Genomic epidemiology of influenza B circulation in China during prolonged border closure from 2020 to 2021

Abstract China experienced a resurgence of seasonal influenza activity throughout 2021 under intermittent control measures and prolonged international border closure. We show genomic evidence for multiple A(H3N2), A(H1N1), and B/Victoria transmission lineages circulating for over three years, with the 2021 resurgence driven by two B/Victoria clades. Novel hemagglutinin (HA) gene mutations and altered age profiles of infected individuals were observed, and Jiangxi province was identified as a major source for nationwide outbreaks. An increase in the effective population size and effective reproduction number of B/Victoria outbreaks followed major national holidays, several months prior to their initial detection, underscoring the importance of influenza vaccination prior to holiday periods or travel. Clade 3a2 B/Victoria viruses with the HA1 mutation H122Q and a distinct gene constellation are becoming increasingly dominant in China and warrant close monitoring due to poor antigenicity match with current vaccine strains.