In Wuhan, Hubei, China, on December 31, 2019, a number of acute unusual respiratory illnesses manifested. This quickly spread outside of Wuhan. It rapidly became apparent that a brand-new coronavirus (beta-coronavirus) from the Coronaviridae family was causing the problem. Due to its strong homogeneity to SARS-CoV, which caused acute respiratory distress syndrome (ARDS) and a respiratory pandemic with a high fatality rate in 2002–2003, the novel coronavirus was given the name severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, 2019-nCoV). 1,2 Using zoonotic transmission linked to seafood in a market in Wuhan, China, SARS-CoV-2 spread across the community. Later, it was shown that SARS-CoV-2 transfer from person to person is a major factor in the disease's global spread and the development of a pandemic crisis.3

After being a public health emergency and wide community spread throughout 200 countries WHO declared COVID-19 pandemic on March 11, 2020.4,5 A lot of people have been impacted by COVID-19, which has been documented in about 200 nations and territories worldwide. According to the Centre for Systems Science and Engineering (CSSE) at John Hopkins University, there have been over 1,400,000 cases reported globally as of April 7th, 2020, with approximately 536 893 documented deaths.6 Although other organ systems are also affected, the respiratory system is the one that is initially impacted by novel coronavirus. In the first case series from Wuhan, China, symptoms associated with lower respiratory tract infections such as fever, dry cough, and dyspnea as well as headache, generalised weakness, and vomiting were noted.6,7 The COVID-19 mortality rate is higher in elderly people with comorbidities such hypertension, diabetes mellitus, cardiac risks, and acute or severe renal and hepatic disorders, according to epidemiological studies. When infected with a virus, patients who are immunosuppressed, have cancer or are pregnant are also more likely to experience severe illness. Since there isn't a known specific treatment for SARS-CoV-2, the majority of medical attention provided nowadays is supportive.2,8 When compared to earlier respiratory pandemics of SARS-CoV-1 in 2003 and the Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 2012, this virus is more dangerous to humans and spreads quickly throughout communities than other endemic viruses.1  Coronavirus has large (around 30 kb) single-stranded, positive-sense RNA genomes and shares about 80% of its nucleotides with other coronaviruses. RaTG13-2013, a virus found in bats, is very similar to SARS-CoV-2 (shares 90% of its nucleotide structure).2,9

As a result of the ongoing COVID-19 epidemic, various human-to-human transmission routes have been reported. The most prominent and highly implicated route of transmission documented during the epidemic is droplet transmission (>5 ?m). (Figure 1) Human-to-human transmission has also been linked to direct contact between an infected person and a naïve person, particularly in homes where family members interact closely. Although it occurs less frequently than droplet or contact-driven transmission, the contagiousness of SARS-CoV-2 after disposition on fomites (e.g., door handles) is still being investigated. 39

Although they have not yet been noted in the present crises, both airborne and fecal–oral human-to-human transmission events have been recorded in the preceding SARS-CoV epidemic. Solid arrows show confirmed viral transmission from one infected individual to anotherviral transmission from one infected individual to another is shown by solid arrows; a decreasing gradient in arrow width indicates the relative contributions of each transmission pathway. The probability of transmission types that are not yet confirmed is indicated by dashed lines. When an RNA or infectious virus is found, it is indicated by the SARS-CoV-2 symbol in the "infected patient" field. 39

PATHOLOGY

Coronaviruses are positive-sense, 30 kb enclosed viruses with a single-stranded RNA genome. They affect many different host species. 1 Based on their genetic structure, they are typically divided into four genera: ?, ?, ?, and ?.  mammals are infected by only ? and ? coronaviruses.10 Human coronaviruses, including 229E and NL63, are known to be the source of the common cold and croup. MERS-CoV is the coronavirus responsible for the Middle East respiratory syndrome, but SARS-CoV, MERS-CoV, and SARS-CoV-2 are all coronaviruses. The five stages of the virus's life cycle within the host are attachment, penetration, biosynthesis, maturation, and release. 4 Pathogens, such as viruses, are those that adhere to host receptors and penetrate host cells by endocytosis or membrane fusion. (Figure 2)

Structure of virus:  

The four principal structural protein-coding genes present in coronaviruses are spike protein (S), envelope protein (E), membrane protein (M), and nucleocapsid protein (N). 11 Angiotensin-converting enzyme (ACE2) serves as the SARS-spike CoV-2 protein's cell surface receptor, controlling the tropism of the virus.2 The most important component for viral attachment and host penetration, the S protein, is visible and protrudes from the viral surface. Two functional subunits (S1 and S2) make up this protein, with S1 being in charge of attaching to the host cell receptor and S2 being in charge of fusing the membranes of the host and viral cells. 1 While the viral M protein facilitates integration into the cellular endoplasmic reticulum, the viral N protein binds the new genomic RNA. 11 These recently produced Nucleocapsids are then encapsulated in the ER membrane and transported to the lumen, where they are then transported to the cell membrane via Golgi vesicles and, finally, to the extracellular environment by exocytosis.4

DIAGNOSIS

In patients with clinical evidence of COVID-19 infection, laboratory tests may reveal I lymphocytopenia, (ii) thrombocytopenia, (iii) elevated liver transaminases, (iv) elevated C-reactive protein and erythrocyte sedimentation rate, (v) elevated serum lactate dehydrogenase, and (vi) decreased or normal serum albumin.1,2

