The hallmarks of COVID-19 disease

Abstract

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel coronavirus that has caused a worldwide pandemic of the human respiratory illness COVID-19, resulting in a severe threat to public health and safety. Analysis of the genetic tree suggests that SARS-CoV-2 belongs to the same Betacoronavirus group as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Although the route for viral transmission remains a mystery, SARS-CoV-2 may have originated in an animal reservoir, likely that of bat. The clinical features of COVID-19, such as fever, cough, shortness of breath, and fatigue, are similar to those of many acute respiratory infections. There is currently no specific treatment for COVID-19, but antiviral therapy combined with supportive care is the main strategy. Here, we summarize recent progress in understanding the epidemiological, virological, and clinical characteristics of COVID-19 and discuss potential targets with existing drugs for the treatment of this emerging zoonotic disease.

Fig 1. Main events of Wuhan coronavirus outbreak.

ICTV, International Committee on Taxonomy of Viruses; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; WHO, World Health Organization.

Fig 2. Hosts and consequences of human CoV infection.

Different human CoVs have different natural and intermediate hosts. Among them, HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 cause mild infection, whereas SARS-CoV, MERS-CoV, and SARS-CoV-2 lead to mild or lethal respiratory diseases. 9-0-Ac-Sia, 9-O-acetylated sialic acids; ACE2, angiotensin I-converting enzyme 2; ANPEP (also known as CD13), alanyl aminopeptidase, membrane; CoV, coronavirus; DPP4 (also known as CD26), dipeptidyl peptidase 4; HCoV, human coronavirus; MERS-CoV, Middle East respiratory syndrome coronavirus; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2.

Fig 3. Schematic representation of the taxonomy of Coronaviridae.

BuCoV-HKU11, bulbul coronavirus HKU11; HCoV, human coronavirus; MERS-CoV, Middle East respiratory syndrome coronavirus; SARS-CoV, severe acute respiratory syndrome coronavirus; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2.

Fig 4. A model of the life cycle and immune response to SARS-CoV-2 in host cells.

ACE2 is the host cell receptor responsible for mediating infection by SARS-CoV-2. After endocytosis and subsequent uncoating, the components of SARS-CoV-2 can be reused to produce new virus by host cells. Finally, the virus is released from the host cell by exocytosis. On the other hand, SARS-CoV-2–mediated host DNA damage or the components of SARS-CoV-2 can bind various cytosolic PRRs, leading to the activation of TMEM173- or GSDMD-dependent pyroptosis, which causes cytokine and DAMP release and subsequent inflammation, immunity, and coagulation dysfunction through impairment or activation of various immune cells, such as T cells, B cells, dendritic cells, NK cells, macrophages, and neutrophils. This process is involved in the activation of transcription factors, such as IRF3 and NF-κB. If not recognized early and managed promptly, it can lead to septic shock, multiple organ failure, and death. Ab, monoclonal antibody; ACE2, angiotensin I-converting enzyme 2; CASP1, caspase 1; CASP11, caspase 11; CQ, chloroquine; DAMP, damage-associated molecular pattern; DC, dendritic cell; GSDMD, gasdermin D; HCQ, hydroxychloroquine; HMGB1, high-mobility group Box 1; IRF3, interferon regulatory factor 3; NF-κB, nuclear factor κB; NK, natural killer; PRR, pattern-recognition receptor; SARS-CoV-2, severe acute respiratory syndrome coronavirus-2; TMEM173, transmembrane protein 173; TMPRSS2, transmembrane protease serine 2.