Relative Consolidation of the Kappa Variant Pre-Dates the Massive Second Wave of COVID-19 in India

Abstract

India experienced a tragic second wave after the end of March 2021, which was far more massive than the first wave and was driven by the emergence of the novel delta variant (B.1.617.2) of the SARS-CoV-2 virus. In this study, we explored the local and national landscape of the viral variants in the period immediately preceding the second wave to gain insight into the mechanism of emergence of the delta variant and thus improve our understanding of the causation of the second wave. We randomly selected 20 SARS-CoV-2 positive samples diagnosed in our lab between 3 February and 8 March 2021 and subjected them to whole genome sequencing. Nine of the 20 sequenced genomes were classified as kappa variant (B.1.617.1). The phylogenetic analysis of pan-India SARS-CoV-2 genome sequences also suggested the gradual replacement of the α variant with the kappa variant during this period. This relative consolidation of the kappa variant was significant, since it shared 3 of the 4 signature mutations (L452R, E484Q and P681R) observed in the spike protein of delta variant and thus was likely to be the precursor in its evolution. This study demonstrates the predominance of the kappa variant in the period immediately prior to the second wave and underscores its role as the “bridging variant” between the α and delta variants that drove the first and second waves of COVID-19 in India, respectively.

From Minor Mutant to Dominance, the Evolution of SARS-CoV-2 Variants

“…Lineage defining mutations that appeared first as minor mutations in local communities were also observed in India between November 2020 and May 2021 prior to the emergence of the Kappa (B.1.617.1) and Delta (B1.617.2) variants [39] [40]. A possible reason why the Indian subcontinent was so dramatically affected may have been the high prevalence of the A97V (SNP: C13730T) and P323L (SNP: C14408T) mutations in the RNA-dependent RNA polymerase (NSP12) on the subcontinent [39].…”

Interpretable and Predictive Deep Neural Network Modeling of the SARS-CoV-2 Spike Protein Sequence to Predict COVID-19 Disease Severity

“…Similarly E484Q has been a characteristic mutation in the Delta lineage, but E484K has been an aspect of other pre-Delta, such as Beta and some Alpha sublineages [ 70 , 71 , 72 ]. Similarly, P681H was found in the highly prevalent Alpha lineage [ 73 ], and P681R was found in the Kappa and then later Delta lineage [ 74 ]. Accordingly, it may be the case that a consistently high attention suggests that the model pays attention to the site because it was not a point of variation at early time points.…”

“…By contrast, another site with frequent mutations, site 484, where E484K, E484Q, and E484A mutations associated with antibody escape have been found [ 71 ], does not have high attention. The low attention at position 484 in the disease severity model may suggest that the site does not have a significant role in determining virulence rather than antibody evasion [ 26 , 70 , 72 , 73 , 74 ].…”

COVID-19 Genetic Variants and Their Potential Impact in Vaccine Development

“…The P681R mutation was located near the furin cleavage site, which may influence viral entry into the host cell. Among non-spike proteins, R203M was found in the N-protein, which could impact viral assembly [ 54 ]. The Kappa variant may have a higher tendency of escaping from vaccine-induced immunity than the Delta variant.…”