Have other major studies found higher flu infection rates among vaccinated people?
Executive summary
Major surveillance networks found the 2024–25 U.S. interim flu vaccine effectiveness (VE) was low for some subtypes but did not report vaccinated people having higher overall infection rates; CDC networks published VE estimates using test‑negative designs and interim data [1] [2]. A large Cleveland Clinic preprint claimed a higher cumulative incidence among vaccinated employees and calculated a negative VE of −26.9% in that cohort [3] [4], but public health agencies’ multi‑site analyses and CDC summaries emphasize different methods, populations and outcomes [1] [2].
1. How major public‑health VE studies measured protection — and what they found
CDC’s four VE networks used the test‑negative design and multivariable logistic regression to estimate vaccine effectiveness against medically attended influenza, adjusting for region, age and calendar time; those interim analyses produced subtype‑specific VE estimates rather than simple vaccinated vs unvaccinated cumulative‑incidence comparisons [1] [2]. CDC’s public pages present numbers of vaccinated people with positive and negative tests and run adjusted models to produce VE, and they characterize results by virus subtype [2].
2. The Cleveland Clinic finding: a big sample, a surprising headline
A Cleveland Clinic analysis of 53,402 employees compared cumulative incidence over 25 weeks and reported that vaccinated working‑age adults had a higher risk of influenza this season, concluding they were “unable to find that the influenza vaccine has been effective” and reporting a calculated VE of −26.9% in the cohort [3] [4]. That result is a preprint on medRxiv (noted by Immunization Managers’ summary) and uses workplace‑employee surveillance and cumulative incidence as its primary measure [3] [4].
3. Why results can diverge: design, population and outcome differences
Test‑negative designs used by CDC networks estimate odds of vaccination among symptomatic people who test positive versus those who test negative and then adjust for confounders; that delivers an estimate of VE for medically attended illness, not raw cumulative incidence in an employed cohort [1] [2]. The Cleveland Clinic study measured cumulative infection rates among employees over time, a different outcome and a different population (working‑age adults in one health system), which can produce divergent results even in the same season [3].
4. The broader picture from surveillance and burden data
CDC surveillance reported record high hospitalizations and heavy seasonality in 2024–25 and continues to estimate disease burden, vaccination distribution and subtype mix for policy use; these systems showed heavy circulation of A(H1N1)pdm09 and A(H3N2) and emphasize reductions in severe outcomes as a key vaccine benefit [5] [6] [7]. Public summaries caution that interim VE estimates have limits and that final evaluations use multiple data streams [5] [2].
5. How experts and public‑facing sources framed the Cleveland Clinic result
Immunization Managers’ writeup highlighted that only about 2% of the Cleveland Clinic cohort had lab‑confirmed flu and cautioned against changing vaccination recommendations pending peer review; they reiterated that the ratio of positive tests was not significantly different between groups in some checks and urged awaiting peer‑reviewed publication [4]. Other outlets and analyses stress that vaccinated people often have milder disease and lower hospitalization risk — effects measured in different studies and not necessarily contradicted by the Cleveland Clinic cumulative‑incidence finding [8] [9].
6. Limitations, uncertainties and hidden drivers to watch
Different studies reflect different implicit agendas and constraints: public‑health networks aim to estimate population VE for policy using adjusted case‑control approaches, while institutional cohorts may focus on workplace risk and operational questions, and preprints haven’t been through peer review [1] [3] [4]. Surveillance and VE estimates are sensitive to timing of vaccination, prior immunity, circulating strain match, case ascertainment methods, health‑seeking behavior and adjustments for confounders — factors explicitly noted in CDC and journal reports [1] [2] [5].
7. Bottom line for readers and policymakers
Available major public‑health VE networks produced subtype‑specific, adjusted VE estimates rather than asserting vaccinated people had higher overall infection rates [1] [2]. One large institutional preprint reported higher cumulative incidence among vaccinated employees and a negative VE estimate, but it differs in design, population and peer‑review status from CDC network analyses and has prompted calls for cautious interpretation until reviewed [3] [4]. Available sources do not mention definitive proof that vaccination increases flu infection risk across general populations (not found in current reporting).