What are real-world effectiveness estimates for 2025 flu vaccines by age group and comorbidity status?
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Executive summary
Interim U.S. estimates for the 2024–25 influenza season show vaccination reduced medically attended flu and hospitalizations across age groups, with CDC reporting that vaccination was effective in children, adolescents and adults [1]. Large Southern Hemisphere 2025 surveillance found vaccines cut outpatient visits and hospitalizations by about half (≈50.4% and 49.7%) and reported subgroup VEs in children, people with comorbidities and older adults [2]. A single large employer preprint reported an unexpected negative VE in working‑age adults (−26.9%), a result that public health groups caution should not by itself change recommendations [3] [4].
1. What the major U.S. networks reported: interim, age‑stratified protection
Four U.S. VE networks (U.S. Flu VE, IVY, NVSN, VISION) published interim 2024–25 estimates showing the seasonal vaccine “was effective in preventing medically attended influenza‑associated illness in children, adolescents, and adults” and reduced influenza‑associated hospitalization; these estimates come from test‑negative designs combining outpatient and hospitalization surveillance October 2024–February 2025 [1] [5]. The CDC page assembling preliminary VE tables for the 2024–25 season provides age group breakdowns and network‑level results; those tables are the primary source for U.S. midseason VE numbers [6].
2. Southern Hemisphere data: ~50% protection overall, subgroup signals
An international pooled analysis from eight Southern Hemisphere countries during their 2025 season estimated vaccines reduced influenza‑associated outpatient visits by roughly 50.4% and hospitalizations by 49.7% [2]. That report supplied subgroup VE: about 51.3% against hospitalization in young children, 51.9% among people with underlying conditions (priority groups), and lower VE in older adults (around 37.7% depending on age cutoffs) — demonstrating protection varies by age and comorbidity status [7] [2].
3. A contradictory single‑site preprint and how authorities reacted
A Cleveland Clinic employee cohort preprint covering 53,402 working‑age adults reported a higher risk of influenza among the vaccinated state, yielding a calculated VE of −26.9% (95% CI, −55.0 to −6.6%) in adjusted Cox models [3]. Public health and immunization managers flagged that the study is a single‑employer, preprint analysis with limitations and advised it should not change vaccination recommendations pending peer review and broader corroboration [4].
4. Why VE numbers differ: design, outcome, timing, and circulating strains
VE estimates differ across studies because networks use different settings (outpatient vs. hospitalized), age definitions, analytic adjustments, and timing of measurement — and because influenza viruses evolve during and after vaccine strain selection [6] [1] [8]. Southern Hemisphere results can be an early indicator for the Northern Hemisphere, but transferability depends on whether the same viruses circulate later [2].
5. The big determinant now: strain match and emerging variants
Multiple reports flagged that vaccine composition and emerging H3N2 variants (including a subclade labelled K) may alter real‑world protection: early data and commentary show cases where mismatch reduced lab reactivity, though some early post‑vaccination analyses in children showed strong protection against hospital attendance (70–75%) while adult protection estimates were lower (30–40%) in some early Northern Hemisphere assessments [9]. The FDA and WHO strain‑selection documents note vaccine composition decisions depend on circulating strain data and midseason VE monitoring [8].
6. Practical read: by age and comorbidity what to expect now
Available U.S. and international reporting for the 2024–25 and Southern Hemisphere 2025 seasons indicates moderate vaccine effectiveness overall (around one‑half reduction in medically attended illness and hospitalization in pooled Southern Hemisphere data) and higher relative impact in children and people with underlying conditions than in older adults [2] [1]. Precise age‑by‑comorbidity VE estimates for the 2025–26 Northern Hemisphere season are still evolving in the reporting; CDC’s interim U.S. tables give the most granular current breakdowns [6] [5].
7. Limitations, uncertainty and competing interpretations
Key limitations: interim estimates can change by season’s end, single‑site preprints can show divergent results that may reflect biases (occupational exposure, behavior, prior immunity), and strain evolution after vaccine selection creates uncertainty about future protection [3] [4] [8]. Public health agencies continue to recommend annual vaccination for everyone ≥6 months old while acknowledging VE varies; they and external investigators present competing signals—broad networks showing benefit [1] [5] versus a single employer preprint suggesting no protection in a specific adult cohort [3].
8. Bottom line for clinicians and people making decisions
Current multi‑country and multi‑network surveillance indicates the 2024–25/2025 vaccines provided meaningful protection—about 40–50% reduction in medically attended illness and hospitalization in pooled analyses and stronger relative protection in children and persons with comorbidities—while at least one large preprint raised questions in a particular working‑age cohort that public health bodies say does not alone warrant changing vaccination policy [2] [1] [3] [4]. For exact, age‑ and comorbidity‑stratified point estimates consult the CDC interim tables and the Southern Hemisphere MMWR report cited above [6] [2] [5].