Omicron variant, scripting the end of the pandemic: An in silico analysis of SARS-CoV-2 genomic sequences and their epidemiological correlates (Preprint)

Abstract

A newly emerged SARS-CoV-2 variant B.1.1.529 worried the health policy makers worldwide due to a large number of mutations in its genomic sequence, especially in the spike protein region. World Health Organization (WHO) designated it as a global variant of concern (VOC) and was named 'Omicron.' Following Omicron's emergence, a surge in new COVID-19 cases was reported globally, primarily in South Africa (SA).

We aimed to understand whether the Omicron had an epidemiological advantage over existing variants.

We performed an in silico analysis of the complete genomic sequences of Omicron available on GISAID to analyze the functional impact of the mutations present in this variant on virus-host interactions in terms of viral transmissibility, virulence/lethality, and immune escape. In addition, we performed a correlation analysis of the relative proportion of the genomic sequences of specific SARS-CoV-2 variants (in the period of 01 Oct-29 Nov 2021) with the matched epidemiological data (new COVID-19 cases and deaths) from SA.

Compared to the current list of global VOCs/VOIs (as per WHO), Omicron bears more sequence variation, specifically in the spike protein and host receptor-binding motif (RBM). Omicron showed the closest nucleotide and protein sequence homology with the Alpha variant for the complete sequence and RBM. The mutations were found primarily condensed in the spike region (28-48) of the virus. Further, the mutational analysis showed enrichment for the mutations decreasing ACE2-binding affinity and RBD protein expression, in contrast, increasing the propensity of immune escape. An inverse correlation of Omicron with Delta variant was noted (r=-0.99, p< .001, 95% CI: -0.99 to -0.97) in the sequences reported from SA post-emergence of the new variant, later showing a decrease. There was a steep rise in the new COVID-19 cases in parallel with the increase in the proportion of Omicron since the first case (74-100%). In contrary, the incidences of new deaths was not increased (r=-0.04, p>0.05, 95% CI =-0.52 to 0.58).

In silico analysis of the viral genomic sequences suggest that the Omicron variant has more remarkable immune escape ability than the existing VOCs/VOIs, including Delta, but lesser virulence/lethality than other reported variants. The higher power for immune escape for Omicron was a likely reason for the surge in COVID-19 cases and soon becoming a globally dominant strain. They were more infectious but less lethal than the existing variants, hence outpaced them, thus scripting the pandemic's downfall.