A 15-year study of neuraminidase mutations and the increasing of S247N mutation in Spain

The therapeutic arsenal against influenza is extremely limited and resistance often arises due to the emergence of mutations, especially in the neuraminidase (NA) gene. This study aimed to evaluate the evolution of NA mutations over 15 years in Spain. To do so, we used the GISAID database from which we downloaded a total of 11,125 influenza A(H1N1)pdm09, A(H3N2), B/Victoria and B/Yamagata NA virus sequences, and analyzed the resistance mutations using FluSurver software. Our results showed that the occurrence of NA resistance mutations remained constant in the four viruses during the 15 seasons evaluated, being around 0.5-5 %. Most of the resistance was found in the A(H1N1)pdm09 subtype (around 70 %), especially from the 2023-2024 season onwards, when a significant increase in the occurrence of S247N mutation was observed. The occurrence of this type of mutation before 2022 was rare, but in the 2023-2024 season a total of 44 influenza viruses harboring S247N mutations were detected, while in the other years, only two cases were observed. Some studies have described a significant increase in this mutation over the past two seasons and although it appears to confer only slightly reduced inhibition to oseltamivir, its increase is noteworthy and should be a reason for increased their vigilance.