Unraveling the mechanism behind the probable extinction of the B/Yamagata lineage of influenza B viruses

The COVID-19 pandemic caused an unprecedented disruption to the global circulation of influenza viruses. Among the most notable outcomes was the probable extinction of the B/Yamagata lineage of influenza B viruses, which has been rarely detected since March 2020. However, the underlying mechanism of the probable extinction is unknown. Here, we combine molecular, antigenic, and epidemiological data to explore the drivers of this phenomenon. Our analysis reveals that the probable extinction of B/Yamagata was driven by reduced transmission due to nonpharmaceutical interventions (NPIs) and a depleted susceptible population caused by conserved antigenicity and the 2017/2018 outbreak. Specifically, B/Yamagata exhibited slower antigenic evolution and alternating antigenic dominance compared to the co-circulating B/Victoria lineage, which was consistent with its weaker positive selection pressure. Simulation analysis suggests that B/Yamagata would maintain circulation if it underwent significant antigenic drift around the COVID-19 pandemic or if NPIs were not implemented. These findings provide a mechanistic explanation for the probable extinction of B/Yamagata and offer broader insights for controlling similar respiratory viruses.