Interactions between SARS-CoV-2 and Influenza and the impact of coinfection on disease severity: A test negative design

Background The potential impact of COVID-19 alongside influenza on morbidity, mortality and health service capacity is a major concern as the Northern Hemisphere winter approaches. This study investigates the interaction between influenza and COVID-19 during the latter part of the 2019-20 influenza season in England. Methods Individuals tested for influenza and SARS-CoV-2 were extracted from national surveillance systems between 20/01/2020 and 25/04/2020. To estimate influenza infection on the risk of SARS-CoV-2 infection, univariable and multivariable analyses on the odds of SARS-CoV-2 in those who tested positive for influenza compared to those who tested negative for influenza. To assess whether a coinfection was associated with severe SARS-CoV-2 outcome, univariable and multivariable analyses on the odds of death adjusted for age, sex, ethnicity, comorbidity and coinfection status. Findings The risk of testing positive for SARS-CoV-2 was 58% lower among influenza positive cases, suggesting possible pathogenic competition between the two viruses. Patients with a coinfection had a risk of death of 5.92 (95% CI, 3.21-10.91) times greater than among those with neither influenza nor SARS-CoV-2 and 2.27 (95% CI, 1.23 to 4.19) greater than COVID alone suggesting possible synergistic effects in coinfected individuals. The odds of ventilator use or death and ICU admission or death was greatest among coinfection patients showing strong evidence of an interaction effect compared to SARS-CoV-2/influenza acting independently. Interpretation Cocirculation of these viruses could have a significant impact on morbidity, mortality and health service demand. Testing for influenza alongside SARS-CoV-2 and maximising influenza vaccine uptake should be prioritised to mitigate these risks. Funding This study was funded by Public Health England