Impact of Coinfection With SARS-CoV-2 and Influenza on Disease Severity: A Systematic Review and Meta-Analysis

Background: Although coinfection with influenza in COVID-19 patients has drawn considerable attention, it is still not completely understood whether simultaneously infected with these two viruses influences disease severity. We therefore aimed to estimate the impact of coinfected with SARS-CoV-2 and influenza on the disease outcomes compared with the single infection of SARS-CoV-2. Materials and Methods: We searched the PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure Database (CNKI) to identify relevant articles up to July 9, 2021. Studies that assessed the effect of SARS-CoV-2 and influenza coinfection on disease outcomes or those with sufficient data to calculate risk factors were included. Risk effects were pooled using fixed or random effects model. Results: We ultimately identified 12 studies with 9,498 patients to evaluate the risk effects of SARS-CoV-2 and influenza coinfection on disease severity. Results indicated that coinfection was not significantly associated with mortality (OR = 0.85, 95%CI: 0.51, 1.43; p = 0.55, I(2) = 76.00%). However, mortality was found significantly decreased in the studies from China (OR = 0.51, 95%CI: 0.39, 0.68; I(2) = 26.50%), while significantly increased outside China (OR = 1.56, 95%CI: 1.12, 2.19; I(2) = 1.00%). Moreover, a lower risk for critical outcomes was detected among coinfection patients (OR = 0.64, 95%CI: 0.43, 0.97; p = 0.04, I(2) = 0.00%). Additionally, coinfection patients presented different laboratory indexes compared with the single SARS-CoV-2 infection, including lymphocyte counts and APTT. Conclusion: Our study revealed that coinfection with SARS-CoV-2 and influenza had no effect on overall mortality. However, risk for critical outcomes was lower in coinfection patients and different associations were detected in the studies from different regions and specific laboratory indexes. Further studies on influenza strains and the order of infection were warranted. Systematic testing for influenza coinfection in COVID-19 patients and influenza vaccination should be recommended.