Longitudinal Landscape of Long Flu: Prolonged Influenza Complications Beyond Acute Respiratory Disease

This study aims to characterizing both the pre-existing conditions that increase susceptibility and the long-term, post-acute sequelae ("long flu") following influenza. A longitudinal cohort study was conducted using data from the FinnGen cohort of 429,209 individuals including 9,204 influenza cases. A disease-wide association study (DWAS) framework was employed, using Cox proportional hazards models adjusted for age and sex to analyze 110 influenza-comorbid clinical endpoints. Pre-existing conditions, most notably cardiovascular diseases such as heart failure, coronary atherosclerosis, atrial fibrillation, and stroke, were significantly associated with an increased likelihood of a subsequent influenza diagnosis. Following influenza, individuals had a substantially elevated risk for a durable, multi-system "long flu" syndrome. The most robust and persistent risks were for new-onset cardiovascular and neurological diseases. Risks for thromboembolic events, heart failure, atrial fibrillation, stroke, and myocardial infarction remained significantly elevated for one to five years following influenza. Similarly, influenza was associated with a long-term increased incidence of neurodegenerative disorders, including migraine (with and without aura), Alzheimer's disease, and dementia. These findings underscore the urgent need to intensify preventive strategies, particularly through targeted vaccination of at-risk individuals, and to develop integrated care pathways to manage the multi-organ sequelae of long flu.