The impact of RSV/SARS-CoV-2 co-infection on clinical disease and viral replication: insights from a BALB/c mouse model

RSV and SARS-CoV-2 are prone to co-infection with other respiratory viruses. In this study, we use RSV/SARS-CoV-2 co-infection to evaluate changes to clinical disease and viral replication in vivo. To consider the severity of RSV infection, effect of sequential infection, and the impact of infection timing, mice were co-infected with varying doses and timing. Compared with a single infection of RSV or SARS-CoV-2, the co-infection of RSV/SARS-CoV-2 and the primary infection of RSV followed by SARS-CoV-2 results in protection from SARS-CoV-2-induced clinical disease and reduces SARS-CoV-2 replication. Co-infection also augmented RSV replication at early timepoints with only the low dose. Additionally, the sequential infection of RSV followed by SARS-CoV-2 led to improved RSV clearance regardless of viral load. However, SARS-CoV-2 infection followed by RSV results in enhanced SARS-CoV-2-induced disease while protecting from RSV-induced disease. SARS-CoV-2/RSV sequential infection also reduced RSV replication in the lung tissue, regardless of viral load. Collectively, these data suggest that RSV and SARS-CoV-2 co-infection may afford protection from or enhancement of disease based on variation in infection timing, viral infection order, and/or viral dose. In the pediatric population, understanding these infection dynamics will be critical to treat patients and mitigate disease outcomes. Author SummaryInfants and young children are commonly affected by respiratory viral co-infections. While RSV and SARS-CoV-2 are two of the most prevalent respiratory viruses, their co-infection rate in children remains surprisingly low. In this study, we investigate the impact of RSV/SARS-CoV-2 co-infection on clinical disease and viral replication using an animal model. The findings indicate that RSV infection either simultaneously or prior to SARS-CoV-2 infection in mice protect against SARS-CoV-2-induced clinical disease and viral replication. On the other hand, infection with SARS-CoV-2 followed by RSV results in worsening of SARS-CoV-2-induced clinical disease, but also protection from RSV-induced clinical disease. These results highlight a protective role for RSV exposure, given this occurs before infection with SARS-CoV-2. This knowledge could help guide vaccine recommendations in children and sets a basis for future mechanistic studies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=151 SRC="FIGDIR/small/542043v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@f37ec4org.highwire.dtl.DTLVardef@782a8org.highwire.dtl.DTLVardef@112f0f1org.highwire.dtl.DTLVardef@889107_HPS_FORMAT_FIGEXP M_FIG C_FIG