Influenza Vaccination and Disease Severity Among Older Adults Hospitalized with Influenza in France: A Nationwide Cohort Study, 2016-2024

Objective Seasonal influenza remains a major cause of severe morbidity and mortality among older adults, despite vaccine availability. We assessed whether influenza vaccination was associated with reduced disease severity among adults aged 65 years or more hospitalized with influenza in France. Methods and Analysis We conducted a nationwide retrospective cohort study using the French National Health Data System (SNDS). Adults aged 65 years or more hospitalized with confirmed influenza (ICD-10 codes: J09 or J10) between October 2016 and December 2024 were included, excluding 2020-2021. Vaccination status was identified from reimbursed community pharmacy dispensing records. Entropy balancing was used to balance sociodemographic characteristics, chronic conditions pneumococcal vaccination, and COVID-19 vaccination. Weighted regression models estimated adjusted risk ratios (aRRs) for invasive mechanical ventilation (IMV), intensive care unit (ICU) admission, in-hospital death, and a composite severe outcome. Multistate survival models assessed transitions specific hazard ratios (HR) between hospitalization, ICU, discharge, and in-hospital death. Results Among 132,443 influenza-associated hospitalizations, 72,852 (55%) occurred among vaccinated patients and 59,591 (45%) among unvaccinated patients. Vaccinated patients were older (mean age, 82.3 vs 79.3 years). IMV occurred in 2128 vaccinated (2.9%) and 2544 unvaccinated (4.3%) hospitalizations (aRR, 0.88; 95%CI: 0.83 to 0.93). In-hospital death occurred in 6300 (8.6%) and 4952 (8.3%), respectively (aRR, 0.90; 95%CI: 0.87 to 0.93). Vaccination was also associated with a lower risk of the composite outcome (aRR, 0.96; 95%CI: 0.94 to 0.98), but not ICU admission (aRR, 0.99; 95%CI: 0.96 to 1.01). Among patients admitted to ICU, vaccination was associated with a lower hazard of death (adjusted hazard ratio, 0.85; 95%CI: 0.78 to 0.92) and a 2-day reduction in the median time to discharge. Conclusion In this nationwide cohort study, influenza vaccination was associated with lower risks of IMV and in-hospital death among older adults hospitalized with influenza. These findings are consistent with possible attenuation of disease severity and support efforts to improve influenza vaccination among older adults.