Two studies published this week suggest that updated COVID-19 booster vaccines continue to provide meaningful protection against major adverse outcomes, cardiovascular complications, hospitalization, and all-cause death, even as both the virus and the population’s immune status have evolved and the protections conferred by the booster have become more modest.
The studies offer a broad look at the impact of 2024-25 COVID vaccines six years after the initial phase of the pandemic and as politicization of the COVID booster, and mRNA vaccines in general, persist.
“National views on this issue are being shaped by a combination of the general antivaccination statements from the US Department of Health and Human Services, encouragement for vaccination from every mainstream medical and public health professional society, and the complex new arena of social media,” writes Robert M. Califf, MD, of the Division of Cardiology at Duke University and former Food and Drug Administration commissioner, in a commentary accompanying the studies.
But, he said, “the toll of death and disability from COVID-19 continues to drop, so it should no longer be treated as exceptional but as one of many infectious diseases for which vaccination is protective.”
The studies and commentary were published in JAMA Internal Medicine.
Lower risk of severe disease
In one study, a team led by researchers from the Centers for Disease Control and Prevention (CDC) analyzed about 431,000 emergency department visits and hospitalizations across more than 380 emergency department/urgent care (ED/UC) departments in six states to evaluate the effectiveness of the 2024-25 vaccine.
The researchers analyzed data from adults with and without compromised immune systems from September 2024 to September 2025.
Among immunocompetent adults, vaccination reduced the likelihood of COVID-related ED/UC visits by 26%, hospitalizations by 35%, and COVID-associated critical illness by 41% compared with people who had not received the updated vaccine.
The vaccine was most effective during the first two months after vaccination and waned over time. Protection against ED/UC visits, for example, declined from 38% seven to 59 days after vaccination to 11% after 180 to 299 days.
The toll of death and disability from COVID-19 continues to drop, so it should no longer be treated as exceptional but as one of many infectious diseases for which vaccination is protective.
Among immunocompromised adults, vaccine effectiveness (VE) against hospitalization was 24% and also waned over time, dipping to no protection 180 to 299 days after vaccination.
“Results of this study demonstrate that COVID-19 vaccines continued to provide benefit to people at the highest risk of severe COVID-19 outcomes,” write the authors, concluding that “receipt of 2024-2025 COVID-19 vaccination was associated with additional protection against medically attended COVID-19 beyond an individual’s existing immunity; however, protection appeared to wane over time.”
Reduced cardiovascular risk in older adults
A second study, led by researchers at the US Department of Veterans Affairs, examined whether the 2024-25 vaccine was tied to a lower risk of COVID-19–associated major adverse cardiovascular events (MACE), which include cardiovascular death, heart attack, stroke, and hospitalization for heart failure.
Using health records from more than 1 million veterans who received the flu vaccine from September to December 2024, the researchers compared people who received a COVID vaccine at the same time as a flu vaccine with those who received only the flu vaccine.
After eight months, receipt of the COVID vaccine was associated with a 37.7% reduction in MACE, but VE was statistically significant only in adults older than 75 years, who experienced a 50.7% reduction in MACE as well as the largest absolute risk reduction.
While the researchers observed statistically significant VE in both those with and without comorbid conditions, the absolute benefit was “consistently and substantially greater” for those who had other chronic conditions.
“While the reduction in COVID-19–associated MACE was modest, the substantially larger reduction in all-cause MACE suggests that the vaccine’s protective association extends to the hidden burden of undetected SARS-CoV-2 and its sequelae,” write the researchers.
Benefits outweigh risks
Despite all Americans having been either infected with and/or vaccinated against COVID at this point, writes Califf in the commentary, the studies’ findings demonstrate that “updated booster vaccines provide continued protection against major adverse clinical outcomes, including lower risks of major cardiovascular events, hospitalizations, and all-cause death.”
And even though the magnitude of the protection is modest and wanes over time, argues Califf, the cardiovascular benefits of vaccination outweigh the potential risks. What’s more, he adds, studies continue to suggest major risks tied to COVID infection, including neurodevelopmental disorders in children born to those with serious COVID infections.
Post-COVID condition, also known as long COVID, is another important consideration. “Ongoing studies point out the substantial effects of post–COVID-19 condition. Millions of individuals in the US, including a substantial number of children, experience loss of function and diminished quality of life due to the disease’s sequelae,” Califf writes. “Many observational studies have found an association between previous vaccination and a reduced risk of post–COVID-19 condition.”
Overall, the commentary argues, accumulating evidence supports COVID vaccination. “The studies reported herein, combined with previous data, provide strong evidence of a favorable balance of benefit to risk for updated COVID-19 vaccine boosters across the population,” he writes.
