Abstract

Background: Despite the success of mRNA vaccines, COVID-19 remains a significant public health threat. Waning of immune memory and the emergence of new variants can degrade population-level protection and contribute to ongoing morbidity. Method(s): In this systematic review and meta-regression, we searched for studies in PubMed, medRxiv and bioRxiv published January 1, 2020 - January 1, 2023 measuring vaccine effectiveness as the reduction in infection, symptomatic disease, and severe disease (resulting in hospitalization and/or death) conferred by mRNA-based vaccination and prior SARS-CoV-2 infections relative to naive individuals. We excluded studies that did not distinguish between mRNA and non-mRNA vaccines or had less than 1000 participants. Using a multi-level model, we quantified the initial effectiveness and change over four to six months following vaccination or infection. Model covariates were COVID variant, number of vaccine doses, and the number and variant of prior infection. Our estimates were adjusted for the age of the study population. Finding(s): Of 828 screened, we included 123 studies in our analysis. Vaccine effectiveness against infection and disease declined both over time and with the emergence of Omicron, regardless of booster doses, though protection against severe outcomes was more durable. Booster doses reduced severe Omicron infections by 90.5 % (95 % confidence interval 87.1-93.8) and 77.6 % (70.5-84.7) at two and 26 weeks post-vaccination, respectively. Protection conferred by hybrid immunity was more durable than that from either vaccination or prior infection alone, but protection against Omicron reinfection was only 50.1 % (32.5-67.8) at 26 weeks following vaccination. Individuals with hybrid immunity had 80.6 % protection (70.0-91.2) following booster doses declining to 36.9 % (19.3-54.6) after 16 weeks. Interpretation(s): Our results suggest that timely deployment of pre-existing boosters can greatly mitigate seasonal COVID outbreaks even in populations with prior infection and vaccination. Funding(s): Centers for Disease Control and Prevention (NU38OT000297-03). Copyright © 2025

All age groups COVID-19 Efficacy/effectiveness Administration