Abstract
<jats:p>Until 2020, two lineages of the influenza B virus had co-circulated globally. Measures to control the COVID-19 pandemic led to a near-absence of influenza infections. While B/Victoria reemerged in late 2021, there have been no reports of B/Yamagata since the pandemic. To investigate which epidemiological and immunological factors were primarily responsible for the extinction of B/Yamagata, we developed a global model for the two influenza B lineages. To mimic the transmission impacts of the pandemic, we implemented a transient reduction in contacts and identified parameter values that recapitulated viral coexistence dynamic before the pandemic and the qualitative post-pandemic outcomes of B/Victoria (reemergence in late 2021) and B/Yamagata (extinction). Our results suggest that, rather than immunological or evolutionary mechanisms, the extinction of B/Yamagata was mainly driven by its lower basic reproduction number making the virus particularly vulnerable during the early phase of the pandemic. Stochastic simulations of our best-fitting model suggest that B/Victoria was also close to extinction during this period. We investigate the model to assess the feasibility of B/Victoria eradication through vaccination and the potential for a sustained re-emergence of B/Yamagata in the 2026-27 flu season, thus highlighting important considerations for biosafety.</jats:p> <jats:sec> <jats:title>Significance</jats:title> <jats:p>For decades, the Yamagata and Victoria lineages of the influenza B virus co-circulated globally, causing millions of infections in humans. Only Victoria reemerged after the COVID-19 pandemic. By combining mechanistic transmission modeling with worldwide influenza surveillance data, we show that Yamagata’s extinction is most consistent with a lower intrinsic transmissibility than that of the surviving Victoria lineage. Contrary to other proposed explanations, differences in cross-immunity and immune escape appear insufficient to explain the observed outcome. Our analyses further indicate that Victoria narrowly avoided extinction during the COVID-19 disruption, but now transmission of Yamagata would be sustained if the lineage were reintroduced. These results inform both influenza eradication efforts and biosafety policy.</jats:p> </jats:sec>