was sped up by this information ⁴⁷. The main goal of SARS-CoV-2 vaccinations was to prevent symptomatic illness, which is frequently very serious. The genetic sequence data for SARS-CoV-2 was made available through GISAID in January 2020, and by March 2020, the global pharmaceutical sector had made a significant investment to combat COVID-19. The first COVID-19 vaccinations were created and distributed to the public in 2020 thanks to conditional permissions and emergency authorizations. However, it has been discovered that vaccine immunity wanes over time, necessitating booster doses of the vaccine to maintain protection against COVID-19 ⁴⁸.

Face Masks and Respiratory Hygiene: The WHO and the US CDC advise people to use non-medical face coverings in public places where there is a higher risk of transmission and when it is challenging to maintain social distance practices. This advice is supposed to supplement proven preventive measures like social seclusion and is intended to lessen the transmission of the illness by asymptomatic and presymptomatic patients. Face covers reduce the amount and dispersion of exhalatory droplets released during breathing, speaking, and coughing. A face mask without vents or holes can help reduce the risk of infection by filtering out virus-carrying particles from the air breathed in and exhaled. Nevertheless, if the mask has an exhalation valve, an infected (and possibly asymptomatic) wearer could pass the virus through the valve. To stop the spread of the virus, several nations and local governments promote or require that people cover their faces with cloth or face masks ⁵³.

FIG. 7: A SELECTION OF PROTECTIVE MASKS ⁵⁴

Hand-washing and Hygiene: It is necessary to thoroughly wash your hands when you cough or sneeze. Additionally, the WHO advises people to often wash their hands with soap and water for at least 20 seconds, especially after using the restroom, before eating, after blowing their noses, and otherwise when their hands are obviously dirty. The CDC advises using an alcohol-based hand sanitizer with at least 60% alcohol when soap and water are not readily available. The WHO offers two formulations for local manufacturing in regions where commercial hand sanitizers are not easily accessible. Ethanol or isopropanol are the sources of the antibacterial action in these compositions. Hydrogen peroxide helps remove bacterial spores from alcohol but is "not an active agent for hand antisepsis." Added as a humectant is glycerol ⁵⁵.

Social Distancing: Physical and social barriers are used in infection control to prevent intimate contact between people, which is meant to inhibit the spread of disease. Quarantines, travel restrictions, and the closure of workplaces, schools, stadiums, theatres, or retail malls are a few examples of methods. Staying at home, restricting travel, avoiding crowded places, utilizing no-contact greetings, and physically separating themselves from others are all examples of social distancing techniques that people can use. Many governments are requiring or advising social seclusion in areas where the pandemic is occurring ⁵⁶.

Self-isolation: For those with a diagnosis of COVID-19 or who believe they may be infected, self-isolation at home has been advised. Health organizations have published comprehensive guidelines for appropriate self-isolation. Many governments have required or advised population-wide self-quarantine.

Those who are members of high-risk categories have received the strictest self-quarantine guidelines. It has been suggested that persons who may have come into contact with someone who has COVID-19 and those who have recently visited a place where the disease is being widely transmitted self-quarantine for 14 days starting from the time of their last probable exposure ⁵⁷.

International Travel-related Control Measures: According to a 2021 Cochrane quick assessment, cross-border travel restrictions and other international travel-related control measures may assist in slowing the spread of COVID-19. Additionally, border screening procedures based on symptoms or exposure may fail to detect many positive cases.

Test-based border screening procedures may be more successful, but if they are just used once at the border and are not followed up on, they risk missing many positive instances. The study found that a minimum 10-day quarantine might help stop the spread of COVID-19 and might be even more effective if used in conjunction with another management approach like border screening ⁵⁸.

Death Rate Depends on Age, Health, and Sexes: According to Tedros Adhanom Ghebreyesus, director-general of the World Health Organization, around 3.4% of recorded COVID-19 instances have resulted in fatalities worldwide. According to Matt Hancock, the health secretary for the UK government, the fatality rate is "2% or, possibly, lower." However, it varies depending on a number of variables, including general health, age, sex, and the healthcare system in your area. Women were the first to be greatly affected by the coronavirus. Nevertheless, from country to country, the figures vary slightly. It doesn't always correspond to biological differences. Scientists are still unsure for sure, but it's possible that men engage in unhealthy behaviors like drinking and smoking more frequently than women on average ⁵⁵.

FIG. 8: A GRAPH SHOWED ON DEATH RATE DEPENDS ON AGE, HEALTH, AND GENDERS ⁵⁵

Countries or Territories with Reported Cases and Deaths: 229 nations and territories are currently impacted by the COVID-19 coronavirus. The day is restarted at 00:00 GMT. The United Nations Geoscheme is the foundation for the list of nations and their regional categorization. Under "Latest News," sources are listed. Learn more about the COVID-19 statistics from World meter [https://www.worldometers.info/coronavirus/ ] ⁵⁹.

TABLE 4: THE NATIONS OR TERRITORIES WHERE CASES AND DEATHS HAVE BEEN REPORTED

Highlighted in green= all cases have recovered from the infection. Highlighted in grey = all cases have had an outcome (there are no active cases).

CONCLUSION: People all across the world are currently being affected by the COVID-19 pandemic. Current management focuses on stopping the spread of the virus and giving sick patients supportive care without fundamental therapeutic procedures.

Future COVID-19 vaccines should take into consideration factors such as the creation of heat-stable vaccinations that are simple to give in tropical environments with limited resources. Regardless of political differences, nations may come together and collaborate to quickly and effectively implement the COVID-19 vaccination internationally.

ACKNOWLEDGEMENT: The Corresponding author would like to thanks Neda Fatima, Hira Moid, Anil Kumar for encouraging and supporting the manuscript's preparation.

CONFLICT OF INTEREST: The authors have no conflict of interest to declare.

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    Nisha N, Fatima N, Moid H and Kumar A: A review of covid-19 identification, classification, therapy, prevention and vaccination. Int J Pharm Sci & Res 2024; 15(2): 353-71. doi: 10.13040/IJPSR.0975-8232.15(2).353-71.

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