A large-scale prospective cohort study from the Cleveland Clinic has delivered a shocking verdict on this year’s influenza vaccine: not only was it ineffective, but it was also associated with increased risk of infection. Led by Dr. Nabin Shrestha, the study tracked over 53,000 employees during the 2024–2025 respiratory viral season to assess whether the influenza vaccine offered protection against laboratory-confirmed influenza infections. The results raise serious questions about this season’s flu vaccine and the broader assumptions behind annual mandates. Hypothesis, Study Design & Methods
The study aimed to evaluate the real-world effectiveness of the 2024– 2025 influenza vaccine among relatively healthy, working-aged adults in a healthcare setting. All employees of Cleveland Clinic’s Ohio facilities as of October 1, 2024—the start of vaccine rollout—were included. Vaccination status was treated as a time- dependent covariate, allowing rigorous tracking of influenza incidence over a 25-week period. Cox proportional hazards models, adjusted for age, sex, job type, and location, were used to calculate risk. The primary endpoint: time to confirmed influenza infection (via nucleic acid amplification testing for influenza A or B).
Vaccinated at Higher Risk of Flu
Of the 53,402 employees analyzed, 82.1% received the flu vaccine. Yet, the cumulative incidence of influenza climbed faster in the vaccinated than the unvaccinated cohort. A total of 1,079 infections occurred—overwhelmingly, influenza A. After multivariable adjustment, the vaccinated had a 27% higher risk of influenza infection (HR 1.27, 95% CI: 1.07–1.51, P = 0.007), translating to a vaccine effectiveness of –26.9%. These results are not due to testing bias: while vaccinated individuals were more likely to get tested, their test positivity rate was nearly identical to the unvaccinated, indicating a true excess of infections.
Red Flags in the Data
The findings are deeply concerning. The negative vaccine effectiveness (VE) figure—suggesting harm rather than protection—contradicts public health messaging and raises serious questions about strain mismatch, immune interference, or potential vaccine-related susceptibility. This was not a marginal statistical fluke. The signal held in both unadjusted and adjusted models and was detected early using time-dependent methods. No protective effect emerged at any point.
Moreover, this wasn’t a flawed population. The cohort skewed young (mean age 42), mostly healthy, with high occupational compliance. The data were robust enough to reject the common defense that odds ratios from “test-negative” studies exaggerate protection—because here, direct risk was measured.
Study Limitations
The study focused on the inactivated trivalent vaccine, used by 99% of participants. Effectiveness of other formulations like quadrivalent or live-attenuated vaccines was not assessed. The researchers did not evaluate flu-related hospitalizations or deaths, which were too rare to analyze. The study also excluded children and the elderly and could not capture home-diagnosed cases outside the Cleveland Clinic system. Despite these limitations, its findings remain highly relevant to adult public health policy.
The results should be peer reviewed.
Conclusion & Implications
This hard-hitting real-world analysis suggests the 2024–2025 flu vaccine not only failed to protect working-age adults but may have increased their risk of infection. In an era of mounting skepticism and vaccine fatigue, public health authorities must reckon with data like this—not dismiss it. Annual flu vaccine strategies may need a serious rethink, particularly in years of poor strain matching. At minimum, real-time effectiveness tracking should become a national imperative, not an afterthought.
Nabin K. Shrestha, MD
Lead Research/Investigator
Nabin K. Shrestha, MD, Departments of Infectious Diseases, Cleveland Clinic
Patrick C. Burke, Infection Prevention, Cleveland Clinic
Amy S. Nowacki, Quantitative Health Sciences, Cleveland Clinic
Steven M. Gordon, Departments of Infectious Diseases, Cleveland Clinic
Source: Shrestha et al. (2025). Effectiveness of the Influenza Vaccine During the 2024-2025 Respiratory Viral Season. medRxiv. DOI:
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