Building on the evidence-to-recommendations of the 2023-2024 iteration of the Advisory Committee on Immunization Practices (ACIP), a systematic review and meta-analysis conducted by infectious disease specialists across the US brings forward evidence to inform 2025-2026 vaccination against COVID-19, RSV, and Influenza.1
"Recent changes to federal vaccine-advisory processes have disrupted immunization guidance, which underscores the need for independent evidence assessment," explains lead author Jake Scott, MD, Department of Medicine-Med/Infectious Diseases, Stanford University School of Medicine, Stanford, CA, and colleagues.
The review of evidence on vaccines was supported by the Vaccine Integrity Project of the Center for Infectious Disease Research and Policy (CIDRAP). The Project was launched by CIDRAP in April, which was formed in 2001 at the University of Minnesota. The news release announcing the Project indicated that the project, "will engage professionals across the US immunization landscape to gather feedback on how non-governmental entities may be able to help protect vaccine policy, information and utilization across the US."2
What You Need to Know
Evidence from more than 500 studies confirms that COVID-19, RSV, and influenza vaccines provide meaningful protection against hospitalization—often above 45–70% depending on the vaccine and population.
Serious adverse events such as myocarditis or Guillain-Barré syndrome were uncommon, and data showed no increased risks for adverse pregnancy outcomes; several vaccines even showed benefits like reduced preterm birth.
Studies show that giving COVID-19, influenza, and RSV vaccines together yields immunogenicity and safety comparable to spacing them out, supporting streamlined vaccination strategies for the 2025–2026 season.
The review was conducted by academic researchers and clinical experts over a 12-week period. It is intended, they indicate, "to provide clinicians, medical societies, public health professionals, insurers, and policymakers with timely evidence for the 2025-2026 respiratory virus season."
The investigators included randomized controlled trials (RCTs) and observational studies addressing four domains: US epidemiologic surveillance, laboratory-confirmed vaccine efficacy or effectiveness, safety, and vaccine co-administration.They culled 511 studies for inclusion from 1,406 that underwent full-text review; comprising RCTs (12%), cohort studies (24%), case-control series (16%), and other observational designs (48%).
Efficacy determinations included:
- COVID-19 mRNA vaccines against the XBB.1.5 subvariant had pooled vaccine effectiveness against hospitalization of 46% (CI, 34-55) from cohort studies and 50% (43-57) from case-control studies; with lower protection among immunocompromised adults.Vaccines against the KP.2 subvariant showed 68% (42-82) effectiveness in case-control studies
- Maternal RSV vaccination for infant protection, nirsevimab for infants, and RSV vaccines in adults ≥60 years of age showed effectiveness of at least 68%against hospitalization.
- Influenza vaccination had pooled vaccine effectiveness of 48% (39-55) in adults between 18-64 years of age and 67% (58-75) in children against hospitalization.
Safety findings included:
- Myocarditis associated with COVID-19 vaccines occurred at rates of 1.3-3.1 per 100,000 doses in male adolescents, with lower rates associated with longer dosing interval
- The RSVpreF vaccine was associated with 18.2 excess cases of Guillain-Barré syndrome per million doses in older adults.
- The RSVpreF was not associated with preterm birth when administered at 32 to 36 weeks' gestation.
- COVID-19 vaccination during pregnancy was not associated with miscarriage, congenital anomalies, or stillbirth, and was associated with lower risk of preterm birth in most studies.
Evidence on co-administration included:
- Co-administration of COVID-19 and influenza vaccines demonstrated similar immunogenicity and safety to sequential administration (17 studies); with similar results in adults ≥65 years of age (5 RCTs).
- Triple administration of COVID-19, RSV and influenza vaccine showed "acceptable immunogenicity and safety profiles".
The investigators found that evidence supports the safety and effectiveness of the immunizations for COVID-19, RSV, and influenza for the 2025-2026 season.
"Updated findings reaffirm that immunizations are associated with a substantial reduction in the risk of severe outcomes across populations, with only infrequent reports of key severe vaccine-related safety events, such as myocarditis and Guillain-Barré syndrome," Scott and colleagues report.
References
1. Scott J, Abers MS, Marwah HK, et al. Updated evidence for COVID-19, RSV, and Influenza vaccines for 2025-2026. N Engl J Med. Published online October 29, 2025. DOI:10.1056/NEJMsa2514268.
