IDWeek 2025: No signal for myocarditis in updated Moderna mRNA COVID vaccine

The updated 2024-2025 mRNA COVID vaccine from Moderna does not appear to carry the same risk for myocarditis in young adults that the first mRNA COVID vaccines did, suggested research presented at the Infectious Disease Week (IDWeek) 2025 Annual Meeting in Atlanta, Georgia.

“The mRNA-1273 vaccine continues to have an acceptable safety profile consistent with the product labeling,” Susan Pfeiffer, PA, director of clinical development at Moderna, manufacturer of the vaccine, told attendees. No adverse events were reported related to either the COVID vaccine or the placebo injection in the observed time periods after each, and no cases of myocarditis or pericarditis were reported in the study.

“We know that the COVID vaccine boosters don’t set off as much myocarditis when there is an interval greater than 8 weeks apart,” Frank Han, MD, pediatric cardiologist at Connecticut Children’s Medical Center in Hartford, Connecticut, told Medscape Medical News. “This result may reflect that.”

Han was not involved with this study but reviewed the data. He further noted, however, that “981 people may be a little too small to find vaccine myocarditis.”

Myocarditis is known to be a rare adverse event that can occur following mRNA COVID vaccination, though the risk for myocarditis is approximately seven times higher with SARS-CoV-2 infection than with vaccination, Pfeiffer told attendees.

However, published studies suggest the increased risk for myocarditis is primarily associated with the first and second doses of the primary series of the original vaccines.

Research looking at updated vaccine formulations, such as the bivalent vaccine targeting both the original SARS-CoV-2 virus and the Omicron variant, were linked to lower risks for myocarditis. A study last year, for example found that the reporting rate of myocarditis or pericarditis in the Vaccine Adverse Event Reporting System (VAERS) was 6.91 per million doses with the original mRNA vaccines but 1.24 per million doses with the bivalent vaccine.

Data from VAERS cannot be used to establish causation or risk since it is a passive surveillance system, but other research has similarly found lower rates of myocarditis or pericarditis with a third or later dose of mRNA COVID vaccines.

In this new study, researchers from Moderna used a biomarker to look for potential signals of cardiac effects in those receiving the Moderna mRNA COVID vaccine targeting the KP.2 variant. Cardiac troponin, though not specific to a diagnosis of myocarditis, is a serum biomarker for myocardial injury.

The researchers conducted a phase 4 randomized controlled, crossover study in 997 participants, aged 12-30, to compare troponin levels after receipt of Moderna’s 2024-2025 updated mRNA COVID vaccine. Elevated levels were defined as > 53.53 pg/mL for men and > 38.64 pg/mL for women.

Participants were initially randomly assigned to two arms, with half receiving the vaccine and half receiving a placebo. Then, 29 days later, those who received the vaccine received a placebo injection, and those who initially received placebo then received the vaccine. Observation of the participants then continued through day 57.

The 981 participants with evaluable data had an average age of 19.8 years, with just over half (54.6%) between 18-30 years old and 45.4% aged 12-17. Just over half were female (53.8%), and two thirds were White (65.1%), whereas 24.1% were Black, and 3.4% were Asian. Hispanic/Latino participants made up 14.8% of the cohort.

Most of the participants (98.2%) had no elevated levels of troponin during the study. Among the 18 participants (1.8%) who did have at least one elevated measure of troponin, seven showed elevated levels at baseline, before receipt of the vaccination. Among the 11 with normal levels at baseline, eight showed increased levels 28 days after receiving the placebo, and three showed higher levels 28 days after receiving the mRNA vaccine.

“Physical activity is a recognized physiological driver of troponin release,” Pfieffer said, with the levels varying by type, duration, and intensity of exertion in healthy people. The participants in this study therefore recorded their vigorous activity in vaccination diaries four days after injection 1, 4 days before and after injection 2, and 4 days before the last study visit. Among the 18 participants with elevated levels of troponin, 11 of them (61%) reported physical activity within these preinjection or postinjection windows.

The research was funded by Moderna. Pfeiffer and five other authors declared being employees of Moderna and holding stock or stock options in the company. Han had no disclosures. 

By Tara Haelle