Zandra Felix Garza, Dirk Eggink, Mariam Bagheri, Sharon van den Brink, Gabriel Goderski, Mark Pronk, Pascal Lexmond, Mariëtte Hooiveld, Rianne van Gageldonk-Lafeber, Björn Koel, Ron Fouchier, Adam Meijer
In 2023/24, A(H1N1)pdm09 influenza viruses with neuraminidase (NA)-S247N emerged in NA-clade C.5.3.3 carrying NA-I223V, spread internationally, then faded. Such double mutants reappeared sporadically in 2024/25. They expanded again in 2025/26 in NA-clade D.3 viruses carrying NA-S247N after acquiring NA-I223V in Europe - notably Spain, the Netherlands, Finland and France, and beyond. Dutch double mutants from both seasons showed median 12- and 13-fold reduced inhibition by oseltamivir. These findings underscore the need for ongoing genomic and phenotypic monitoring of antiviral susceptibility.