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COVID-19: A Pandemic - Introduction

Pratik Kulkarni1, Tejas Barot1, Piyush Rao1, Aayush Dey1, and Deepak Rawtani2

1 School of Doctoral Studies & Research (SDSR), National Forensic Sciences University (Ministry of Home affairs, GOI), Gandhinagar, Gujarat, India

2 School of Pharmacy, National Forensic Sciences University (Ministry of Home affairs, GOI), Gandhinagar, Gujarat, India

1.1 Introduction: Sources and Chemical Activities of COVID-19

Coronavirus or COVID-19 is an infectious disease caused by a novel virus known as extreme coronavirus-2 respiratory syndrome (SARS-CoV-2). It began to spread as a disease from Wuhan, the capital of the province of Hubei in China, in December 2019. It has since spread worldwide, contributing to an ongoing pandemic, as announced by the WHO on 11 March 2020 (Hui et al. 2020; Hui and Zumla 2019; Tang et al. 2020b). With more than 9 months under the pandemic, more than 70 million people have been tested positive for infection and more than a million deaths and counting worldwide. Its primary source was identified in the respiratory tract of patients in Wuhan undergoing treatment for pneumonia, which was then identified as the new SARS-CoV-2 virus.

The original source of the virus is still unknown, but the first cases were related to the Huanan Seafood Market in Wuhan. There are also some wild animals known to be sold on the market, including birds, marmots, bats, and snakes. It was shown that market samples were positive for the novel virus, but the animal was not specified (Astuti 2020; Guo et al. 2020; Tian et al. 2020). However, recent reports have suggested that bats could be the potential host of the virus as they shared96 % homology of the entire genome-wide sequence with the bat CoV. From the genetic analysis, a region of RNA-dependent RNA polymerase (RdRP) gene in SARS-CoV-2 was confirmed to be similar to a region of RdRP found in bat coronavirus RaTG13 with an astounding 96% homology of the genome sequence. Of more than 100 strains sequenced till the end of March, a 99.9% sequence match was observed but since then several changes in the genome have been discovered, which show a high probability of sequence diversity in the virus. Pangolin CoV genomes have also been found to have an 85.5-92.4 % homology with SARS-CoV-2, indicating that SARS-CoV-2 could be a potential intermediate host. How the virus transmits from either bats or pangolins needs to be studied more for a better confirmation (Harapan et al. 2020; Shereen et al. 2020; Udugama et al. 2020; ul Qamar et al. 2020).

1.1.1 Sources and Transmission

Currently, the source of transmission is known to be from human to human through respiratory droplets. Yet, not the only probable source of transmission is the respiratory tract. As a source of transmission, close contact has also been confirmed (Figure 1.1). For example, the virus can be transmitted by direct or indirect contact with the mucous membranes of the eye, mouth, or nose (Hui and Zumla 2019; Hui et al. 2020; Tang et al. 2020b). In a closed environment with relatively high aerosol concentrations, the possibility of aerosol transmission also exists (Astuti 2020). Some gastrointestinal symptoms have also been reported including diarrhea, nausea, and vomiting. All populations are vulnerable to the virus. Mostly elderlies and people with a weak immune function or underlying diseases are likely to become severely affected by the virus. Additionally, pregnant women and new-born babies infected with the virus can develop severe pneumonia. This group of patients should therefore be considered to be of primary importance in preventing and managing SARS-CoV-2 attacks (Astuti 2020; ul Qamar et al. 2020).

Figure 1.1 A schematic diagram showing SARS-CoV-2 transmission through different routes.

