Israel-Based Research Defines Myocarditis Risk Following Pfizer-BioNTech Vaccination

By Daniel K. Brantley

Evidence indicates the strongest connection between the vaccination and myocarditis is among males ages 16 to 29.

A retrospective review of clinical and laboratory data taken out of Israel indicates a connection between the BNT162b2 messenger RNA (mRNA) vaccine from Pfizer-BioNTech and cases of myocarditis. The study was timely, as there has been some intimation that such a connection exists.

Israel presents an ideal environment for this study for two reasons. First, the nation almost exclusively used the Pfizer-BioNTech vaccine. Second, as it is legally required to report all cases to the Israeli Ministry of Health, individuals who experience myocarditis symptoms while in Israel are hospitalized as matter of course. As a result of these factors, it’s possible to achieve accurate accounting of myocarditis incidents.

One piece of research, published in The New England Journal of Medicine, was led by Dror Mevorach, MD, who heads Hadassah Hospital Ein Kerem’s Internal Medicine Department. To date, this is the largest study ever performed regarding side effects and complications of vaccination using cardiac MRI to examine vaccine-related damage to heart muscle tissue. A second study, published in the same issue of The New England Journal of Medicine, was led by Guy Witberg, MD, member of the Cardiology Department at Beilinson Hospital in Petah Tikva, Israel. This study uncovered similar results based on data from Israel’s largest healthcare organization, Clalit Health Services, of which Beilinson Hospital is a part.

Speaking to Science, Dr. Mevorach said his research findings are “very suggestive of a causal nature,” continuing that he is “convinced there is a relationship.”

Seeking Answers

While rare, the risk of developing myocarditis via Pfizer-BioNTech vaccination does exist. This should be considered when caring for patients at risk for cardiovascular disease. And while the risk has been confirmed, a number of unanswered questions remain. These include the following:

  • Would a longer period between vaccine injections reduce the likelihood of myocarditis?
  • Do young men who develop the disease post-vaccination have other common traits (beyond age and sex) that, if recognized, researchers could exploit to protect other men from post-vaccination myocarditis?
  • Do other COVID-19 vaccines carry an increased risk of myocarditis similar to the Pfizer-BioNTech offering?

Statistically Significant

Dr. Mevorach’s team studied all cases of myocarditis reported to the Israeli Ministry of Health from Dec. 20, 2020, through May 31, 2021. Of 5.1 million fully immunized Israelis (having received both Pfizer-BioNTech injections, with 21 days between vaccinations), 304 presented with myocarditis symptoms. The main symptom was chest pain.

“We dissected every case,” Dr. Mevorach told Nature.

Twenty-one individuals experienced conditions other than myocarditis, and 142 experienced their initial symptoms post-vaccination. From this group of 142, 136 received a definitive or probable diagnosis of myocarditis. One of these individuals had fatal complications, and 129 experienced mild symptoms of the disease. During the same time period, Dr. Mevorach’s team also uncovered 101 myocarditis diagnoses in unvaccinated people. Of these, 29 were confirmed to have COVID-19.

The group at highest risk for post-vaccination myocarditis was 16- to 19-year-old males (13.73 per 100,000). The rate ratio among this population a month after the second dose was 8.96, whereas the rate ratio among their unvaccinated peers was 2.35.

Dr. Witberg’s study, though smaller in scale, had equally significant results. It reviewed the data of 2.5 million vaccinated patients who used Clalit Health Services. Within this smaller study group, 2.13 cases of myocarditis were confirmed per 100,000 individuals. As with the other research, young males were at greatest risk (10.69 per 100,000 vaccinated males ages 16 to 29), and the majority of cases were mild or moderate.

According to Ran Kornowski, MD, fellow researcher at Beilinson Hospital, these findings are significant. He told The Times of Israel that the vaccine has a “proven huge benefit in preventing coronavirus illness and its many consequences.” He hopes this new research will help more people make an appropriate choice concerning whether or not to undergo vaccination.

Assessing the Risk

When a link between vaccination and myocarditis was initially posited, researchers considered reasons why such a link would exist, if it did. To date, the cause of the link is unclear. According to a study reported in the American Heart Association’s Circulation, “immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed” as possible causes.

Compared to the overall risk of myocarditis (.01–.02%), the additional risk of vaccine-induced myocarditis is small. According to Dr. Witberg’s comments to The Times of Israel, this is good news.

“The findings show this is a relatively rare occurrence,” he says, “even in the population at greater risk — young men.”

Contracting COVID-19, on the other hand, increases the risk of myocarditis greatly. Within the United States, the CDC reports that myocarditis risk among hospitalized COVID-19 patients is nearly 16 times (0.146%) that of the general population. Previous research from the Clalit Health Services published in The New England Journal of Medicine found even greater risk. According to their study, individuals who contract COVID-19 are 18 times more likely to experience subsequent myocarditis than those who do not get infected.

Benefits Outweigh Risks

While research is ongoing in the United States to determine if myocarditis risk increases with the use of Moderna’s mRNA vaccine, Dr. Mevorach insists that the benefits of vaccination outweigh risks among individuals age 16 and over. The CDC, AAFP and multiple other national organizations continue to recommend vaccination for COVID-19.