What are end‑of‑season, peer‑reviewed vaccine effectiveness estimates for 2025–26 by age and outcome (infection, medical attendance, hospitalization)?
Executive summary
Peer‑reviewed, end‑of‑season estimates specifically labeled “2025–26 end‑of‑season” remain limited in the literature, but a systematic NEJM review of studies through July 31, 2025 concluded that ongoing peer‑reviewed evidence supports the safety and effectiveness of COVID‑19, RSV, and influenza immunizations for the 2025–2026 season [1] [2]. Available peer‑reviewed network and surveillance analyses provide outcome‑specific ranges: for COVID‑19, most robust published estimates through 2024–25 show meaningful protection against hospitalization though effectiveness against infection wanes; for influenza, Southern Hemisphere and multi‑jurisdictional interim analyses point to substantial reductions in severe outcomes (often 30–75% depending on age); for RSV, peer‑reviewed pooled estimates especially in high‑risk groups show strong protection against hospitalization [3] [4] [5] [6].
1. COVID‑19: hospitalization protection strongest, infection protection variable
Peer‑reviewed hospital surveillance and test‑negative case‑control networks (IVY, VISION) show vaccines for the 2024–25/updated formulations reduced COVID‑19–associated hospitalization—VE estimates vary by age, time since vaccination, immunocompromise and circulating lineage and are reported using (1 − adjusted odds ratio) × 100% methods [3] [7]. The NEJM systematic review that captured studies through July 31, 2025 summarized that evidence supports effectiveness against severe outcomes, while public GRADE assessments noted low to very low certainty for some age/harm endpoints but consistently prioritized prevention of severe disease [1] [8]. Manufacturer summaries cite ranges (e.g., Pfizer 2024–25 KP.2 study reporting ~41–75% effectiveness against hospitalization and >56% against outpatient/ED visits in adults) but those are company data and should be interpreted alongside independent network analyses [9] [3].
2. Influenza: mid‑season and Southern Hemisphere signals point to 30–75% protection against severe outcomes
Interim, peer‑reviewed and public health surveillance from the 2025 Southern Hemisphere season—used to anticipate Northern Hemisphere 2025–26 performance—show vaccine effectiveness against medically attended illness and hospitalization that in many settings translated to 30–75% reductions in severe outcomes depending on age and dominant strain; CDC and MMWR published multi‑country analyses of outpatient and SARI surveillance underpinning those estimates [4] [5] [10]. The NEJM review included influenza observational effectiveness studies up to July 2025 and concluded ongoing evidence supports influenza vaccine effectiveness for the coming season, while noting variability by age and match between vaccine and circulating clades [1] [2].
3. RSV: strong hospitalization benefit in high‑risk and older adults, evidence growing
Peer‑reviewed pooled estimates and guidelines for immunocompromised and older adults report substantial VE against RSV‑associated hospitalization—IDSA cites a pooled estimate near 70% (95% CI 66–73%) in immunocompromised patients and single studies showing up to ~81% against critical illness in older adults [6]. NEJM’s systematic review included randomized and observational RSV vaccine studies through the search window and concluded evidence supports RSV vaccine effectiveness for the 2025–26 season, though estimates vary by population and endpoint [1] [2].
4. Cross‑cutting caveats: timing, study designs, and vested sources matter
End‑of‑season peer‑reviewed synthesis for 2025–26 is still consolidating: the NEJM review used studies through July 2025 and CIDRAP’s published meta‑analysis and interactive VIP toolkit summarized a “sea of data” for fall 2025 but also underscored heterogeneity in study designs, endpoints, and follow‑up windows [1] [11]. Interim manufacturer statements (e.g., Pfizer) report promising ranges but are not a substitute for independent, peer‑reviewed network analyses [9] [3]. Influenza VE is highly contingent on antigenic match and age, COVID‑19 VE wanes with time and variant immune escape, and RSV VE estimates are strongest for hospitalization prevention in older or immunocompromised patients [4] [3] [6].
5. Bottom line: reliable ranges and what’s still unknown
Peer‑reviewed, network and surveillance data available to mid‑2025 support these pragmatic, outcome‑specific ranges for 2025–26 planning: COVID‑19 vaccines—substantial reduction in hospitalization (VE often in the tens of percent to higher ranges depending on subgroup and recency of vaccination) though lower and more variable for infection and outpatient visits [3] [7]; influenza vaccines—commonly 30–75% reduction in severe outcomes by age in recent surveillance with larger variation for preventing any infection [4] [5]; RSV vaccines—strong protection against hospitalization in older/immunocompromised adults with pooled VE ~70% in some analyses [6]. Final, peer‑reviewed “end‑of‑season 2025–26” pooled estimates will require full Northern Hemisphere season data and meta‑analysis beyond July 2025; current best evidence nonetheless supports vaccination to reduce medical attendance and hospitalization across these respiratory viruses [2] [1] [11].