Immunogenicity and safety of seasonal influenza vaccine co-administered with other vaccines: a systematic review and meta-analysis

Abstract

Abstract Seasonal influenza remains a leading cause of global morbidity and mortality, highlighting the need for vaccination strategies that improve coverage and streamline vaccine delivery. In this systematic review and meta-analysis, we searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Central Register of Controlled Trials for randomised controlled trials (RCTs), cohort, case-control, and cross-sectional studies, evaluating immunogenicity and safety of same-day co-administration of influenza vaccines with COVID-19 or other vaccines, compared with non-concomitant administration. Comparators included sequential administration, single vaccine administration or placebo-controlled delayed vaccination. Risk of bias was evaluated using the Cochrane Risk-of-Bias tool for Randomized Trials and Risk of Bias In Non-randomized Studies of Interventions; certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluation. Immunogenicity was assessed using geometric mean fold rise (GMFR) in antibody titres and seroprotection rate. Safety was assessed by adverse event (AE) incidence. 52 eligible studies were included. Influenza immunogenicity was comparable between the co-administration and non-concomitant comparator group across all strains (H1N1 GMFR ratio of means (ROM): 1.02 [95% CI: 0.95–1.10]; H3N2, 1.05 [95% CI: 0.97–1.13]; B strain, 1.01 [95% CI: 0.97–1.05]). Pooled risk ratio (RR) for seroprotection was 1.00 for all three strains with 95% CIs ranging from 0.99–1.01. GMFR for COVID-19 vaccines was modestly reduced under co-administration (ROM 0.84 [95% CI: 0.74–0.95]; p = 0.006). Serious AEs were more frequent in the co-administration group compared to the non-concomitant group (RR 1.41 [95% CI: 1.07–1.86]; p = 0.014; absolute risk difference: 1.56 percentage points). Overall, co-administration preserves influenza immunogenicity but modestly reduces COVID-19 vaccine GMFR. Although safety findings warrant cautious interpretation, the low absolute risk difference supports its feasibility as a strategy to streamline vaccination schedules and improve uptake.