1.1.2 Structure of SARS-CoV-2

The virus is recognized as a non-segmented, enveloped, positive-sense RNA virus that is part of the subfamily of sarbecovirus, orthocoronavirinae, widely distributed in humans and other mammals. SARS-CoV-2 is about 60-140 nm in diameter and contains single-stranded RNA with 30,000 nucleotides in length (Wu et al. 2020). It is characterized by a distinct crown-like spikes on its outer surface, and its genome has 27 encoded proteins which also includes RdRP and 4 structural proteins with different functions namely Spike surface glycoprotein (S), which is involved in the coding for proteins that form receptor-binding spikes that help the virus to infect cells by binding to the receptors via embrane fusion (Sexton et al. 2016; Tang et al. 2020a; Wrapp et al. 2020). This binding also determines its host tropism and transmission capabilities. The other three proteins - Nucleocapsid protein (N), Small envelope protein (E), and Matrix protein (M) - are more conserved than the S protein and are essential for proper virus functioning. These proteins are involved in the encapsulation of RNA and/or proteins into protein assemblies, envelope formation, budding, and pathogenesis (Bauch and Orabyet al. 2013; Lim et al. 2016; Neuman et al. 2011; Schoeman and Fielding 2019).

SARS-CoV-2 is considered to have a long transmission period as its mean incubation time is estimated within three to seven days. It has also been reported that asymptomatic patients of the virus could be effective carriers during their incubation period (Udugama et al. 2020). This property is different from other SARS-CoV as most of those cases are transmitted via agents known as "superspreaders" and those who cannot infect others during their incubation period. These data thus support the current WHO guidelines of a 14-day quarantine period for active monitoring (Udugama et al. 2020; Yi et al. 2020).

1.1.3 Common Symptoms, Immune Reaction to the Virus, and Mechanism of Entry

Fatigue, fever, dry cough, dyspnea, and myalgia are key manifestations of the disease. Nasal congestion, sore throat, runny nose, headache, vomiting, and diarrhea are some less common symptoms (Figure 1.2). Patients termed under severe category often have dyspnea and/or hypoxia after a week of onset which is followed by septic shock, acute respiratory distress syndrome (ARDS), metabolic acidosis which is difficult to correct, and coagulation dysfunction that develops rapidly. Patients with mild fatigue, low fever, and absence of pneumonia can be considered asymptomatic but can still spread the virus between humans (Udugama et al. 2020; Zhou et al. 2020).

Figure 1.2 Clinical manifestations of infection with SARS-CoV-2 in humans.

Invasion of the virus into the host cell triggers an immune response which the innate immune system encounters through antigen presenting cells (APC), e.g. macrophages, dendritic cells (Chen et al. 2020; Guo et al. 2020; Huang et al. 2020). This APCs have specific receptors known as Pattern Recognition Receptors (PRR) located in several regions in the host cells like plasma and endosomal membranes, lysosomes, cytosol, and endocytolysosomes. Now, recognition of pathogen-associated molecular patterns (PAMP) comprising viral structural components including nucleic acid, carbohydrate moieties, glycoproteins induces cascade signaling to produce immune cell effectors which trigger a different biological response following protein activation. For instance, Toll-like receptor 4 (TLR-4) might induce the protein spikes of CoV to produce proinflammatory cytokines like IFN-a, IFN-?, IL-1ß, IL-6, TNF-a, TGFß and chemokines like CCL2,3,5, CXCL8,9,10. Their excessive release from the cells of the immune effector leads to hyperinflammation, resulting in ARDS eventually (Chen et al. 2010, 2020; Cheung et al. 2005; Huang et al. 2020; Li et al. 2020a, 2020c; Rabi et al. 2020).

Various studies have shown that SARS-CoV-2 host cell entry is regulated by its interaction with the angiotensin-converting enzyme 2 (ACE-2) (Zhou et al. 2020). A critical finding stated that in comparison to SARS-CoV, SARS-CoV-2 spikes bind to the ACE-2 enzyme with 10-20 times higher affinity, thereby making it easier to spread among the humans. Therefore, upon entry into the respiratory epithelial cells, the virus replicates quickly, along with triggering a strong immune response characterized by cytokine storm syndromes known as hypercytokinaemia. This group of disorders is characterized by an uncontrollable increase in cytokine production, which leads to ARDS and ultimately leading to multiple organ failure. Studies have revealed that many patients succumbed to multiple organ failure indicating a substantial decrease in T-cell population, whereas surviving T-cell population being functionally exhausted, indicated decreased immunity in the patients with secondary infections, worsening the respiratory failure even further (Li et al. 2020b).

1.1.3.1 Immuno-evasion of Coronaviruses

Viruses including the novel SARS-CoV-2 have several...