Real-World Effectiveness of RSVpreF and RSVpreF3 Vaccines in Preventing Hospitalization and Emergency Department Visits Associated With Respiratory Syncytial Virus in Older Adults: A Meta-analysis

Abstract

Background: Respiratory syncytial virus (RSV) vaccines were first recommended for older adults during the 2023–2024 season in countries that authorized their use. Although early observational studies complemented trial findings, real-world evidence on vaccine effectiveness against severe RSV disease remains limited. We assessed the effectiveness of RSVpreF and RSVpreF3 vaccines in preventing RSV-related hospitalizations and emergency department (ED) visits among older adults. Methods: We searched MEDLINE, Embase, Web of Science, Scopus, Global Health, and medRxiv for observational studies published between 1 January 2023 and 30 December 2025, reporting real-world effectiveness of RSV vaccines in adults aged 60 years or older. Pooled analyses used inverse-variance random-effects models to estimate effectiveness against RSV-related hospitalizations and ED visits. Subgroup analyses assessed differences in effectiveness by age, immune status, and vaccine type. This study is registered with PROSPERO (CRD420251021777). Results: From 4925 records screened, 8 cohort and case-control studies were included. Vaccination was associated with lower odds of RSV-related hospitalization (odds ratio [OR]: 0.23; 95% confidence interval [CI], 0.20–0.27; I² = 6.5%) and ED visits (OR: 0.23; 95% CI, 0.21–0.27; I² = 0.0%). Effectiveness against RSV-related hospitalization was lower in immunocompromised adults (OR: 0.31; 95% CI, 0.27–0.34; I² = 0.0%) than in immunocompetent individuals (OR: 0.20; 95% CI, 0.11–0.35; I² = 0.0%). Effectiveness did not differ by age group (60–74 vs ≥75 years) or vaccine product. Conclusions: Vaccination provided substantial protection against RSV-related healthcare utilization among older adults. Continued surveillance and real-world evidence are needed to inform immunization policy and improve protection in immunocompromised individuals.