Updated COVID shot still cut severe disease, cardiac risk

Clinical takeaway: Recommending an updated vaccine remained justified, with the clearest benefit in older and higher-risk patients. Expect protection against COVID to wane after about six months.

Most US adults now carry immunity from prior infection, vaccination, or both, raising the question of whether an updated COVID shot still adds any benefit. Two JAMA Internal Medicine studies, one tracking severe COVID and another cardiovascular events, took up different aspects of this assessment.

The 2024-2025 formulations were approved in August 2024, with the CDC recommending a dose for most adults and an additional dose for those 65 and older or immunocompromised. By late 2023, an estimated 87% of US adults showed evidence of prior infection and circulating variants had grown milder.

In the CDC analysis of immunocompetent adults, the updated vaccine was tied to lower odds of medically attended COVID, with effectiveness rising as illness grew more severe: 26% against emergency or urgent care visits, 35% against hospitalization, and 41% against critical illness over the 7-to-299-day window.

Protection faded with time. Effectiveness against hospitalization ran 51% in the first two months but fell to roughly zero after about six months, a pattern similar across age groups. In a separate analysis on immunocompromised adults, protection was lower but still present at 24% against hospitalization.

The VA study, comparing veterans who received the COVID and flu vaccines together against those who got flu vaccine alone, tied the shot to a 37.7% lower risk of COVID-associated major adverse cardiovascular events, or MACE. But the absolute reduction was small with about 2 fewer events per 10,000 people, and reached significance only in those older than 75. The larger signal was in all-cause MACE, where the absolute reduction was roughly 24 per 10,000, which the authors read as the vaccine capturing cardiovascular events triggered by undetected infection.

The CDC study used a test-negative case-control design within VISION, a six-state network of 381 emergency or urgent care sites and 246 hospitals, comparing vaccination odds among adults who tested positive for SARS-CoV-2 against those who tested negative. The VA study emulated a target trial in more than 1 million veterans, using inverse probability weighting to balance the two vaccine groups.

"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. But the differences, especially in low-risk populations, are small," said Robert Califf, M.D., former commissioner of the U.S. Food and Drug Administration and a cardiologist at Duke University School of Medicine, in an accompanying editorial.

Source: Wiegand RE. JAMA Intern Med. 2026 Jun 15. Estimated effectiveness of 2024-2025 COVID-19 vaccines in adults; Cai M. JAMA Intern Med. 2026 Jun 15. 2024-2025 COVID-19 vaccine and major adverse cardiovascular events among US veterans