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 SARSCoV-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-19associated hospitalization (SRR 0.90, 95% CI 0.68-1.19), or COVID-19-related mortality (SRR 0.83, 95% CI 0.561.23). 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. (c) 2024 The Author(s). Published by Elsevier Inc. on behalf of Association for Professionals in Infection Control and Epidemiology, Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).