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

Abstract

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.

Changes in Attitudes and Beliefs Concerning Vaccination and Influenza Vaccines between the First and Second COVID-19 Pandemic Waves: A Longitudinal Study

“…Moreover, by exerting the so-called "trained immunity" effect (i.e., by boosting the innate immune system), IV may reduce the incidence of some COVID-19-related outcomes. A systematic review and meta-analysis by Wang et al [48] recently demonstrated a 14% (aOR 0.86, 95% CI: 0.81-0.91) reduction in the odds of being positive to SARS-CoV-2 in subjects vaccinated against influenza, as compared with non-vaccinated subjects. This argument could also be used to increase IV acceptance.…”

Co-Ordination of Mucosal B Cell and CD8 T Cell Memory by Tissue-Resident CD4 Helper T Cells

“…Vaccination still remains the best approach to mitigate disease burden caused by respiratory viral infection. Current vaccines against influenza and SARS-CoV2 infections are mainly administered via the systemic route, which induces strong systemic but typically weak mucosal immune responses [ 141 , 142 , 143 , 144 ].…”

A new call for influenza and pneumococcal vaccinations during COVID-19 pandemic in Italy: A SIP/IRS (Italian Respiratory Society) and SITA (Italian Society of Antiinfective therapy) statement

“…Although preventable, both seasonal influenza and pneumococcal diseases still cause a significant amount of severe cases and death each year [ 6 , 7 , 8 , 9 ].…”

“…Seasonal influenza epidemics implies a well-documented burden on healthcare systems during winter time and result in considerable mortality with estimates of 250,000 – 500,000 death annually [ 5 ]. Older age and comorbidities accounted as the most common risk factors for influenza-related complications including mortality [ 6 , 7 ].…”

“…Second, in the light of a possible resurgence of influenza infection in the next winter season, a proactive approach to immunization can reduce influenza and pneumococcal related medical visits and Emergency Room admissions, thus alleviating the burden for healthcare systems, sparing medical resources and enabling better COVID-19 diagnosis and surveillance [ 6 , 20 ]. Recent studies revealed that influenza and pneumococcal immunizations had a significant implication in mitigating both COVID-19 infection and clinical outcomes [ 21 , 22 , 23 ].…”