SARS-CoV-2 variants: Impact on biological and clinical outcome

Abstract

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that was first identified in December 2019, in Wuhan, China was found to be the etiological agent for a novel respiratory infection that led to a Coronavirus Induced Disease named COVID-19. The disease spread to pandemic magnitudes within a few weeks and since then we have been dealing with several waves across the world, due to the emergence of variants and novel mutations in this RNA virus. A direct outcome of these variants apart from the spike of cases is the diverse disease presentation and difficulty in employing effective diagnostic tools apart from confusing disease outcomes. Transmissibility rates of the variants, host response, and virus evolution are some of the features found to impact COVID-19 disease management. In this review, we will discuss the emerging variants of SARS-CoV-2, notable mutations in the viral genome, the possible impact of these mutations on detection, disease presentation, and management as well as the recent findings in the mechanisms that underlie virus-host interaction. Our aim is to invigorate a scientific debate on how pathogenic potential of the new pandemic viral strains contributes toward development in the field of virology in general and COVID-19 disease in particular.

Keywords: COVID-19; SARS-CoV-2; coronavirus; diagnostics; host response; immune escape; variants; virus evolution.

Figure 1

Chronology of the emergence of SARS-CoV-2 variants during the pandemic. The month and date of the main events of the COVID-19 pandemic are presented year-wise and each year is shown with a different color. Appearance of a new variant and related information are highlighted with red color. A pictorial representation of each event has been added in the circle of respective date and month.

Figure 2

Structure of SARS-CoV-2 virus (A) structure of SARS-CoV-2 virion showing the structural proteins, Spike (S), Membrane (M), and Envelope (E) embedded in the host-derived lipid bilayer and Nucleocapsid (N) interacts with the RNA viral genome present at the core of the brain. (B) A schematic overview of the SARS-CoV-2 genome structure. *Showing mutation hotspots across the genome.

Figure 3

Phylogenetic relationships of SARS-CoV-2 clades, as defined by Nextstrain (as of September 15, 2022) showing evolutionary relationships of SARS-CoV-2 viruses from the ongoing COVID-19 pandemic. The phylogeny is rooted relative to early samples from Wuhan.

Figure 4 (Continued)

Location of the reported mutations in different regions of the SARS-CoV-2 genome: (A) Representing amino acid position of ORFs in the SARS-CoV-2 genome, the ORFs are shown in different colors along with the amino acid position, (B) showing mutations in the genome of the Alpha variant, (C) showing mutations in the genome of the Beta variant, (D) showing mutations in the genome of the Gamma variant. (E) Location of mutations reported in various regions of the Delta and Delta-plus SARS-CoV-2 variant. The ORFs of the SARS-CoV-2 genome are represented with different colors and the mutation present on the ORF is indicated on the respective ORFs. (F) Location of mutations reported in various regions of the Omicron BA.1 and BA.2 SARS-CoV-2 variant. The ORFs of the SARS-CoV-2 genome are represented with different colors and the mutation present on the ORF is indicated on the respective ORFs.

Figure 5

The effect of key mutations of SARS-CoV-2 variants on virus transmission and immune susceptibility. (A) Key mutations on Alpha VOC involved in transmission and immune escape. (B) Key mutations on Beta VOC involved in transmission and immune escape. (C) Key mutations on Gamma VOC involved in transmission and immune escape. (D) Key mutations on Delta VOC involved in transmission and immune escape. (E) Key mutations on Omicron VOC involved in transmission and immune escape.