Comprehensive detection and dissection of interlineage recombination events in the SARS-CoV-2 pandemic

Abstract The emergence and spread of the XBB lineage, a recombinant of SARS-CoV-2 omicron sublineages, has recently raised great concern for viral recombination globally. Since the COVID-19 outbreak, several recombination detection methods have been developed, and some interlineage recombinants have been reported. However, a comprehensive landscape for SARS-CoV-2 recombinants globally and their evolutionary mechanisms is still lacking. Here, we developed a lightweight method called CovRecomb based on lineage-specific feature mutations to detect and dissect interlineage SARS-CoV-2 recombinants quickly and precisely. By assessing over 14.5 million SARS-CoV-2 genomes, 135,567 putative recombinants were identified from 1,451 independent recombination events, 208 of which showed across-country, continental or global transmission. More than half of the manually curated recombinants could be systematically and automatically identified. Recombination breakpoints were distributed throughout the SARS-CoV-2 genome, while hotspots were inferred in six regions, especially in the second halves of the N-terminal domain and receptor-binding domain of spike genome. Epidemiological analyses revealed that recombination events occurred extensively among different SARS-CoV-2 (sub)lineages and were independent of the prevalence frequency of lineages.