Genomic Insights into Vaccine Evasion: A Cross-sectional Study from a Tertiary Care Hospital of Northern India

Introduction: Coronavirus Disease-2019 (COVID-19) vaccines are a crucial tool in controlling and ultimately ending the pandemic, complementing other preventive measures. India launched its vaccination campaign on January 16, 2021, initially using two vaccines that received emergency authorisation: Covaxin (BBV152) and Covishield (ChAdOx1 nCoV-19). The vaccination effort began with elderly individuals (60+ years) and frontline workers, eventually expanding to include various age groups. During this period, India faced a severe second wave of COVID19, marked by a notable rise in postvaccination breakthrough infections throughout 2021, driven by more transmissible and potentially more immune-evasive variants. To date, no study is available that details the rate of these breakthrough infections and the variants responsible in our region. Aim: To determine the rate of breakthrough infections in our region and identify which Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) variants are responsible for these infections. Materials and Methods: This cross-sectional study was conducted in a tertiary care hospital in Northern India over one year, from January 2021 to December 2021. Nasopharyngeal swabs from suspected COVID-19 patients were collected and subjected to Ribonucleic acid (RNA) extraction, followed by Reverse Transcription-Polymerase Chain Reaction (RTPCR) testing. The breakthrough infection rate was defined as infections occurring in individuals who were fully vaccinated with two standard doses of the AZD1222/Covishield vaccine. Genome sequencing was performed to identify the SARSCoV-2 variants responsible for postvaccination breakthrough infections. Data analysis was conducted using Microsoft Excel Software 16. Results: Between January 2021 and December 2021, 513,197 nasopharyngeal swabs were analysed, with a total of 32,952 (6.42%) samples testing positive for SARS-CoV-2 by RT-PCR. Out of these, 2,043 (6.2%) samples were from cases in which individuals had been vaccinated with two doses of the vaccine. Genome sequencing of 11 such samples revealed that eight of the patients were infected with the Delta variant (Pango Lineage: B.1.617.2). One sample showed the Eta variant (Lineage B.1.575) with the E484K mutation. Unfortunately, two samples could not be processed due to inadequate quality. Conclusion: A breakthrough infection rate of 6.2% was recorded, with the Delta variant (Pango Lineage: B.1.617.2) of SARS-CoV-2 being commonly associated with these infections. This study underscores the need for continued and rigorous genomic surveillance of emerging SARS-CoV-2 variants to assess their potential to evade immune responses.