Estimating the range and duration of post-influenza symptoms, conditions and diseases

Abstract Background Acute symptoms of influenza are understood; however, less is known about potential post-acute sequelae. We conducted a retrospective matched cohort study to identify conditions with elevated risk following influenza. Methods We analyzed data from the Merative MarketScan Research Databases (2001–2019), including 3.3 million patients with a diagnosis of influenza. Cases were matched 1:1 to patients based on similar age, sex, care setting, and enrollment period with no influenza diagnosis. We examined the frequency of diagnosis codes in the year before and after the index influenza event, applying K-means clustering to identify diagnoses with post-influenza visit patterns similar to cough, a known sequela of influenza. Conditions were reviewed and aggregated into clinical categories. We compared trends in diagnoses between influenza cases and controls using a difference-in-differences approach. Results We identified 67 diagnostic categories with significantly increased incidence post-influenza infection. Both commonly known sequelae, such as pneumonia and otitis media as well as less expected findings, such as acute kidney failure and oral candidiasis were identified. The duration of elevated risk varied by condition, ranging from a week (e.g., rhabdomyolysis) to five weeks (e.g., hemoptysis) or eight weeks (e.g., chronic bronchitis). Conclusions We found that influenza is associated with conditions not typically considered. Also, some symptoms last longer than commonly appreciated, suggesting that some patients may suffer from a prolonged illness due to the influenza infection. Our findings have important implications for not only demonstrating the full burden of influenza but also informing future studies to prevent or treat influenza.