Omicron BA.2 lineage predominance in severe acute respiratory syndrome coronavirus 2 positive cases during the third wave in North India

Abstract

Background: Recent studies on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reveal that Omicron variant BA.1 and sub-lineages have revived the concern over resistance to antiviral drugs and vaccine-induced immunity. The present study aims to analyze the clinical profile and genome characterization of the SARS-CoV-2 variant in eastern Uttar Pradesh (UP), North India.

Methods: Whole-genome sequencing (WGS) was conducted for 146 SARS-CoV-2 samples obtained from individuals who tested coronavirus disease 2019 (COVID-19) positive between the period of 1 January 2022 and 24 February 2022, from three districts of eastern UP. The details regarding clinical and hospitalized status were captured through telephonic interviews after obtaining verbal informed consent. A maximum-likelihood phylogenetic tree was created for evolutionary analysis using MEGA7.

Results: The mean age of study participants was 33.9 ± 13.1 years, with 73.5% accounting for male patients. Of the 98 cases contacted by telephone, 30 (30.6%) had a travel history (domestic/international), 16 (16.3%) reported having been infected with COVID-19 in past, 79 (80.6%) had symptoms, and seven had at least one comorbidity. Most of the sequences belonged to the Omicron variant, with BA.1 (6.2%), BA.1.1 (2.7%), BA.1.1.1 (0.7%), BA.1.1.7 (5.5%), BA.1.17.2 (0.7%), BA.1.18 (0.7%), BA.2 (30.8%), BA.2.10 (50.7%), BA.2.12 (0.7%), and B.1.617.2 (1.3%) lineages. BA.1 and BA.1.1 strains possess signature spike mutations S:A67V, S:T95I, S:R346K, S:S371L, S:G446S, S:G496S, S:T547K, S:N856K, and S:L981F, and BA.2 contains S:V213G, S:T376A, and S:D405N. Notably, ins214EPE (S1- N-Terminal domain) mutation was found in a significant number of Omicron BA.1 and sub-lineages. The overall Omicron BA.2 lineage was observed in 79.5% of women and 83.2% of men.

Conclusion: The current study showed a predominance of the Omicron BA.2 variant outcompeting the BA.1 over a period in eastern UP. Most of the cases had a breakthrough infection following the recommended two doses of vaccine with four in five cases being symptomatic. There is a need to further explore the immune evasion properties of the Omicron variant.

Keywords: COVID-19; SARS-CoV-2; omicron; third wave; variant of concern (VOC); whole-genome sequencing (WGS).

FIGURE 1

A neighbor-joining (NJ) tree from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequences was generated using a Tamura 3-parameter model with gamma distribution and a bootstrap replication of 1,000 cycles. The whole-genome sequences of other SARS-CoV-2 variants deposited in GISAID used in this study are marked in black, and the reference isolate of Wuhan-HU-1 (accession no: NC 045512) is marked in red color.

FIGURE 2

CLC genomics analysis of the mutational changes in the BA.1 and sub-lineages of the Omicron variant. The scale representing the frequency of residue changes from least (Blue) to highest (Red). S, spike protein; E, envelope protein; M, membrane protein; N, nucleocapsid protein.

FIGURE 3

CLC genomics showing the mutational changes in the sub-lineage BA.2 and BA.2.10 of the Omicron variant. The scale representing the frequency of residue changes from least (Blue) to highest (Red). S, spike protein; E, envelope protein; M, membrane protein; N, nucleocapsid protein.

FIGURE 4

The Venn diagram shows shared mutations in the spike protein mutations of the BA.1, BA.1.1, BA.1.1.7, BA.2, and BA.2.10 lineages in Omicron variants of this study (https://bioinformatics.psb.ugent.be/webtools/Venn/).

FIGURE 5

A sequence logo representation of the RBD region of major Omicron variant spike protein in which letter height reflects the likelihood of finding a particular residue in that position. Residues are colored according to hydrophobicity (orange—hydrophobic, blue—basic, red—acidic, purple—neutral, green—polar).