Challenges in defining severe influenza with implications for measuring and communicating influenza vaccine effects

With declining influenza vaccine coverage since the COVID-19 pandemic, it is more critical than ever to provide a strong evidence base to support the benefits of influenza vaccination. Influenza vaccination can reduce the risk of influenza-associated outpatient visits and hospitalizations, but some studies have also shown that influenza vaccination can decrease the severity of disease among those who develop influenza illness despite vaccination. Yet, using observational real-world data to demonstrate these benefits is challenging. In this commentary, we outline some of the challenges and issues to consider when designing observational studies to demonstrate the benefits of influenza vaccination among patients hospitalized with influenza. We further provide suggestions for how to create more standardized definitions for severe and critical influenza outcomes against which vaccine benefits may be measured, using lessons learned from the COVID-19 pandemic.