FDA: mRNA COVID Shots Cause Myocarditis

Thank you all for coming. I'm going to be discussing the safety label update for myocarditis associated with mRNA COVID vaccines, which we just put forward. This came out on June 25th, 2025. The FDA approved a required updated warning, which is a class warning for all mRNA COVID-19 vaccines, in conjunction with the manufacturers.

I'm going to walk you through the updated warning and the basis for the warning. First of all, I'd like to thank David Kaslow and the vaccine team, and Richard Forshee and the pharmacovigilance team, for writing, coordinating, and deploying this safety label change. I'd also like to note this SLC was initiated prior to my joining the agency, and note I'm not using the FDA branch abbreviations in the hopes that this presentation will be more accessible to the general public.

The updated safety label for the mRNA COVID vaccines harmonizes the age range across products and adds additional data about the adverse event of myocarditis and what we know. It's based on two factors. It's based first on the unadjusted crude incident rate from the 2023 to 2024 formulation, and it's also based on persistent and concerning cardiac MR findings.

So, this is a slide that we put together. This is the FDA analysis of the BEST system, which is an observational data system that captures myocarditis and pericarditis following, immediately afterward, the first seven days of COVID-19 mRNA vaccination. And what you see here is that even in 2023–2024, the last year for which we have data, you see a rate of myo and pericarditis of 8 out of a million in all persons in this age range. And in the highest risk demographic group, young men between the ages of 12 and 24, it's about 27 per million.

Notably, the BEST dataset does not allow us to disambiguate the risk by product, and as such, this is a class mRNA safety label.

The second piece of evidence that is captured in the new safety label update is some concerning findings we've noted with late gadolinium enhancement. Now, late gadolinium enhancement is a radiographic abnormality seen on cardiac resonance imaging, and this is how it's been described prior to in the literature in the context of myocarditis: mild, sorry—patchy myocardial and focal subepicardial enhancement—as an expression of potentially irreversible injury, is how it's been described.

The FDA notably funded a study led by Jane and colleagues in 2024, which showed among hospitalized patients with COVID-19-induced myocarditis a high proportion—the majority—had initial late gadolinium enhancement on cardiac MR. The most concerning: at five months of follow-up, 60% of these patients continued to have LGE. And our results for late gadolinium enhancement are consistent with many, many others, as I'll show you here.

This was a study from Australia that followed six months post-COVID-19 vaccine-induced myocarditis. Over half of the patients were still reporting symptoms. 67% had abnormal follow-up cardiac MRs, and 35% showed what was listed as evidence of fibrosis.

I did a quick systematic review, pulling all available publications documenting a late gadolinium enhancement, and these are some takeaway summaries: 92% is occurring in men. 90% had LGE at presentation. But most concerning, 72% have persistent LGE even months thereafter.

Very consistent with the FDA-sponsored study, late gadolinium enhancement is not a benign clinical finding. Multiple studies document that LGE is a poor prognostic factor—that’s in many cardiac settings, including for patients with myocarditis. LGE has been associated with increased future cardiovascular events and even increased mortality.

We do not know the precise implications for LGE from vaccine-induced myocarditis, in part because the follow-up is necessarily so limited.

For this reason, the U.S. FDA and the sponsors have issued an SLC with the following two main points:

1. The updated, unadjusted incidence of myocarditis and/or pericarditis was approximately 27 per million—or 1 in 37,000—in males 12 to 24 years of age for the 2023 to 2024 formulation.
   
   

2. At a median follow-up of approximately five months post-vaccination, persistence of abnormal cardiac magnetic resonance imaging findings that are a marker for myocardial injury was common.
   
   

So, that's our class safety warning. And I think it's an important warning that was issued with the hard work of the team here.

And I want to take a minute to talk a little bit about the history of COVID-19 vaccine-induced myocarditis.

The background and history: the first reports of this phenomenon actually came to us by way of Israel. As many of you know, Israel aggressively partnered with Pfizer to have a large, wide-scale distribution of the mRNA vaccines. And the first reports were reported in the Jerusalem Post in February of 2021, that a young man had been admitted to the intensive care unit with myocarditis after the vaccine.

