A bombshell study by the Cleveland Clinic reveals that the 2024-2025 influenza vaccine may heighten, not reduce, infection risk in healthy working-age adults.
The findings, published on April 2, 2025, challenge long-held assumptions about flu shots and are sparking heated debate among health experts and the public alike.
The study, titled “Effectiveness of the Influenza Vaccine During the 2024–2025 Respiratory Viral Season,” tracked 53,402 employees of the Cleveland Clinic Health System in Ohio over a 25-week period starting October 1, 2024. Researchers, led by epidemiologist Dr. Nabin Shrestha, aimed to measure how well the flu vaccine worked in a real-world setting.
Unlike typical vaccine trials, this was a prospective cohort study, meaning it followed participants over time to compare flu outcomes between those who got the shot and those who didn’t. Researchers compared flu infection rates between vaccinated and unvaccinated healthcare workers, expecting to confirm the vaccine’s protective edge. Instead, they uncovered a troubling trend: those who got the flu shot were more likely to contract the virus.
Among the 32,155 vaccinated employees, 614 tested positive for influenza, compared to 532 cases among the 21,247 unvaccinated. After adjusting for factors like age, sex, and prior vaccination history, the study calculated a vaccine effectiveness of negative 27%. In plain terms, vaccinated individuals faced a 27% higher risk of flu infection than their unvaccinated peers. The risk was even starker for influenza A, the dominant strain, with a negative 33% effectiveness.
Dr. Shrestha’s team didn’t mince words about the implications. “These findings suggest that the influenza vaccine may not confer the expected level of protection,” they wrote, noting that vaccinated individuals also reported slightly more symptomatic illness, like fever and body aches, when infected. “This is a wake-up call,” said Shrestha, “We need to understand why the vaccine performed this way this season.” Flu vaccines are reformulated yearly based on global surveillance, but predicting dominant strains is notoriously tricky.
The findings hit hard because the study population, healthcare workers aged 18 to 64, was presumed to be healthy and responsive to vaccination. Unlike older adults or children, who face varying immune challenges, this group should theoretically show stronger vaccine benefits. Yet, the data tells a very different story.
Vaccinated workers didn’t just lack protection; they appeared more vulnerable, raising questions about the vaccine’s design or its interaction with immune systems primed by prior shots or infections.
Critics of the study, however, urge caution. Dr. Helen Chu, a flu expert at the University of Washington, argues that unmeasured factors, like workplace roles or testing habits, could muddy the results. Still, the Cleveland Clinic’s reputation and the study’s large sample size lend weight to its conclusions.
It used a prospective cohort design, tracking participants in real-time, and relied on PCR-confirmed flu cases, considered a gold standard for diagnosis. Unlike smaller trials, this scale offers a rare glimpse into vaccine performance in a real world setting, where flu strains evolve rapidly, and human behavior complicates outcomes.
The implications are thorny. Flu vaccines have been considered a cornerstone of public health, recommended annually for nearly everyone over six months old. But a negative efficacy, where the vaccine might worsen outcomes, erodes trust, especially among healthcare workers mandated to get the shot. Some employees shared anecdotes of better health after skipping flu shots, though experts warn personal stories don’t equal causation.
What’s next? The researchers call for urgent follow-up studies to confirm the findings and probe why the vaccine faltered. Theories include “antigenic drift,” where circulating viruses diverged from vaccine strains, or immune interference from repeated vaccinations, a phenomenon seen in some prior flu seasons. The World Health Organization’s strain selection process, finalized months before the season, may also need a rethink to keep pace with fast-mutating viruses.
For healthy adults, the data raises tough questions about one-size-fits-all mandates. As flu season presses on, the Cleveland Clinic’s bombshell is forcing a hard look at a tool long taken for granted.