Clinical manifestations of adult patients requiring influenza-associated hospitalization in the pre-, during, and post-COVID-19 pandemic periods: An internet-based, prospective, multicenter, cohort study in Japan.

BACKGROUND: Influenza is a major concern, but it has been affected by the COVID-19 pandemic worldwide. The objective of this study was to clarify the differences in the clinical manifestations of severely ill patients infected with influenza in Japan among the pre-, during, and post-COVID-19 pandemic periods. METHODS: The clinical data of patients who were severely ill with influenza and required hospitalization were gathered and analyzed between September 2019 and August 2025 (6 influenza seasons) using an internet-based data-capture system, and the pre-(2019 season), during (2020, 2021, and 2022 seasons), and post- (2023 and 2024 seasons) COVID-19 pandemic periods were compared. RESULTS: A total of 490 patients were enrolled and analyzed, with 87 (17.8%), 21 (4.29%), and 382 (78.5%) patients in the pre-, during, and post-COVID-19 pandemic periods, with mortality of 2.3%, 0%, and 7.9%, respectively. Age, male/female ratio, underlying diseases, pneumonia rates, oxygen use, isolated bacteria, including Streptococcus pneumoniae, and anti-influenza agents were similar among the three groups. However, intrafamilial transmission was decreased, although the influenza vaccination rate and antibiotic use were decreased in the post-COVID-19 period. CONCLUSIONS: Influenza infection might be a greater issue after the COVID-19 pandemic because of the decreased vaccination rate and worse prognosis in the post-COVID-19 period. Although intrafamilial transmission and antibiotic use were decreased in the post-COVID-19 period, continuous nationwide surveillance and promotion of vaccination will be required to inhibit the increase of hospitalized and/or severe influenza patients.