Impact of co-infection with SARS-CoV-2 and other respiratory viruses on illness: Pooled analyses of 11 COVID-19 cohorts

Objective: This individual patient data meta-analysis investigates the impact of SARS-CoV-2 infection with or without other respiratory viruses on Acute Respiratory Illness (ARI) occurrence and severity. Methods: We pooled individual participant data from 11 prospective COVID-19 community and healthcare cohorts (2020–2024). A subject's first respiratory sample was tested for SARS-CoV-2 and a panel of respiratory viruses. The association of SARS-CoV-2 single versus viral co-infection with ARI occurrence and severity was analyzed using mixed effects regression. The analysis was repeated for Human Rhinovirus (HRV). Results: Of 1606 SARS-CoV-2 positive episodes (1597 subjects), 124 (7.7%) were co-infected with another respiratory virus, the majority with HRV (66.1%). SARS-CoV-2 Co-infection was associated with a lower odds of ARI than SARS-CoV-2 single infection in community cohorts (adjusted (a) OR: 0.39; 95%CI: 0.21–0.71). This association was not observed for ARI severity in healthcare cohorts (aOR: 1.76; 95%CI: 0.67–4.61). Co-infection versus single infection with HRV was associated with higher ARI occurrence and severity in both settings (community: aOR: 1.72 and healthcare: aOR: 6.04). Conclusion: In community settings, SARS-CoV-2 co-infection with another virus, particularly HRV, attenuates ARI compared to SARS-CoV-2 single infection. The low number of detected co-infections with other viruses, such as influenza or RSV, limits generalizability to other combinations of co-infecting viruses.