Highlights
- Real-world vaccine effectiveness (VE) against RSV-associated hospitalization and severe disease in adults aged 60 and older remains high, ranging from 74.8% to 79.8%.
- Global vaccine uptake is notably low, with the United States reporting only 18.0% coverage during the 2023/24 season, highlighting significant disparities across sociodemographic groups.
- Post-licensure surveillance identified a rare safety signal for Guillain-Barré syndrome (GBS), with incidence rates slightly higher for the RSVpreF vaccine compared to the RSVPreF3+AS01 formulation.
- The benefit-risk profile strongly supports continued and expanded RSV vaccination programs to mitigate the substantial burden of lower respiratory tract disease in aging populations.
Background: The Evolving Burden of RSV in Aging Populations
For decades, Respiratory Syncytial Virus (RSV) was primarily viewed through the lens of pediatric medicine. However, emerging epidemiological data have reframed RSV as a significant pathogen in older adults, often rivaling influenza in terms of morbidity and mortality among the elderly and those with underlying cardiopulmonary conditions. The pathophysiology of RSV in older adults is complicated by immunosenescence—the gradual decline in immune function associated with aging—which increases susceptibility to lower respiratory tract disease (LRTD), pneumonia, and exacerbations of chronic obstructive pulmonary disease (COPD) or heart failure.
The recent licensure and rollout of several RSV vaccines, including the protein subunit vaccines RSVPreF3+AS01 (Arexvy, GSK) and RSVpreF (Abrysvo, Pfizer), represent a landmark achievement in preventative geriatrics. While Phase 3 clinical trials demonstrated high efficacy, real-world evidence (RWE) is essential to validate these findings across diverse populations, assess the duration of protection, and identify rare adverse events that may not surface in smaller trial cohorts. This systematic review and meta-analysis provides the most comprehensive evaluation to date of how these vaccines are performing in clinical practice.
Study Design and Methodology
This study, published in The Lancet Regional Health – Europe, utilized a rigorous systematic review and meta-analysis framework. The researchers conducted 11 monthly longitudinal searches between November 2024 and November 2025 across major databases, including Ovid Medline, Embase, and Global Health. The study was registered with PROSPERO (CRD42025643585).
From an initial pool of 3,900 identified studies, 36 were selected for inclusion based on their focus on post-licensure real-world data. These studies covered a massive population of over 121.8 million individuals across nine countries: the United States, United Kingdom, Italy, Australia, Czech Republic, Switzerland, France, Canada, and Israel. The researchers employed random-effects modelling to pool estimates for three primary domains: vaccine uptake, vaccine effectiveness (VE), and safety signals.
Key Findings: Vaccine Uptake and Sociodemographic Disparities
One of the most striking findings of the meta-analysis was the relatively low uptake of the RSV vaccine globally. In the United States, which had the most robust data for the 2023/24 RSV season, the pooled uptake among adults aged 60 and older was only 18.0% (95% CI: 12.2-25.7). This suggests that despite the availability of effective prevention, a vast majority of the target population remains unvaccinated.
Subgroup Variations
The data revealed significant disparities in uptake based on clinical and sociodemographic factors. Individuals with pre-existing chronic conditions and those in older age brackets (e.g., 75+) tended to have slightly higher uptake rates, likely reflecting targeted clinical recommendations. However, disparities persisted across ethnic and socioeconomic lines, suggesting that barriers to access, vaccine hesitancy, or gaps in provider communication continue to hinder the reach of immunization programs.
Real-World Effectiveness: Robust Protection Against Severe Disease
While uptake was low, the effectiveness of the vaccines in those who received them was remarkably consistent with, and in some cases exceeded, clinical trial expectations. The meta-analysis pooled data across several key clinical endpoints for adults aged 60 and older:
- Laboratory-Confirmed RSV Infection: The pooled VE was 75.3% (95% CI: 73.7-76.9), based on three studies.
- Emergency Department (ED) and Urgent Care Visits: The vaccines provided 76.4% protection (95% CI: 74.2-78.5) against RSV-related outpatient acute care, based on four studies.
- Hospital Admissions: A critical metric for healthcare systems, the VE against RSV-related hospitalization was 74.8% (95% CI: 66.8-82.9), based on six studies.
- Severe RSV-Associated Disease: The highest level of protection was observed against severe disease (defined by oxygen requirement or ICU admission), with a pooled VE of 79.8% (95% CI: 68.1-91.5).
These findings underscore the clinical value of RSV vaccination in preventing the most resource-intensive and life-threatening complications of the virus.
Safety Profile: Analyzing the Guillain-Barré Syndrome Signal
Safety is a paramount concern for any new vaccine platform. The systematic review identified a rare but statistically significant safety signal regarding Guillain-Barré syndrome (GBS), a neurological condition where the body’s immune system attacks the nerves. The meta-analysis quantified this risk across the two primary vaccine formulations:
RSVPreF3+AS01 (Arexvy)
Two studies reported GBS incidence following the administration of the adjuvanted RSVPreF3 vaccine. The estimated rate was between 5.2 and 6.5 cases per one million doses administered.
RSVpreF (Abrysvo)
The non-adjuvanted bivalent RSVpreF vaccine showed a slightly higher reported incidence, ranging between 9.0 and 18.2 cases per one million doses.
While these figures represent an increase over the background rate of GBS in the general elderly population, they remain extremely rare. For clinicians, the challenge lies in balancing this minimal risk against the much higher probability of severe respiratory complications and death from RSV infection.
Expert Commentary: Clinical and Policy Implications
The findings of this meta-analysis provide a clear mandate for healthcare providers and public health officials. The high effectiveness against hospitalization (74.8%) and severe disease (79.8%) suggests that increasing vaccine coverage could significantly alleviate the seasonal strain on hospital systems.
Addressing the GBS Signal
Medical experts emphasize that the GBS signal, while requiring continued monitoring, should be viewed in context. The number of hospitalizations and deaths prevented by the vaccine far outweighs the rare instances of GBS. However, the slightly higher rate observed with the RSVpreF formulation may influence clinical decision-making for patients with a history of GBS or specific neurological vulnerabilities.
The Need for Improved Uptake
The 18% uptake rate in the US is a call to action. Research suggests that a strong recommendation from a healthcare provider is the single most important factor in patient vaccine acceptance. Strategies must also address the “vaccine fatigue” observed post-COVID-19 and ensure that RSV vaccination is integrated into routine geriatric care alongside influenza and pneumococcal immunizations.
Conclusion: The Path Forward
This systematic review and meta-analysis by Trusinska et al. confirms that RSV vaccines are a potent tool in the geriatric armamentarium. They offer robust, high-level protection against severe respiratory outcomes in the real world. While the identification of a rare GBS signal is an important outcome of post-licensure surveillance, the overall safety profile remains favorable given the high disease burden of RSV.
Future research should focus on the multi-season durability of these vaccines and the effectiveness of revaccination strategies. For now, the priority remains clear: improving equitable access and increasing uptake to ensure that the clinical benefits of these vaccines reach the millions of older adults at risk.
Funding and Registration
This study received no specific funding. The protocol was prospectively registered with PROSPERO under registration number CRD42025643585.
References
Trusinska D, Lee B, Ferdous S, Lansbury L, Burden C, Anand A, Stowe J, Mensah A, Lim W, Marsh K, Gibbons C, Shi T. Real-world evidence on RSV vaccine uptake, effectiveness, and safety in older adults: a systematic review and meta-analysis. Lancet Reg Health Eur. 2026 Feb 20;64:101623. doi: 10.1016/j.lanepe.2026.101623. PMID: 41767892; PMCID: PMC12936786.
