Assessing the Broader Impact of Influenza: A Meta-Analysis of Cause-Specific and All-Cause Influenza-Associated Mortality

Abstract The mortality impact of influenza epidemics is often quantified via increases in respiratory mortality, but this may not fully capture other health outcomes like cardiovascular events. We aimed to explore the ratios of influenza-associated cause-specific to all-cause mortality. We reviewed relevant articles from PubMed and EMBASE which reported both influenza- associated all-cause mortality and at least one death grouping: pneumonia and influenza, respiratory, or respiratory plus cardiovascular diseases. Only population-based estimates from influenza seasons were included. We included 130 mortality ratio estimates from 54 studies. We identified substantial heterogeneity in estimates (0.012-0.93). Higher ratio estimates were attributed to respiratory plus cardiovascular diseases (0.45-0.93) compared with respiratory diseases (0.078-0.66) or pneumonia and influenza (0.012-0.38). Respiratory mortality to all-cause mortality ratios increased substantially with age. Our review quantifies the broader mortality burden of influenza, with substantial impact associated with cardiovascular deaths in addition to influenza-associated respiratory deaths.