Influenza vaccination and COVID-19 infection risk and disease severity: A systematic review and multilevel meta-analysis of prospective studies

Background: In light of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, the influence of influenza vaccination on the risk and severity of Coronavirus Disease 19 (COVID-19) has been a subject of debate. This systematic review and meta-analysis of prospective studies aim to assess the association between influenza immunization and the risk of SARS-CoV-2 infection and subsequent COVID-19 disease severity. Methods: A comprehensive search of PubMed and Embase databases was performed to identify prospective studies published before March 2024. We focused on evaluating the effect of influenza vaccination on SARS-CoV-2 infection risk and severe COVID-19 outcomes, such as hospitalization and mortality. The analysis employed a multilevel random effects meta-analysis approach. The risk of bias assessment was conducted using the Newcastle-Ottawa Scale. Results: From an initial pool of 5,863 records, 14 studies were selected for inclusion. The aggregated data yielded a summary relative risk (SRR) that showed no significant protective correlation between influenza vaccination and SARS-CoV-2 infection risk (SRR 0.95, 95% confidence interval [CI] 0.81-1.11), COVID-19-associated hospitalization (SRR 0.90, 95% CI 0.68-1.19), or COVID-19-related mortality (SRR 0.83, 95% CI 0.56-1.23). Conclusions: This systematic review and meta-analysis, based exclusively on prospective studies, demonstrates the lack of a proven protective effect of influenza vaccination against COVID-19 and related outcomes. Our results do not support a significant protective effect of influenza vaccination against the risk or severe outcomes of COVID-19.