Which age groups (children, adults 18–64, 65+) saw the largest reduction in severe flu outcomes from 2025–2026 vaccines?
Executive summary
Interim U.S. data for the 2024–25/2025 seasons show the largest measured reductions in severe outcomes (hospitalization) were among children and adolescents, where vaccination was associated with reductions up to about 78% in some interim reports, while older adults showed smaller or more variable protection in some datasets (for example, pooled estimates in separate vaccine reviews show ~37–56% in older adults for related vaccines) [1] [2]. International Southern Hemisphere 2025 surveillance suggests vaccines cut hospitalizations roughly in half overall, with higher point estimates in young children (~51%) and lower estimates in older adults (~37.7%) [3] [4].
1. What the U.S. interim networks reported — children saw the biggest drops
Interim estimates from four U.S. vaccine-effectiveness networks published by CDC and collaborators concluded that the 2024–25 influenza vaccination was effective in preventing medically attended illness and that vaccination was associated with large reductions in flu-associated hospitalization in children and adolescents — the Medical Letter and CDC interim reports note reductions “up to 78%” in risk of influenza-associated hospitalization in children and adolescents in U.S. data [1] [5]. Those network reports are the most direct U.S. evidence pointing to children as the age group with the largest measurable reduction in severe flu outcomes in the available reporting [5] [1].
2. Older adults: protection exists but is smaller and more variable in these reports
Available sources show older adults received measurable but generally smaller reductions in severe outcomes compared with children. A pooled analysis of studies of updated vaccines cited in NEJM and related reviews reported vaccine effectiveness against hospitalization among adults ≥65 ranging from about 41% to 56% in some cohorts, while other combined-study estimates were lower [2]. Southern Hemisphere surveillance also estimated lower VE against hospitalization in older adults (~37.7%) compared with children (~51.3%) [3] [4]. In short, older adults benefit, but point estimates are lower and more variable than those reported for children [3] [2].
3. Working‑aged adults (18–64): mixed signals and study-level variation
Results for adults 18–64 are mixed across datasets. Some large U.S. observational studies and interim network analyses reported moderate protection against outpatient illness and hospitalization in adults, but other single‑site analyses produced surprising or negative VE estimates. For example, a Cleveland Clinic employee cohort reported an apparent increased risk of laboratory‑confirmed influenza among vaccinated working‑age employees for 2024–25 (a calculated VE of −26.9%), though that was a single institutional study and has been highlighted and critiqued in subsequent commentary [6] [7]. Broader surveillance networks and multi‑site analyses used by CDC generally reported effectiveness in adults and did not replicate that negative VE signal across national datasets [5] [8].
4. International Southern Hemisphere data — about a 50% reduction overall, children outperform older adults
Interim analyses from eight Southern Hemisphere countries for 2025 found the seasonal vaccine reduced influenza-associated outpatient visits by ~50.4% and hospitalizations by ~49.7% overall; within subgroups, VE against hospitalization was ~51.3% for young children and ~37.7% for older adults (age cutoffs vary by country) [4] [3]. Authors and CDC noted that Northern Hemisphere 2025–26 vaccine composition matched the Southern Hemisphere composition, implying similar performance if circulating strains align [4].
5. Why age differences appear — biological reasons and surveillance artifacts
Sources emphasize two consistent themes: children often show higher vaccine effectiveness against hospitalization than older adults, and older adults experience faster waning and generally lower immune responses to standard vaccines [9] [2]. Surveillance differences, case definitions, and vaccine types (high‑dose, adjuvanted, recombinant) also matter — ACIP preferential recommendations for older adults reflect attempts to boost protection in that group [1] [2]. Additionally, single‑site studies can be biased by testing behavior and population differences, which helps explain divergent findings such as the Cleveland Clinic result [6] [7].
6. Limitations, disagreements, and what’s not in these sources
Available sources do not present a single definitive head‑to‑head age‑group comparison for the 2025–26 vaccine season across all U.S. populations; instead they offer interim, network, and international estimates that point to children having the largest reductions in severe outcomes and older adults showing smaller, variable protection [5] [4] [1]. The Cleveland Clinic negative-VE finding concerns working‑age adults but is a single institution’s analysis and is at odds with multi‑site network data; critiques and context about testing differences are available in commentary [6] [7]. Sources do not provide a pooled, final 2025–26 age-stratified hospitalization reduction that would replace interim and region‑specific estimates (not found in current reporting).
Bottom line: interim multi‑site and international surveillance consistently show the biggest vaccine-attributed reductions in severe flu outcomes in children and adolescents, smaller and more variable reductions in adults ≥65, and mixed signals for working‑age adults depending on the study — use multi‑site network and international estimates for the most reliable age comparisons [5] [4] [1].