Abstract: | Epidemics of respiratory syncytial virus (RSV) are known to occur in wintertime in temperate countries including the United States, but there is a limited understanding of the importance of climatic drivers in determining the seasonality of RSV. In the United States, RSV activity is highly spatially structured, with seasonal peaks beginning in Florida in November through December and ending in the upper Midwest in February-March, and prolonged disease activity in the southeastern US. Using data on both age-specific hospitalizations and laboratory reports of RSV in the US, and employing a combination of statistical and mechanistic epidemic modeling, we examined the association between environmental variables and state-specific measures of RSV seasonality. Temperature, vapor pressure, precipitation, and potential evapotranspiration (PET) were significantly associated with the timing of RSV activity across states in univariate exploratory analyses. The amplitude and timing of seasonality in the transmission rate was significantly correlated with seasonal fluctuations in PET, and negatively correlated with mean vapor pressure, minimum temperature, and precipitation. States with low mean vapor pressure and the largest seasonal variation in PET tended to experience biennial patterns of RSV activity, with alternating years of “early-big” and “late-small” epidemics. Our model for the transmission dynamics of RSV was able to replicate these biennial transitions at higher amplitudes of seasonality in the transmission rate. This successfully connects environmental drivers to the epidemic dynamics of RSV; however, it does not fully explain why RSV activity begins in Florida, one of the warmest states, when RSV is a winter-seasonal pathogen. Understanding and predicting the seasonality of RSV is essential in determining the optimal timing of immunoprophylaxis. |