Population immunity enhances the evolution of SARS-CoV-2 in Beijing revealed by wastewater genomic surveillance.

This study aims to elucidate the impact of population immunity on the regional evolution of SARS-CoV-2. A total of 3701 wastewater SARS-CoV-2 concentration values and 168 wastewater whole genomes of SARS-CoV-2 were obtained in Beijing over 11 months following the implementation of the "dynamic zero-COVID" policy adjustments in December 2022. The findings indicate that the number of variant strains identified through wastewater surveillance was 2.46 times greater than that detected by clinical monitoring, with single nucleotide polymorphisms showing an increase of up to 7.14 times. This enhanced surveillance facilitates a more comprehensive analysis of regional virus evolution patterns. Following the adjustment of epidemic measure, Beijing experienced three distinct waves of epidemics, and the dominant variant transitioned directly from BA.5 in the first wave to XBB after six months in the second one. During this period, strong population immunity formed by centralized infection in over 90 % of the population blocked the outbreak of internationally prevalent and concerning variants BQ.1 and CH.1.1, resulting in a 12.5 % faster regional evolution of SARS-CoV-2 strains in Beijing compared to the international context. Subsequently, in August 2023, EG.5 became the dominant variant in the third wave, aligning with international trends. The epidemics in Beijing have caused significant positive selection pressure on SARS-CoV-2 strains, favoring those with enhanced antigenic escape mutations in spike gene. These results underscore that the extensive infection after the adjustment of epidemic prevention policies has accelerated the evolution of SARS-CoV-2 in Beijing and been conducive to antigenic escape evolution, which can effectively inform decision making for epidemic control and preemptive vaccine design.