COVID-19: A Multidisciplinary Review

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that is responsible for the 2019-2020 pandemic. In this comprehensive review, we discuss the current published literature surrounding the SARS-CoV-2 virus. We examine the fundamental concepts including the origin, virology, pathogenesis, clinical manifestations, diagnosis, laboratory, radiology, and histopathologic findings, complications, and treatment. Given that much of the information has been extrapolated from what we know about other coronaviruses including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), we identify and provide insight into controversies and research gaps for the current pandemic to assist with future research ideas. Finally, we discuss the global response to the coronavirus disease-2019 (COVID-19) pandemic and provide thoughts regarding lessons for future pandemics.

Keywords: COVID-19; SARS-CoV-2; coronavirus; global health; pandemic; respiratory infection.

Figure 1

COVID-19: timeline to pandemic. The sequence of events from the outbreak in Wuhan, China to the declaration of the COVID-19 pandemic. BALF, bronchoalveolar lavage fluid.

Figure 2

SARS-CoV-2 structure. Viral structure with its protein components and viral RNA (vRNA).

Figure 3

COVID-19 pathogenesis. 1. A. SARS-CoV-2 enters the epithelial cell either via endocytosis or by membrane fusion through binding to ACE2 receptor and releasing its RNA into the cytoplasm. B. Viral RNA uses the cell's machinery to translate its viral non-structural and structural proteins and replicate its RNA. C. Viral structural proteins S, E, and M assemble in the rough endoplasmic reticulum (RER). D. Viral structures and nucleocapsid subsequently assemble in the endoplasmic reticulum golgi intermediate (ERGIC). E. New virion packed in golgi vesicles fuse with the plasma membrane and get released via exocytosis. 2. SARS-CoV-2 infection induces inflammatory factors that lead to activation of macrophages and dendritic cells. 3. Antigen presentation of SARS-CoV-2 via major histocompatibility complexes I and II (MHC I and II) stimulates humoral and cellular immunity resulting in cytokine and antibody production. 4. In severe COVID-19 cases, the virus reaches the lower respiratory tract and infects type II pneumocytes leading to apoptosis and loss of surfactant. The influx of macrophages and neutrophils induces a cytokine storm. Leaky capillaries lead to alveolar edema. Hyaline membrane is formed. All of these pathological changes result in alveolar damage and collapse, impairing gas exchange.

Figure 4

The association between SARS-CoV-2 and the Renin-Angiotensin-Aldosterone System (RAAS). SARS-CoV-2 binds to ACE2 receptor and enters into the cell. It has been hypothesized that this process leads to down-regulation of surface ACE2, resulting in unopposed angiotensin II buildup and activity, leading to a pro-inflammatory cascade. Alternative hypotheses are further described in the text. The uncertainties regarding the role of ACE-Is and ARBs in COVID-19 are also discussed. Ang, angiotensin; ACE, angiotensin-converting enzyme; AT1, angiotensin II type 1 receptor.

Figure 5

COVID-19 lung autopsy specimen. This figure is original and based on data from (46). It demonstrates COVID-19 pathology as seen in the lungs of an autopsied case (case 1, Barton et al.). (A) Diffuse alveolar damage. The arrow points to a hyaline membrane. (B) Interstitial lymphocytic inflammatory infiltrate. The arrow indicates lymphocytes within an alveolar septum. Hematoxylin-eosin stain, 200×, both images.

Figure 6

Small blood vessels in various organs in COVID-19. This figure is original and based on data from (46). No thrombi are seen in the small blood vessels of the (A) Lung. (B) Heart. (C) Kidney (glomerulus). (D) Liver (portal tract) (autopsy case 1, Barton et al.).

Figure 7

COVID-19 positive patient chest computed tomography (CT). This figure is original and illustrates the findings from (76). It demonstrates bilateral, predominately peripheral, patchy ground-glass opacities consistent with multi-lobar pneumonia.

Figure 8

COVID-19 positive patient chest x-ray (CXR). This figure is original and illustrates the findings from (78). It demonstrates bilateral predominately mid to lower lung field airspace opacities.