A Systematic Review and Meta-Analysis on the Effectiveness of Bivalent mRNA Booster Vaccines against Omicron Variants

Abstract

ABSTRACTBackgroundA global shift to bivalent mRNA vaccines is ongoing to counterbalance diminishing monovalent vaccine effectiveness (VE) due to the evolution of SARS-CoV-2 variants, yet substantial variation in the bivalent VE exists across studies and a complete picture is lacking.MethodsWe searched papers evaluating SARS-CoV-2 bivalent mRNA vaccines on PubMed, Web of Science, Cochrane Library, Google Scholar, Embase, Scopus, bioRxiv, and medRxiv published from September 1st, 2022, to November 8th, 2023. Pooled VE against Omicron-associated infection and severe events was estimated in reference to unvaccinated, ≥2 monovalent doses, and ≥3 monovalent doses.ResultsFrom 630 citations identified, 28 studies were included, involving 55,393,303 individuals. Bivalent boosters demonstrated superior protection against symptomatic or any infection compared to unvaccinated, ≥2 monovalent doses, and ≥3 monovalent doses, with corresponding relative VE estimated as 53.5% (95% CI: - 22.2-82.3%), 30.8% (95% CI: 22.5-38.2%), and 28.4% (95% CI: 10.2-42.9%) for all ages, and 22.5% (95% CI: 16.8-39.8%), 31.4% (95% CI: 27.7-35.0%), and 30.6% (95% CI: -13.2-57.5%) for adults ≥60 years old. Pooled bivalent VE estimates against severe events were higher, 72.9% (95% CI: 60.5-82.4%), 57.6% (95% CI: 42.4-68.8%), and 62.1% (95% CI: 54.6-68.3%) for all ages, and 72.0% (95% CI: 51.4-83.9%), 63.4% (95% CI: 41.0-77.3%), and 60.7% (95% CI: 52.4-67.6%) for adults ≥60 years old, compared to unvaccinated, ≥2 monovalent doses, and ≥3 monovalent doses, respectively.ConclusionsBivalent boosters demonstrated higher VE against severe outcomes than monovalent boosters across age groups, highlighting the critical need for improving vaccine coverage, especially among the vulnerable older subpopulation.