Importance: Recent reports have highlighted an intense influenza activity related to the circulation of the influenza A(H3N2) subclade k variant. There is no data available on the impact of the emergence of H3N2 subclade k on the severity of the 2025/2026 epidemic or on the clinical phenotype of patients requiring admission to the intensive care unit (ICU).
Objective: To compare the clinical presentation, hospital mortality and virological characteristics of patients with laboratory-confirmed influenza infection included in French intensive care units during the 2025/2026 epidemic season with those of patients admitted during the 2024/2025 season. We also aimed at measuring the impact of the A(H3N2) subtype on hospital mortality during the 2025/2026 season.
Design: Prospective, multicenter, observational SEVARVIR cohort study including patients admitted during the 2024/2025 and 2025/2026 influenza seasons.
Setting: Forty-two French ICUs Participants: Adult patients with laboratory-confirmed influenza infection Interventions: none Main Outcomes and Measures: The primary outcome measure was in-hospital mortality.
Results: Patients admitted in intensive care units for influenza in 2024/2025 (n=360) and 2025/2026 (n=325) were included in the French nationwide prospective multicentre SEVARVIR study. There was no significant difference in day28 mortality between the seasons (12.7%, n=45/355 vs 16.5% n=28/170; p=0.28). In the 2025-26 season, 49% had the A(H1N1) subtype and 51% the A(H3N2) subtype (k subclade: 77%). The univariable Cox analysis revealed that patients infected with A(H3N2) viruses were at greater risk of death over time. Multivariable Cox analysis revealed that during the 2025-2026 season, age (adjusted hazard ratio, aHR=1.05 [1.00;1.11]; p=0.046) and the clinical frailty scale (aHR=1.82 [1.26;2.72]; p=0.001) were associated with an increased risk of death. The A(H3N2) subtype was not associated with an increased risk of death (aHR=1.13 [0.32;4.51]; p=0.85). Phylogenetic analyses from our ICU cohort together with 300 contextual sequences from community-acquired influenza cases collected during the same period showed no clustering according to severity.
Conclusions and Relevance: This French national prospective observational study, found that the emergence of the influenza A(H3N2) subclade K was associated with an increased risk of death in univariable but not multivariable analysis, adjusting for host-related factors.