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.

Significance of wastewater surveillance in detecting the prevalence of SARS-CoV-2 variants and other respiratory viruses in the community – A multi-site evaluation

“…[ 39 ] Furthermore, BA.2.12.1 has been observed to overcome immunity from earlier Omicron infections, suggesting that it may cause re-infections and increase infectivity. [ 40 , 41 ] In our TMWRF samples, which represent the most extensive collection area, BA.2.12.1 was detected seven weeks prior to the first sample containing BA.5. Although sample collection dates at non-TMWRF sites are limited, we did see BA.2.12.1 as the predominant variant at two other sites (Sub-Neighborhood and Travel-Influenced Sites) preceding BA.5; however, BA.2.12.1 was predominant alongside BA.5 in two other sites (STMWRF, RSWRF) ( Fig.…”

Significance of Wastewater Surveillance in Detecting the Prevalence of SARS-CoV-2 Variants and Other Respiratory Viruses in the Community – A Multi-Site Evaluation

“…39 Furthermore, BA.2.12.1 has been observed to overcome immunity from earlier Omicron infections, suggesting that it may cause re-infections and increase infectivity. 40,41 In our TMWRF samples, which represent the most extensive collection area, BA.2.12.1 was detected seven weeks prior to the first sample containing BA.5. Although sample collection dates at non-TMWRF sites are limited, we did see BA.2.12.1 as the predominant variant at two other sites (Sub-Neighborhood and Travel-Influenced Sites) preceding BA.5; however, BA.2.12.1 was predominant alongside BA.5 in two other sites (STMWRF, RSWRF) (Figure 4).…”

Pathways to altered virulence of SARS-CoV-2

“…For example, a variant with the fusogenicity (and hence the IFR) of the Alpha or Delta variants and the transmissibility of the Omicron variants could have a profound acute mortality effect (193). Precedent already exists for recombination within Omicron lineages giving rise to variants with enhanced immune suppression and evasion (194). SARS-CoV-2 shares nearly 80% nucleotide identity with SARS-CoV-1, a virus with an estimated 10% IFR but with lower transmissibility and no observed asymptomatic transmission (195).…”