SARS-CoV-2 Mutations Responsible for Immune Evasion Leading to Breakthrough Infection

Cureus. 2022 Sep 24;14(9):e29544. doi: 10.7759/cureus.29544. eCollection 2022 Sep.

Abstract

Background and objectives: India had faced a devastating second outbreak of COVID-19 infection, in which a majority of the viral sequences were found to be of the B.1.617.2 lineage (Delta-variant). While India and the world focused on vaccination, reports of vaccine-immunity evasion by the virus, termed "breakthrough cases", emerged worldwide. Our study was focused on the primary objective to identify the mutations associated with breakthrough infections SARS-CoV-2.

Methods: In our study, we extracted the SARS-CoV-2 RNA (ribonucleic acid) from reverse transcription-polymerase chain reaction (RT-PCR) positive COVID-19 patients, and 150 random samples were sent for sequencing to the Centre for Cellular & Molecular Biology, Hyderabad. Whole genome sequences of 150 SARS-CoV-2 viral samples were analyzed thoroughly. We mostly found B.1.617 and its sub-lineages in the genomic sequencing results.

Results and interpretation: On further analysis of patient data, it was seen that nine patients had been vaccinated against the SARS-CoV-2 previously. These nine patients had B.1.617/B.1 or A strains, and all of them had similar genomic variations in spike proteins as well as non-structural proteins (NSPs). The mutations seen in these sequences in the Spike (S), NSPs, and open reading frame (ORF) regions would have produced amino acid changes known to improve viral replication, confer drug resistance, influence host-cell interaction, and lead to antigenic drift.

Conclusions: Increased virulence culminating in vaccine immunity evasion may be inferred from these specific mutations. Our study adds to the growing body of evidence linking rapidly emerging mutations in the S (Spike) and ORF genes of the SARS-CoV-2 genome to immune evasion.

Keywords: b.1.617.2 (delta-variant); breakthrough infection; covid-19 retro; immune evasion; next genome sequencing; sars-cov-2.

Grants and funding

Funding required for this study was made available by Banaras Hindu University under a seed grant for new faculties under IoE to Dr. Chetan Sahni. The letter number is "R/Dev/D/IoE/Equipment/Seed Grant-II/2O22-23/48676", dated 07.06.2022.