Enhanced recombination among Omicron subvariants of SARS‐CoV‐2 contributes to viral immune escape

Abstract Genetic recombination is an important driver of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) evolution, which requires the coinfection of a single host cell with different SARS‐CoV‐2 strains. To understand the emergence and prevalence of recombinant SARS‐CoV‐2 lineages through time and space, we analyzed SARS‐CoV‐2 genome sequences collected from November 2019 to July 2022. We observed 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 the sequencing frequency or genetic diversity of circulating SARS‐CoV‐2 strains. The recombination breakpoints were more prevalent in the 3′‐untranslated region of the viral genome. Importantly, we noted the enrichment of certain amino acids in the Spike protein of recombinant lineages, which have been reported to confer immune escape from neutralizing antibodies and increase angiotensin‐converting enzyme 2 receptor binding in some cases. We also observed I42V amino acid change genetically fixated in the NSP14 of the Omicron lineage, which needs further characterization for its potential role in enhanced recombination. Overall, we report the important and timely observation of accelerated recombination in the currently circulating SARS‐CoV‐2 Omicron variants and explore their potential contribution to viral fitness, particularly immune escape.