1. Viral testing

This test, known as RT-qPCR, is used to qualitatively identify the SARS-CoV-2 nucleic acid. Swabs are typically obtained from lower respiratory tract aspirates or washes, nasal, nasopharyngeal, oropharyngeal, sputum, or sputum. Positive test results show that SARS-CoV-2 RNA is present, which supports the diagnosis when combined with the clinical presentation. Negative test findings should be interpreted in the context of the clinical picture and available epidemiological data, as they do not rule out SARS-CoV-2 infection. 1,2

2. Serology

The test cannot be used to diagnose an infection that is currently present, but it can evaluate previous exposure to the virus. There could be cross-reactivity with different human coronaviruses. When the viral test is unavailable, the serology test is especially helpful (i). Making decisions can be guided by the serology test in conjunction with the clinical picture; (ii) Patients who present with late complications of the disease require prompt medical attention from physicians due to the longer turnaround time for viral testing results; (iii) In certain patients, viral shedding is reduced, leading to false negative results from RT-qPCR. IgM and IgG antibodies against SARS-CoV-2 can be found in serum, plasma, and whole blood using the serology test. 1,2

3. Rapid antigen testing

This assay uses a monoclonal antibody to detect the nucleocapsid (N) protein of SARS-CoV-2. Infected cells express this protein abnormally. SARS-CoV-2 can be detected utilising enzyme-linked immunosorbent test (ELISA) and monoclonal antibodies that are particularly directed towards N protein. The test's stated specificity is 98.5%, and its sensitivity is 84.1%. There were no known cross-reactions between the assay's human and animal coronaviruses. As of yet, there are no reports of using this test on SARS-CoV-2. 1,2

4. Ultrasonography

Complete body point of care Ultrasonography has been applied to COVID-19 patients. When treating patients with cardiorespiratory failure, ultrasound is seen to be a crucial tool in the intensive care unit (ICU) and the wards. As of right now, using it for multisystem and whole-body sonography for thoracic, cardiac, abdominal, and deep vein thrombosis is advised. 1,2

5. Computed tomography (CT) scan of the chest

Prior research conducted during the Chinese outbreak revealed that pneumonia patients with and without SARS-CoV-2 could be distinguished using CT chest imaging in addition to clinical presentation. The authors suggest that clinical features and radiological imaging can make good COVID-19 diagnostic tools. A patient's age, the existence of comorbidities, a high viral load, an elevated neutrophil lymphocyte ratio (NLR), changes in the CT chest and the extent of the lesion, and CT chest changes are all potential indicators of severe disease. 1,2

Extrapulmonary changes in COVID-19

Vaccines for COVID-19

There is an international effort to develop a SARS-CoV-2 vaccine, and as of the end of August 2020, 30 vaccines were undergoing clinical trials, with more than 200 others in various stages of development. 12 A number of platforms are being taken into consideration for the development of COVID-19 vaccines. (Table 1) Among these are RNA, DNA

Antiviral treatment for covi

The majority of COVID-19 medications are authorized antiviral agents or antibodies that are used to treat diseases other than COVID-19.14

Theoretically, in the early stages of COVID-19, treatment with effective antiviral agents could provide greater benefits. In addition to antiviral therapy, anti-inflammatory agents may aid crucial COVID-19 patients with cytokine release syndrome. (Table 2)15

Other than antiviral agents for the treatment of COVID-19 2,14,

Novel Anti-Viral agents used in COVID-19:

Molnupiravir:

Merck Sharp & Dohme and Ridgeback are collaborating to create the experimental pharmaceutical drug molnupiravir (Table 4), also known as MK-4482, EIDD-2801, and MOV; Lagevrio is a possible brand name for the drug.32

The ribonucleoside analogue prodrug Molnupiravir (EIDD-2801) is ingested and is available as a tablet. In addition to coronaviruses like SARS-CoV-2, MERS-CoV, and SARS-CoV, molnupiravir exhibits broad-spectrum antiviral efficacy against influenza. Research on COVID-19, as well as seasonal and pandemic influenza, has the potential to use molnupiravir.33

In clinical trials, molnupiravir is offered as a 200 mg hard capsule for oral dosages. The suggested dosage is 800 mg of molnupiravir (given as four 200 mg capsules) taken orally every 12 hours with or without food for five days.34

The antiviral ribonucleoside analogue N-hydroxycytidine (NHC) has a 5'-isobutyrate prodrug called molnupiravir. The pharmacologically active ribonucleoside triphosphate (NHC-TP), which operates through a viral error catastrophe mechanism, is created when the prodrug molnupiravir is metabolised to NHC. NHC-TP is incorporated into viral RNA by the viral polymerase, which leads to an accumulation of errors in the viral genome and replication inhibition.33

Physicochemical properties:33,34

Nirmatrelvir (Table 5), also known as 3CLpro or NSP5 protease, is a peptidomimetic inhibitor of the SARS-CoV-2 3C-like protease main protease (Mpro).37 The Pfizer-developed SARS-CoV-2 3CL protease inhibitor prevents viral replication by inhibiting the digestion of polyprotein precursors. Lufotrelvir, an earlier clinical candidate, was modified to become nirmatrelvir.36 A SARS-CoV-2 major protease inhibitor with wide coronavirus antiviral effectiveness, strong off-target selectivity, and consequently fewer adverse medication reactions is nirmatrelvir (or PF-07321332)/ritonavir, produced by Pfizer, Inc.37

CONCLUSION