Enhanced Recombination Among SARS-CoV-2 Omicron Variants Contributes to Viral Immune Escape

ABSTRACT SARS-CoV-2 virus evolution occurs as a result of antigenic drift and shift. Although antigenic drift has been extensively studied, antigenic shift, which for SARS-CoV-2 occurs through genetic recombination, has been examined scarcely. To gain a better understanding of the emergence and prevalence of recombinant SARS-CoV-2 lineages through time and space, we analyzed SARS-CoV-2 genome sequences from public databases. Our study revealed an extraordinary increase in the emergence of SARS-CoV-2 recombinant lineages during the Omicron wave, particularly in Northern America and Europe. This phenomenon was independent of sequencing density or genetic diversity of circulating SARS-CoV-2 strains. In SARS-CoV-2 genomes, recombination breakpoints were found to be more concentrated in the 3’ UTR followed by ORF1a. Additionally, we noted enrichment of certain amino acids in the spike protein of recombinant lineages, which have been reported to confer immune escape from neutralizing antibodies, increase ACE2 receptor binding, and enhance viral transmission in some cases. Overall, we report an important and timely observation of accelerated recombination in the currently circulating Omicron variants and explore their potential contribution to viral fitness, particularly immune escape.