Human Behavior and Built Environments Shape Influenza Seasonality in the US

Respiratory disease seasonality is widely recognized, yet its mechanistic basis remains poorly understood. Winter environmental conditions have dominated explanations for influenza seasonality in temperate regions, while human behavior's role has been overlooked. Integrating high-resolution data on influenza cases and human behavior in built environments, we show US influenza seasonality emerges from behavioral adaptations to the environment rather than environmental effects alone. Southeastern US counties maintain persistent summer circulation shaped by weather-driven indoor crowding and built environment vulnerabilities, seeding epidemics as early as August that then spread nationwide. A transmission model incorporating intercounty connectivity, school calendars, and building-modulated transmissibility reproduces this spatiotemporal invasion pattern. These results suggest behavior, both routine mixing and environmental adaptation, shapes influenza seasonality, complementing explanations centered on aerosol persistence or viral survival. Our framework supports epidemic preparedness: modeling southern reservoirs' connectivity to northern counties, shifting vaccination timing to precede local epidemic onset could reduce influenza burden.