Detection of D222G/N Mutations in Fatal Cases in A(H1N1)pdm09 Influenza Viruses Dominant in the 2024–2025 Season in the Russian Federation

Introduction: Seasonal influenza circulates in an epidemic pattern, with periodic shifts in the dominant subtype driven by antigenic drift and population immunity. Mutations in surface proteins – particularly within the hemagglutinin receptor-binding site (RBS) – enable the virus to evade host immune responses. Among these, the D222G/N substitution has been associated with increased virulence of A(H1N1)pdm09 viruses.

Objective: Genetic characterization of viruses detected in influenza cases in the Russian Federation in the 2024–2025 epidemic season.

Materials and methods: From September 10, 2024, to June 19, 2025, 1,931 specimens from patients with influenza, including 240 autopsy samples, were tested by RT-PCR. For 420 samples with sufficient genetic material, influenza virus genome sequences were obtained using NGS.

Results: During the 2024–2025 flu season, A(H1N1)pdm09 viruses predominated in the Russian Federation. Influenza B/Victoria lineage viruses were less frequent while influenza A (H3N2) cases were sporadic. Most fatal cases occurred in individuals belonging to risk groups, with a notably low vaccination coverage among them. Among fatal A(H1N1)pdm09 cases, the HA-D222N mutation – a marker of enhanced virulence – was detected in the major viral variant in 19.0 % of sequenced samples. Additionally, D222G/N mutations were identified in minor variants in 10.1 % of fatal cases. Notably, the D222N mutation in the major variant was also found in one recovered A(H1N1)pdm09 case (0.5 %). Resistance markers to antiviral drugs – oseltamivir (1.9 %) and baloxavir marboxil (0.4 %) were detected in 6 of all sequenced A(H1N1)pdm09 viruses (2.3 %).

Conclusion: The detection of HA-D222G/N mutations associated with increased virulence and fatality from A(H1N1)pdm09 viruses underscores the importance of vaccination as a key preventive measure, particularly for population groups at risk, and timely treatment for influenza.

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