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.

Keywords: COVID-19; SARS-CoV-2 genome; alpha variant; ion torrent; kappa variant and delta variant; next generation sequencing.

Figure 1

Daily count of new COVID-19 cases reported from India between January 2021 through 16 April 2021, the stars represent the collection dates of the samples included in this study.

Figure 2

The prevalence of the α, Kappa and Delta variant illustrated in terms of the sequences of samples collected from September 2020 till the date in GISAID.

Figure 3

(a) The percentage of sequences of α, Kappa and Delta variant submitted in GISAID for clinical samples collected from February 2021 to March 2021 from India; (b) average increase of new cases in Maharashtra and rest of the India during the same period, relative to figures of 1 February 2021.

Figure 4

Principal Component Analysis of the 20 sequenced samples.

Figure 5

Maximum Likelihood phylogenetic tree showing the relationship of the 20 samples of SARS-CoV-2 strains in this study in the context of globally circulating strains of SARS-CoV-2.

Figure 6

(a) Gene-wise depiction of number of mutations and mutation frequency in 20 sequenced samples; (b) clade wise mutation distribution in sequenced samples; (c) amino-acid mutations observed in SARS-CoV-2 genome in sequenced samples.

Figure 7

Mutation distribution among the sequenced samples belonging to the kappa variant.