Investigating the influence of virus-virus interactions on susceptibility to subsequent infections

The co-circulation of multiple respiratory pathogens can lead to competitive or cooperative forms of pathogen–pathogen interactions through broad-acting innate or adaptive immunity leading to enhanced or reduced risk of subsequent infections. Methods: We retrospectively analyzed 6,396 unique individuals from the Seattle Flu Study to investigate viral interference among six respiratory pathogens. Using longitudinal data collected from March 2020 to July 2022, we assessed respiratory virus interference effects in the Seattle metropolitan area. Statistical analysis included investigating viral circulation proportion, Cox regression modeling to calculate the hazard risk of subsequent viral detection, and mixed effects modeling to assess associations between primary respiratory infection onset and viral load via cycle threshold (Ct) of subsequent infections. Results: Surveillance of the Seattle metropolitan area revealed persistent circulation of human rhinovirus (13.0% of samples positive), SARS-CoV-2 (3.6%), and adenoviruses (1.23%) with a reduction in detection of other pathogens after COVID-19 mitigation efforts began in March 2020. The risk of subsequent infections varied by pathogen and time since primary detection. Significance was observed for human rhinovirus, SARS-CoV-2, adenoviruses, and respiratory syncytial virus. A significant reduction of secondary detection (HR; 0.20-0.61) within the 0-14 risk period after primary virus detection, a significantly lower risk of subsequent infection after 60 days (HR; 0.20-0.60) and a non-significant higher risk of subsequent infection within 14-30 day risk period was observed. Conclusions: Primary virus detection was associated with a lower risk of subsequent virus detection within the first 14 and following 60 days and a higher risk within 14-30 days after primary infection. Results provide insights into viral dynamics, aiding public health strategies.