Emerging SARS-CoV-2 variants can potentially break set epidemiological barriers in COVID-19

Abstract

Young age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent coronavirus disease 2019 waves, which are believed to be driven by newer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS-CoV-2 variants have key mutations that can induce significant changes in the virus-host interactions. Recent studies report that, some of these mutations, singly or in a group, enhance key mechanisms, such as binding of the receptor-binding domain (RBD) of the viral spike protein with the angiotensin-converting enzyme 2 (ACE2) receptor in the host-cells, increase the glycosylation of spike protein at the antigenic sites, and enhance the proteolytic cleavage of the spike protein, thus leading to improved host-cell entry and the replication of the virus. The putative changes in the virus-host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS-CoV-2 infection and the disease outcomes are known to be influenced by host-cell expressions of ACE2 and other proteases. The new variants can act more efficiently, and even with the lesser availability of the viral entry-receptor and the associated proteases, can have more efficient host-cell entry and greater replication resulting in high viral loads and prolonged viral shedding, widespread tissue-injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence shows that multiple new variants have reduced neutralization by both, natural and vaccine-acquired antibodies, indicating that repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic.

Keywords: COVID-19; SARS-CoV-2 variants; epidemiology; mutation; pandemic; waves.

Figure 1

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2): host‐cell entry mechanisms. Entry of SARS‐CoV‐2 into host cell depends on binding of receptor‐binding domain (RBD) of viral spike (S) protein to the cell surface receptor angiotensin‐converting enzyme‐2 (ACE2). For a successful binding to ACE2, “S” protein is required to be cleaved by the host proteases, TMPRSS2 and Furin. Another host protease CTSL is involved in a pH‐dependent cleavage of the S protein inside the endosomes. The binding to ACE2 leads to endocytosis and allows for replication of the virus inside the host cell. The newly formed virions are released after bursting of the infected cell and spread further. Viral infection of the host‐cell subsequently leads to activation of innate host defense mechanism, recruitment of the immune cells by the infected tissue, and synthesis and release of the cytokines

Figure 2

Phylodynamics of emerging SARS‐CoV‐2 lineages across the globe. (Data source: GISAID Initiative (www.gisaid.org, accessed on November 1, 2021. The image is created using EpiCoV™ application using 3572 SARS‐CoV‐2 genomes sampled between December 2019 and October 2021.). SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 3

SARS‐CoV‐2 lineage specific mutations in spike protein regions. (Mutations with > 75% prevalence in at least one lineage are shown. Data source: www.outbreak.info, accessed on August 18, 2021). SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 4

SARS‐CoV‐2 lineage‐specific mutations in non‐spike protein regions. (Mutations with > 75% prevalence in at least one lineage are shown. Data source: www.outbreak.info, accessed on August 18, 2021).SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 5

Lineage specific mutations in spike protein regions of SARS‐CoV‐2 Delta plus variants. (Mutations with > 75% prevalence in at least one lineage are shown. Data source: www.outbreak.info, accessed on November 1, 2021). SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2

Figure 6

The global spread of emerging SARS‐CoV‐2 variants. (Data source: GISAID Initiative (www.gisaid.org, accessed on Nov 1, 2021. The image is created using EpiCoV™ application using 3572 SARS‐CoV‐2 genomes sampled between December 2019 and October 2021.). SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2