Human coronaviruses: The emergence of SARS-CoV-2 and management of COVID-19

Abstract

To date, a total of seven human coronaviruses (HCoVs) have been identified, all of which are important respiratory pathogens. Recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has led to a global pandemic causing millions of infections and deaths. Here, we summarize the discovery and fundamental virology of HCoVs, discuss their zoonotic transmission and highlight the weak species barrier of SARS-CoV-2. We also discuss the possible origins of SARS-CoV-2 variants of concern identified to date and discuss the experimental challenges in characterizing mutations of interest and propose methods to circumvent them. As the COVID-19 treatment and prevention landscape rapidly evolves, we summarize current therapeutics and vaccines, and their implications on SARS-CoV-2 variants. Finally, we explore how interspecies transmission of SARS-CoV-2 may drive the emergence of novel strains, how disease severity may evolve and how COVID-19 will likely continue to burden healthcare systems globally.

Keywords: COVID-19; Cross-species transmission; Human coronaviruses; Long COVID; SARS-CoV-2; Vaccines; Variants of concern.

Fig. 1

Timeline of HCoV discoveries. Blue represents the discovery of endemic HCoVs that generally cause the common cold. Green represents the discovery of highly pathogenic HCoVs.

Fig. 2

Schematic of HCoV viral particle and genome. (A) HCoV virions contain membrane and envelope proteins embedded into the lipid bilayer surrounding the viral particle. S proteins protrude from the surface of the viral particle. The +ssRNA genome is encapsulated by nucleocapsid proteins. (B) Schematic of the SARS-CoV-2 genome. Viral NSPs are predominantly involved in viral replication and are encoded by ORF1a and ORF1b. The remaining ORFs encode accessory and structural proteins, including the spike, envelope, membrane and nucleocapsid proteins.

Fig. 3

Zoonosis of HCoVs and interspecies transmission of SARS-CoV-2. (A) Schematic of zoonotic transmission of HCoVs from their respective reservoirs to their immediate host and subsequently to the human population. Green represents confirmed intermediate hosts and orange represents suspected intermediate hosts. Question marks represent unknown intermediate hosts. (B) Schematic of interspecies transmission of SARS-CoV-2 reported to date. Larger arrows represent large outbreaks and smaller arrows represent few documented cases.

Fig. 4

Timeline of earliest reports of SARS-CoV-2 VOCs reported to date.