In February 2021, myocarditis safety signals were triggered in the VAERS dataset, and this is a nice timeline put together by a reporter of COVID-19 vaccines and myocarditis. By April 2021, there were at least two deaths and 60 cases reported from Israel. And the reports said that these details had been sent to the U.S. FDA and the CDC.

And yet, by April 27th, 2021, then CDC director said regarding this phenomenon, quote: “We have not seen a signal, and we've actually looked intentionally for the signal in the over 200 million doses we've given.” Yet at this time, the CDC was aware of 14 cases of post-vaccine myocarditis reported by the Department of Defense.

The Department of Defense would be one of the first to publish this phenomenon: myocarditis following immunization with many COVID vaccines among military members. And these early reports documented rather consistently an elevation in myocarditis risk—particularly to men, particularly for dose two.

The CDC, initially in the first half of 2021, had planned a Health Alert Network action, which ultimately was not released. And this occurred through the following series of events, which were obtained through FOIA-obtained emails. In May 2021, vaccine safety meeting, which included FDA and CDC officials, includes the following draft notes: “Quote: is VAERS signaling for mild pericarditis now?” And the answer: for the age group 16 to 17 and 18 to 24: “Yes.”

On May 25th, 2021—one day following the meeting where the FDA and CDC officials acknowledged the safety concern—the Biden White House distributed talking points to top health officials downplaying the risk of myocarditis.

On May 26th, 2021—two days after that meeting—then-acting FDA commissioner and CDC director note, quote: “The FDA does not concur with the issuance of the Health Alert Network,” and instead it was published as a less formal clinical consideration on the website.

The rates of post-vaccine myocarditis in men between the ages of 13 and 24 from 2021 have been documented in a number of publications and public documents.

In August of 2021, in an FDA regulatory action, we documented that based on health insurance claims, Optum dataset, the rate of post-vaccination myocarditis from the Pfizer-BioNTech vaccine was approaching 200 cases per million—or approximately 1 in 5,000.

A prospective study in Hong Kong published in 2021 showed post-vaccination myocarditis was approximately 1 in 3,000 for the second Pfizer dose in 13- to 18-year-old men. And using the VSD (Vaccine Safety Datalink) data, Schaff and colleagues showed approximately 1 in 2,000 risk of post-second mRNA dose in 18- to 24-year-old men.

There's an elegant analysis put together by the team led by Tracy Beth Hogue and others of post-vaccine myocarditis rates reported in 2021. And basically, you see across different demographic categories, with the far right being men between the ages of 12 and 17, an elevated risk that in some publications exceeded 300 per million.

Active surveillance from Hong Kong confirmed a broadly similar risk: men between the ages of 13 and 18, 1 in 2,700 had experienced myocarditis and were hospitalized following dose two of the Pfizer product.

And the Vaccine Safety Datalink, in a very interesting analysis by Scharf and colleagues, was found to have initially missed 64% of myo and pericarditis cases. The authors note, quote: “An incomplete list of ICD-10 codes and delays in hospital claims data were responsible for the difference between the VSD reported estimate and a careful chart review estimate.”

Stratification by demographic factors is key to unpacking the myocarditis risk from COVID-19. And an analysis led by Benjamin Knutson and myself, prior to joining the FDA, we analyzed publications that examined the risk of vaccines and myocarditis that had zero stratifiers—in other words, looking at all the doses given and the entire population—all the way to four stratifiers, which included looking only at men in certain age ranges, and only certain products, and certain doses. And as you can see, there is an association between looking in the right subpopulation—where this is a known safety concern—and the actual rate with which you'll find the safety signal.

VSD chart review from myo and pericarditis for the first Pfizer booster documented a rate slightly lower than the initial estimates, but 1 in 6,800. In another analysis led by Scharf and colleagues from Kaiser Permanente, some analysts based on these emerging safety signals have argued for years that there was some concern about mandatory coercive boosting—particularly of young men, particularly those who may have also recently had COVID-19.

