How effective are 2025–2026 COVID-19 vaccines at preventing hospitalization and death by age group?
Executive summary
Real-world evidence from the 2024–2025 season—used to project likely performance of the 2025–2026 formulations—shows moderate protection against hospitalization and stronger protection against death or critical illness, with effectiveness highest in older adults for the most severe outcomes and lower but measurable benefits in younger groups; estimates cluster around ~40–50% effectiveness vs hospitalization and substantially higher (often >60%) vs death/IMV in many studies, though numbers vary by age, time since vaccination, and study population [1] [2] NEJMoa2510226" target="_blank" rel="noopener noreferrer">[3].
1. Overall adult protection: modest against hospitalization, robust against death
Network analyses (VISION and IVY) found 2024–2025 vaccines reduced COVID-19–associated hospitalizations by roughly 40–50% in adults during the analytic windows, while protection against invasive mechanical ventilation (IMV) or death was noticeably higher—studies reported VE ≈40% against hospitalization overall and up to ~79% against IMV or death in a multicenter IVY analysis [1] [4]. CDC VISION interim estimates reported VE of ~33% against ED/UC visits and ~45%–46% against hospitalization among immunocompetent adults ≥65 years, underscoring stronger benefit for severe outcomes than for milder illness [2] [5].
2. Older adults (≥65): best preserved protection for the worst outcomes
Multiple data streams converge on the pattern that vaccines give older adults the clearest protection against critical illness and death: IVY and VISION networks estimated ~45%–46% effectiveness against hospitalization in immunocompetent adults ≥65, while other cohort analyses (Veterans Affairs, NEJM) estimated VE against COVID-19–associated death as high as 64% at six months of follow-up [5] [2] [3]. Manufacturer and international data (Denmark) reported >60% protection against severe illness in older adults where JN.1-adapted vaccines were used, a higher point estimate that likely reflects differences in circulating variants, prior infection, and study design [6].
3. Younger adults and middle-aged groups: measurable but lower reductions in hospitalization
For adults 18–64, VE against hospitalization is lower than in seniors but still present: studies put the 7–119 day effectiveness against ED/UC encounters at ~30% in 18–64-year-olds and around ~33% overall, with hospitalization VE estimates in the 30%–46% range depending on immunocompetence and time since dose [5] [7] [3]. Protection wanes over weeks to months—reports show notable decline by 10 weeks for infection and more moderate declines for hospitalization or death—meaning timing of vaccination matters for peak protection [8] [9].
4. Children and adolescents: limited but favorable signals for severe outcomes
Pediatric data are thinner because of lower vaccine uptake and fewer severe outcomes, but large observational analyses indicate benefit: a UK OpenSAFELY analysis found vaccination in adolescents reduced COVID-19 hospitalization risk (incidence rate ratio ~0.58, roughly a 42% reduction) and other studies cited by ACIP and pediatric experts conclude vaccines prevent severe pediatric disease and deaths relative to influenza baseline risks [10] [11]. However, many U.S. networks could not estimate VE in children because of low baseline severe-disease rates and low coverage [12].
5. What to read into 2025–2026 expectations and uncertainties
Regulators recommended 2025–2026 monovalent JN.1-lineage/LP.8.1–preferred formulations because prior-season vaccines protected against JN.1 descendants and sustained protection through at least 90–179 days in some analyses, implying similar or improved performance for the 2025–2026 shots—but direct VE data for the new formulations are still limited and will depend on viral evolution, prior population immunity, and uptake [1] [9]. Independent reviews warn that VE percentages reflect added protection on top of widespread background immunity from prior infection/vaccination and that manufacturer communications (e.g., Danish data cited by Pfizer) can differ from U.S. network estimates because of design and population differences [13] [6].
6. Bottom line and caveats
The best synthesis of available reporting: expect roughly 30%–50% reduction in COVID-19 hospitalizations across adults (higher end in older adults and soon after vaccination) and substantially greater relative reductions against death or invasive ventilation (often >60% in cohort analyses), with waning, variant mix, prior infection, and study methods driving variability; uncertainties remain for children and for the exact performance of 2025–2026 formulations until post-licensure surveillance reports accumulate [1] [2] [3] [8].