Abstract
BACKGROUND: Interactions between SARS-CoV-2, influenza virus, and respiratory syncytial virus (RSV) at the population level remain poorly understood. This study aimed to quantify potential interactions among these viruses and assess their influence on transmission dynamics. METHODS: We analyzed weekly surveillance data on SARS-CoV-2, influenza A and B viruses (IAV and IBV), and RSV from seven regions from October 2021 to May 2024. Distributed lag nonlinear models within a spatiotemporal Bayesian hierarchical framework were used to assess the exposure-lag-response associations among virus pairs. Additionally, we developed a two-pathogen, meta-population mechanistic transmission model to capture the co-epidemic dynamics of IAV and SARS-CoV-2, and to quantify the strength and duration of their bidirectional interactions. RESULTS: Among all virus pairs examined, a statistically significant association is identified only between IAV positivity and subsequent SARS-CoV-2 risk. When IAV positive rate percentile is between the 52nd and 88th percentiles, the relative risk (RR) of SARS-CoV-2 infection is significantly reduced. The lowest RR for SARS-CoV-2 (0.58, 95% CrI: 0.40-0.85) occurs at a 5-week lag when IAV positivity reaches the 70th percentile. The fitted mechanistic model using incidence data in Beijing shows that IAV infection substantially reduces infection to SARS-CoV-2 by 94.24% (95% CrI: 88.50%-99.24%), with the protective effect lasting 38.24 days (95% CrI: 35.50-41.29 days). Conversely, SARS-CoV-2 infection is associated with a slight increase in infection to IAV. CONCLUSIONS: Our findings indicate that IAV circulation may transiently reduce population-level infection to SARS-CoV-2, potential through ecological or immunological mechanisms.