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Detailed records showed that people diagnosed with myocarditis after COVID-19 vaccination tended to be men, and all were able to recover after a few days in the hospital.

Health officials around the globe are investigating the potential link between vaccines and inflammation of the myocardium, with the attention focused on the Pfizer/BioNTech and Moderna mRNA vaccines in particular.

Myocarditis had not been reported in clinical trials leading to the authorization of these vaccines.

Ahead of the Advisory Committee on Immunization Practices (ACIP) meeting on Friday -- during which CDC advisors are expected to review the several hundred cases of suspected myocarditis that have been reported by the public to the Vaccine Adverse Event Reporting System (VAERS) -- two case series and one in-depth case report were published online in Circulation.

None of these reports were able to definitively confirm or exclude a causal relationship between vaccination and myocarditis.

Eight Cases in the U.S. and Italy

The described eight patients from the U.S. and Italy who presented with chest pain and were diagnosed with acute myocarditis at an average of 3 days after getting an mRNA vaccine. All were otherwise healthy men ages 21 to 56 years.

Only one person experienced myocarditis after a first vaccination dose; this person had a previous infection from SARS-CoV-2.

Five of the eight patients had a fever within 24 hours of the injection (three with Moderna, five with Pfizer), with chest pain developing 48 to 96 hours later, reported a group led by Kathryn Larson, MD, of Mayo Clinic in Rochester, Minnesota.

Treatment included nonsteroidal anti-inflammatory drugs, colchicine, or prednisone. Three individuals received no medications.

All eight men had their chest pain resolved. They were discharged from the hospital in stable condition, and were alive with preserved left ventricular ejection fraction (LVEF) at last contact.

"No eosinophilia was noted in our patients, unlike myocarditis associated with smallpox vaccination. Potential mechanisms for myocarditis post-mRNA-based vaccination include a non-specific innate inflammatory response or a molecular mimicry mechanism between viral spike protein and an unknown cardiac protein," Larson and colleagues noted.

Seven Cases in Virginia and Texas

Myocarditis emerging after inoculation was not limited to the mRNA vaccines, according to a .

Seven people, all white or Hispanic men under age 40, presented with acute-onset chest pain 3 to 7 days after being vaccinated. Five had received the Pfizer mRNA vaccine, one received the Moderna mRNA vaccine, and one received the Johnson & Johnson adenovirus vaccine.

Lab and imaging findings were largely consistent with myocarditis. Endomyocardial biopsy was negative in the single case in which it was performed, though this may be explained by the patchy nature of myocardial inflammation in myocarditis, said Christopher deFilippi, MD, of Inova Heart and Vascular Institute in Falls Church, Virginia, and colleagues.

Patients received various treatments including beta-blockers and anti-inflammatory medications.

Chest pain was resolved by discharge following an average 3-day stay in the hospital (either at deFilippi's institution or the University of Texas Southwestern Medical Center in Dallas).

"Our series of seven male COVID-19 vaccination recipients who presented with myocarditis-like illness supports a potential causal association with vaccination given the temporal relationship, clinical presentation and CMR [cardiac MRI] findings," deFilippi's team wrote.

However, two people had no measurable spike protein IgG and had presented shortly after their first vaccine dose. "This antibody response is not unexpected, but may indicate an alternate vaccine-related immune mechanism or absence of causality with the vaccine," the authors noted.

One Case Adds Intrigue

Finally, the of a man with myocarditis-like illness after vaccination revealed a lack of the expected cytokine changes implicated in myocarditis.

As in the other reports, the 52-year-old previously healthy man developed chest pain days after being vaccinated with the second dose of the Moderna vaccine and had clinical and cardiac MRI findings consistent with myocarditis.

Like the others, this patient also had symptoms resolve quickly. "The patient's chest discomfort had fully resolved within 3 hours after onset and did not recur. He reported feeling normal throughout the remainder of his 4-day hospital stay," wrote James de Lemos, MD, of the University of Texas Southwestern Medical Center, and colleagues.

The patient was treated with low-dose lisinopril and carvedilol therapy. He had no recurrent symptoms after hospital discharge and remains on a beta-blocker and angiotensin-converting enzyme inhibitor therapy.

"The case does not prove a causal association between the vaccine and the observed myocarditis-like syndrome. However, ischemic injury and other potential causes of acute myocardial injury were excluded, as were other potential infectious causes of myocarditis, and there was no evidence of systemic autoimmune disease," noted de Lemos and colleagues.

However, the T helper 17 cell-related interleukin-17 enriched immune signature, observed in the development of myocarditis and the transition of fibrosis to heart failure, was not present in the patient. Instead, he showed increased NK cells and increased expression of several autoantibodies compared with controls.

These findings "could suggest a distinct vaccine-associated immunophenotype with a high likelihood for rapid recovery. However, it is not clear whether the observed differences reflect a potential (causal) pathologic immune response or rather appropriate healing responses to myocardial inflammation," the authors wrote.

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