DYNAMICS OF RHINOVIRUS SARS-COV-2 COINFECTIONS AND SUPERINFECTIONS IN HUMAN AIRWAY CULTURES REVEAL TYPE-DEPENDENT VIRAL INTERFERENCE

Coinfections between respiratory viruses are frequent but their outcomes are poorly understood. Rhinoviruses (RVs) and SARS-CoV-2 are two clinically relevant respiratory pathogens circulating year-round. We used differentiated human bronchial air-liquid interface (ALI) tissue cultures to study coinfections and staggered superinfections between SARS-CoV-2 BA.2 and two RVs (RV-A1, RV-A16). RV-A16 exerted strong and sustained interference on SARS-CoV-2 replication, whereas RV-A1 showed transient effects. SARS-CoV-2 had limited impact on RVs but persisted long-term despite interference. Superinfection demonstrated that pre-established infection with either virus reduced subsequent replication of the other. RNA-FISH revealed spatially distinct infection foci with few dual-infected cells. Although coinfections prolonged interferon and cytokine secretion, functional assays showed that SARS-CoV-2 BA.2 replication was resistant to IFN, in contrast to Wuhan strains. Pleconaril inhibition of RV-A16 spread reduced its interference, highlighting the role of viral spreading. These findings highlight the complexity of respiratory viral interactions and their potential influence on transmission dynamics during viral co-circulation.