Study Finds New Insights in Young Adults Who Develop Myocarditis After COVID-19 Vaccination

Research into young adults who develop myocarditis following COVID-19 vaccination has found new insights, including elevated levels of the spike protein and increased cytokines and troponin.

Despite these findings, the researchers emphasize that the risk of severe COVID-19 continues to outweigh the rare risk of post-vaccination myocarditis. Their findings do point to a potential treatment to prevent or reverse this rare condition, according to the study.

“The risk of developing severe disease from acute infection significantly outweighs this rare risk” said co-corresponding author Lael Yonker, MD, a pediatric pulmonary medicine specialist at Mass General for Children, in a press release. “While this finding helps us better understand this potential complication, it does not alter the risk benefit ratio of receiving the COVID vaccines. The incidence of myocarditis and other heart-related complications among children infected with SARS-CoV-2 is much higher than the risk of post-vaccination myocarditis.”

Myocarditis is a condition in which the heart muscle becomes inflamed, and it can rarely occur after vaccination with an mRNA COVID-19 vaccine. An estimated 18 cases occur in every 1 million administered doses, making it so rare that it can be challenging to find cases to investigate. In the new study, however, investigators analyzed the immune response of 16 adolescents and young adults who developed myocarditis after receiving the COVID-19 mRNA vaccine.

The team examined blood samples collected from 61 adolescents and young adults, including 16 who developed myocarditis and 45 who had no complications following vaccination with either the Pfizer or Moderna COVID-19 vaccines. They performed antibody profiling, including testing for SARS-CoV-2 specific humoral responses and assessment for autoantibodies or antibodies against the human relevant virome, SARS-CoV-2-specific T cell analysis, and cytokine and SARS-CoV-2 antigen profiling.

The researchers found no differences in antibody production, auto-antibodies, T cell profiles, or prior viral exposures, but found elevated levels of spike protein as well as increased cytokines and troponin. The cytokine levels are consistent with innate inflammation, whereas the increased troponin indicates cardiac injury, according to the study.

Antibody responses and T cell responses were essentially indistinguishable between cases and controls, according to the study. Using a test for detecting single molecules, the team found that adolescents who developed myocarditis had markedly higher levels of full-length spike protein in their blood. Adolescents in the asymptomatic, vaccinated control group had no detectable spike protein.

The team also looked for anti-N immunoglobulin G, an immunological marker of recent SARS-CoV-2 infection. This was undetectable, suggesting that natural infection was unlikely a contributing factor.

“Understanding the mechanisms that drive post-vaccine myocarditis could guide vaccine development in the future and give us important insights about the immune response,” said co-corresponding author David Walt, PhD, a professor in the Brigham’s Department of Pathology, in the press release. “This was a precious sample set because these cases are so rare. We studied them in great depth, which led to an interesting finding that could guide treatment strategies to reverse post-vaccine myocarditis.”

Although the study adds new insights about post-vaccination myocarditis, the authors noted that it is limited but small sample size and cannot distinguish between cause and consequence. In other words, it is unknown whether the spike protein itself is causing inflammation to the heart muscle or is a biomarker of immune dysregulation that leads to myocarditis.

“In most cases, post-vaccination myocarditis is mild and self-resolving,” Yonker said in the press release. “But new insights about its cause could further help us to improve patients’ symptoms or prevent this complication from occurring.”

REFERENCE

Researchers Study Immune Response, Proteins in Blood of Young Adults Who Develop Rare Complication After COVID Vaccination. News release. Mass General Brigham; January 4, 2023. Accessed January 10, 2023. https://www.massgeneralbrigham.org/en/about/newsroom/press-releases/myocarditis-after-covid-vaccination-study