The role of viral interference in shaping RSV epidemics following the 2009 H1N1 influenza pandemic.

Respiratory syncytial virus (RSV) primarily affects infants, young children, and older adults, with seasonal outbreaks in the United States (US) peaking around December or January. Despite the limited implementation of non-pharmaceutical interventions, disrupted RSV activity was observed in different countries following the 2009 influenza pandemic, suggesting possible viral interference from influenza. Although interactions between the influenza A/H1N1 pandemic virus and RSV have been demonstrated at an individual level, it remains unclear whether the disruption of RSV activity at the population level can be attributed to viral interference. In this work, we first evaluated changes in the timing and intensity of RSV activity across 10 regions of the US in the years following the 2009 influenza pandemic using dynamic time warping. We observed a reduction in RSV activity following the pandemic, which was associated with intensity of influenza activity in the region. We then developed an age-stratified, two-pathogen model to examine various hypotheses regarding viral interference mechanisms. Based on our model estimates, we identified three mechanisms through which influenza infections could interfere with RSV: 1) reducing susceptibility to RSV coinfection; 2) shortening the RSV infectious period in coinfected individuals; and 3) reducing RSV infectivity in coinfection. Our study offers statistical support for the occurrence of atypical RSV seasons following the 2009 influenza pandemic. Our work also offers new insights into the mechanisms of viral interference that contribute to disruptions in RSV epidemics and provides a model-fitting framework that enables the analysis of new surveillance data for studying viral interference at the population level.