Updated Evidence for Covid-19, RSV, and Influenza Vaccines for 2025-2026

Changes in the vaccine advisory process in the United States have disrupted immunization guidance, which reinforces the need for independent evidence review to inform decisions regarding immunization for respiratory viruses during the 2025-2026 season.

We conducted a systematic review of U.S.-licensed immunizations against coronavirus disease 2019 (Covid-19), respiratory syncytial virus (RSV), and influenza. We searched databases on PubMed/MEDLINE, Embase, and Web of Science for updates of the most recent review by the Advisory Committee on Immunization Practices (ACIP) Evidence-to-Recommendations for each disease, which was performed during the 2023-2024 period. Outcomes included vaccine efficacy and effectiveness against hospitalization, other clinical end points, and safety.

Of 17,263 identified references, 511 studies met the inclusion criteria. Covid-19 mRNA vaccines against the XBB.1.5 subvariant had pooled vaccine effectiveness against hospitalization of 46% (95% confidence interval [CI], 34 to 55; from cohort studies) and 50% (95% CI, 43 to 57; from case-control studies) among adults and 37% (95% CI, 29 to 44) among immunocompromised adults. In a case-control study, vaccines against the KP.2 subvariant showed an effectiveness of 68% (95% CI, 42 to 82). Maternal RSV vaccination (for infant protection), nirsevimab for infants, and RSV vaccines in adults who were 60 years of age or older showed vaccine effectiveness of 68% or more against hospitalization. Influenza vaccination had a pooled vaccine effectiveness of 48% (95% CI, 39 to 55) in adults between the ages of 18 and 64 years and 67% (95% CI, 58 to 75) in children against hospitalization. Safety profiles were consistent with previous evaluations. The diagnosis of myocarditis associated with Covid-19 vaccines occurred at rates of 1.3 to 3.1 per 100,000 doses in male adolescents, with lower risk associated with longer dosing intervals. The RSVpreF vaccine was associated with 18.2 excess cases of Guillain-Barré syndrome per million doses in older adults; a significant association with preterm birth was not observed when the vaccine was administered at 32 to 36 weeks' gestation.

Ongoing peer-reviewed evidence supports the safety and effectiveness of immunizations against Covid-19, RSV, and influenza during the 2025-2026 season. (Funded by the Center for Infectious Disease Research and Policy and the Alumbra Innovations Foundation.).