Understanding COVID-19: From Origin to Potential Therapeutics

Abstract

Currently, a global pandemic era of public health concerns is going on with the Coronavirus Disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The first case of COVID-19 was reported from Wuhan's Huanan seafood market in China late December 2019. Bats, pangolins, and snakes have been nominated as salient carriers of the virus. Thanks to its high pathogenicity, it can cause severe respiratory infections. Fever, dry cough, sore throat, pneumonia, septic shock, and ground-glass opacities are the foremost clinical manifestations of COVID-19. Immunocompromised patients are at high risk for COVID-19 infection and may lead to death. Scientist and government agencies around the globe are putting forward their best efforts and resources for the effective treatment of human coronavirus infections; however, neither vaccines nor antiviral drugs are available for the treatment of human coronaviruses (HCoV) infections such as SARS (severe acute respiratory syndrome), MERS (Middle Eastern respiratory syndrome), and COVID-19. Since the outbreak, a plethora of research and review articles have been published. Moreover, the mass media has bombarded the public with conflicting opinions about the pandemic. There is a dire need for accurate and reliable information concerning this pandemic. In this review, we have compiled the up to date information about the origins, evolution, epidemiology, and pathogenesis of this disease. Moreover, very few reports have addressed the clinical features and current status of treatment for COVID-19; we have adequately addressed these topics in detail in this review. Finally, a detailed account of clinical trials of vaccines and other therapeutics currently in progress has been delineated.

Keywords: COVID-19; RT-PCR; SARS-CoV-2; clinical features; cytokine storm; dexamethasone; epidemiology; life cycle; pathogenesis; remdesivir; therapeutics; vaccines.

Figure 1

The life cycle of a coronavirus, modified, and used from Zhang et al. [27] with an open-access journal license. Upon entry to the host lungs, the CoV attaches to angiotensin-converting enzyme (ACE-2) receptors and releases its nuclear content into the cytoplasm. Translation of the RNA makes replicase complex, which results in the formation of transcripts of several proteins (named in pink box). Translation of these transcripts makes spike (S), envelope (E), membrane (M), nucleocapsid (N), and other accessory proteins. Assembly of these proteins produces a new virion that is matured and is released out of the cell to infect other cells.

Figure 2

Inflammatory responses during severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. SARS-CoV-2 attaches to the ACE2 receptor, and the spike protein is cleaved by the type II transmembrane serine protease (TMPRSS2), resulting in viral replication. Mature viruses are released from the cell by exocytosis. In the dysfunctional immune response, cells may undergo pyroptosis and release adenosine triphosphate (ATP), nucleic acids, and ASC oligomer. These impaired-associated molecular forms can be detected by the neighboring epithelial cells and other alveolar macrophages. In response, the pro-inflammatory cytokines are released along with chemokines, including IL-6, IP-10, macrophage inflammatory protein 1α (MIP1β), MCP1, and MIP1α. These released proteins draw the monocytes, T cells, and lymphocytes to the inflammatory site, causing exaggerated inflammation at the site of action. This exaggerated response damages the lung’s infrastructure. This cytokine storm can move to other organs and may damages the other organs as well.

Figure 3

Atypical CT imaging of a 56-year-old female presented with a history of 3 days of persistent fever. Laboratory findings: reduced total protein level (54.0 g/L), reduced albumin value (35.5 g/L), low value of globulin (18.5 g/L), white blood cells (WBCs) (4.87 × 10⁹/L), lymphocytes (0.49 × 10⁹/ L), and decreased level of eosinophil (0 × 10⁹/L). Imaging inspection: (A) A lateral section of the center of right lung lobe covered GGO. (B) Patchy GGO in the upper part of the right lung with sporadic consolidated lesions. (C) GGO in both lungs with sporadic consolidation lesions. (D) Uneven GGO in the middle and dorsal section of the right lung. Adopted from Kui et al. through open-access license [69].