Could seasonal influenza vaccination influence COVID-19 risk?

De wals, P.; Divangahi, M.

Background: With possible resurgence of the SARS-CoV-2 and low seasonal influenza virus circulation next winter, reviewing evidence on a possible interaction between influenza vaccination and COVID-19 risk is important. Objective: To review studies on the effect of influenza vaccines on non-influenza respiratory disease (NIRD). Methods: Using different search strategies, 18 relevant studies were identified and their strength, limitations and significance were assessed. Results: Analysis of 4 RCT datasets did not suggest increased NIRD risk in recipients of live-attenuated vaccines (LAIV) and results of a cohort study suggested short-term protection consistent with the hypothesis of trained immunity. One RCT, four cohort studies and one test-negative case-control suggested increased NIRD risk in recipients of inactivated influenza vaccines (IIV), whereas five test-negative case-control studies did not show an increased risk associated with a specific viral pathogen. Cross-protection against COVID-19 was suggested in one cross-sectional study on IIV but major biases could not be excluded. Results of four recent ecological studies on COVID-19 were challenging to interpret. Conclusions: Available data on LAIV are reassuring but not all those on IIV. A drastic reorientation of 2020-2021 influenza campaigns is probably not warranted but studies aiming to test COVID-19 risk modification among recipients of seasonal influenza vaccines should be planned and funded.