Population Density, Vaccination Coverage, and the Persistent Burden of Influenza Mortality in the United States 2252774

Abstract Introduction Seasonal influenza remains a leading cause of preventable morbidity and mortality despite decades of widespread vaccination. Annual reformulation of the influenza vaccine and variable uptake rates hinder consistent population-level protection. Understanding how vaccination coverage, population density, and susceptibility interact is essential to refining prevention strategies. Methods Using published national and state-level data from 1980—2019, we analyzed influenza-associated mortality across age groups and comorbidity profiles relative to annual vaccination coverage. We further evaluated 2017 influenza mortality in relation to population density and vaccine availability to assess geographic and demographic trends. Results Despite increasing vaccination rates from 1980 to 2019, influenza-related mortality among adults ≥65 years remained unchanged. No state or national herd immunity threshold was reached during this period. Vaccine supply growth lagged behind U.S. population expansion, limiting coverage sufficient for community-level protection. In 2017, the most populous states exhibited the highest influenza-related mortality burden; however, within these states, city density did not correlate with mortality rates. Influenza deaths were concentrated where susceptible populations resided, regardless of urban or rural classification. Conclusion Our findings indicate that current annual influenza vaccination strategies have not achieved herd immunity or reduced mortality among the most vulnerable populations. To substantially decrease influenza-related deaths, vaccination efforts must prioritize achieving herd immunity within the nation’s most populous states, where transmission potential and susceptible populations are greatest. Funding Source N/A Topic Categories Vaccines and Immunotherapy (VAC)