The Association between Influenza Vaccination and COVID-19 and Its Outcomes: A Systematic Review and Meta-Analysis of Observational Studies

Influenza could circulate in parallel with COVID-19. In the context of COVID-19, some studies observed inverse associations between influenza vaccination and SARS-CoV-2 infection and clinical outcomes, while others did not. We conducted a meta-analysis to assess the association between influenza vaccination and SARS-CoV-2 infection and clinical outcomes, aiming to provide evidence for COVID-19 prevention and vaccination promotion. We searched four databases from inception to 10 March, 2021. Random effects and fixed effects models were used to pool odds ratios (ORs) and adjusted estimates with 95% confidence intervals (CIs). We used funnel plots to evaluate the publication bias, I2 statistics to evaluate the heterogeneity, and conducted subgroup analyses. Sixteen observational studies involving 290,327 participants were included. Influenza vaccination was associated with a lower risk of SARS-CoV-2 infection (pooled adjusted OR: 0.86, 95%CI: 0.81–0.91), while not significantly associated with adverse outcomes (intensive care: adjusted OR 0.63, 95%CI: 0.22–1.81; hospitalization: adjusted OR 0.74, 95%CI: 0.51–1.06; mortality: adjusted OR 0.89, 95%CI: 0.73–1.09). Our findings suggest that influenza vaccination is associated with a lower risk of SARS-CoV-2 infection. It is crucial for policy makers to implement strategies on influenza vaccination, for it may also have benefits for COVID-19 prevention.