ABSTRACT
Aim: To understand the impact of influenza/RSV co-infection on clinical disease severity among COVID-19 patients. Methods: We conducted a systematic literature review of publications comparing the clinical severity between the co-infection group (i.e., influenza/RSV with SARS-CoV-2) and mono-infection group (i.e., SARS-CoV-2), using the following four outcomes: need or use of supplemental oxygen, intensive care unit (ICU) admission, mechanical ventilation and deaths. We summarized the results by clinical outcome and conducted random-effect meta-analyses, where applicable. Results: Twelve studies reporting a total of 7862 COVID-19 patients were included in the review. Influenza and SARS-CoV-2 co-infection was found to be associated with a higher risk of ICU admission (5 studies, OR: 2.09, 95% CI: 1.64-2.68) and mechanical ventilation (5 studies, OR: 2.31, 95% CI: 1.10-4.85). No significant association was found between influenza co-infection and need/use of supplemental oxygen or deaths among COVID-19 patients (4 studies, OR: 1.04, 95% CI: 0.37-2.95;11 studies, OR: 1.41, 95% CI: 0.65-3.08, respectively). For RSV co-infection, data were only sufficient to allow for analyses for the outcome of deaths, and no significant association was found between RSV co-infection and deaths among COVID-19 patients (3 studies, OR: 5.27, 95% CI: 0.58-47.87). Conclusions: Existing evidence suggests that co-infection with influenza might be associated with a 2-fold increase in the risk for ICU admission and for mechanical ventilation among COVID-19 patients whereas evidence is limited on the role of RSV co-infection. Co-infection with influenza does not increase the risk of death in COVID-19 patients.