And you can see among the authors of one such analysis, there are many names that may be familiar to you. The United States, in general, I think, exhibited some potentially missed opportunities for engaging in mitigation on this important safety risk.

Notably, spacing the doses of the first two doses further apart was a strategy deployed in Europe approximately one year before the CDC allowed providers to consider it. Another strategy was specific products were restricted for use in the under-30-year-old age group in multiple European countries. That action was never taken in the United States.

Severity and long-term sequela: the CDC data published from a few years ago in 2022 documented clinical outcomes 90 days after post-vaccination myocarditis in 12- to 29-year-olds. Notably, at presentation—this is from various submissions, so there is a reporting element to this—at presentation, 25% of these patients were initially admitted to the intensive care unit. One patient required extracorporeal membrane oxygenation, or ECMO.

At 90 days after diagnosis, over 25% continued to be prescribed cardiac medications. Over 30% remained on activity restrictions to avoid strenuous exercise. Over half of these patients had more than one persistent abnormality on cardiac MR. Only 66% of these patients were known to have fully recovered, and 17% had not fully recovered by three months.

There have also been reports of deaths due to fulminant myocarditis. This is one report in New England Journal of Medicine. There are several other reports.

As is the case with all idiosyncratic adverse events, these are likely to exist on a spectrum. There's undoubtedly some people who have mild or subclinical myocarditis, and undoubtedly also some deaths may be implicated. And we, in our own sponsored data, find that 2% of hospitalized patients required inotropes.

Myocarditis from vaccines is a distinct clinical entity, likely immunologically mediated.

Many analysts have compared this vaccine-induced myocarditis against myocarditis following COVID-19 infection. Yet many of these studies failed to disambiguate myocarditis after COVID-19 infection versus troponin elevations seen in the setting of severe illness. Furthermore, patients—many—can still get COVID-19 at some distance after vaccination, accepting the risks of both the vaccine product and the illness. Though very likely, the illness—the former—is mitigated. Though also plausibly, there may be a ceiling to that mitigation with additional doses.

Hospitalizations from COVID often fail to disambiguate COVID-19 being the cause of hospitalization versus COVID-19 being a bystander diagnosed at hospitalization. The rates of COVID-19 severe outcomes are declining, with widespread vaccine and natural immunity and the evolving nature of the virus. And as such, the FDA will perform a new benefit-risk assessment in this target group to continue to reassess the benefit-risk balance.

Take-home points: the FDA concludes that the 2023 to 2024 mRNA vaccines have an unadjusted crude risk of myocarditis of 27 per million in young men. This risk has persisted across all of the doses of the product that we've examined. Vaccine-induced myocarditis, when leading to hospitalization, is associated with baseline and persistent late gadolinium enhancement in the majority of patients in our funded study. LGE is a known poor prognostic marker generally, though the full implication of it is unknown in this specific setting.

Because of these factors, an SLC was issued. The FDA SLC was initiated by career FDA staff. It represents the latest action by FDA to accurately convey the safety of these products. This may not be the final action, which is contingent on further data. The U.S. FDA will not negotiate on safety.

Because of these factors, the commissioner and I outlined a COVID-19 vaccine framework in the New England Journal of Medicine, which broadly will require randomized controlled trials before extending additional delays and space to healthy Americans under the age of 65. At the same time, our framework will continue to provide additional doses to vulnerable populations based on immunogenicity.

Providers should consider recent COVID-19 infection, the absolute risk of severe COVID-19, and recent safety label changes when pursuing COVID-19 vaccination, particularly in young men.

Public trust: public trust is delicate. In order to regain it, the FDA will pursue safety signals with the best available scientific methods and ensure that our marketing authorizations are made only to populations where we have substantial confidence the benefits outweigh the risks. Our recent SLC action is a step towards rebuilding public trust.

So, thank you all for your time and attention. We're going to stop the recording, and then we're going to turn it over to Dr. Butler for some operational matters. Thank you.