Circulation: Immune response and proteins in the blood of young people who develop rare complications after COVID mRNA vaccination

• The risk of severe COVID-19 continues to outweigh the rare risk of myocarditis after vaccination

• In adolescents and young adults who developed this rare complication, the researchers found no difference in antibody production, autoantibodies, T cell profiles, or prior viral exposure, but detected elevated spike protein levels

• The findings point to potential treatments to prevent or reverse post-vaccine myocarditis

Myocarditis is a condition of myocardial inflammation that is a rare complication
that can occur after receiving the mRNA COVID vaccine.
It is estimated that about 18 cases occur per 1 million doses of vaccine, making them so rare that it is difficult to find cases to investigate
.
In a new study conducted by researchers at Brigham General Hospital in Massachusetts, founding member of Brigham General Hospital and researchers at Brigham Women's Hospital and Massachusetts General Hospital, a team extensively investigated the immune response of 16 adolescents and young adults who developed myocarditis
after receiving the COVID mRNA vaccine.
The researchers found no difference in antibody production, autoantibodies, T cell profiles, or prior viral exposure, but found elevated spike protein levels, increased cytokines (consistent with congenital inflammation), and increased troponin (indicating heart damage).

Their findings were published in the journal Circulation
.

"The risk of acute infection leading to severe disease greatly outweighs this rare risk," said
co-corresponding author Lael Yonker, MD, a pediatric pulmonary medicine specialist at Children's General Hospital of Massachusetts.
"While this finding helps us better understand this potential complication, it does not change the risk-benefit ratio
of receiving a COVID vaccine.
" In children infected with SARS-CoV-2, the incidence of myocarditis and other heart-related complications is much higher than the risk
of myocarditis after vaccination.
”

Patients with myocarditis can be treated with steroids to reduce inflammation, with largely good early outcomes
for young people and adolescents who develop this condition after vaccination.
The new study may point to other ways
to treat and improve outcomes for patients with myocarditis after vaccination.

"Understanding the mechanisms that drive post-vaccine myocarditis could guide future vaccine development and provide us with important insights into the immune response," said
co-corresponding author David Walt, Ph.
D.
, professor in the Department of Pathology at Brigham.
"It's a precious sample set because these cases are very rare
.
We conducted an in-depth study of them and came up with an interesting finding that could guide treatment strategies
for reversing post-vaccine myocarditis.
”

Blood samples were collected from 61 adolescents and young adults, 16 of whom had myocarditis and 45 had no complications
after receiving Pfizer BNT162b2 or Moderna mRNA-1273 COVID-19 mRNA vaccines.
The team performed antibody analysis, including detection of SARS-CoV-2-specific humoral responses, evaluation of autoantibodies or antibodies against human associated viral populations, SARS-CoV-2-specific T cell analysis, cytokines, and SARS-CoV-2 antigen analysis
.
Antibody responses and T cell responses differed largely between the case and control groups
.
Using Simoa, an ultrasensitive test used to detect single molecules, the team found that adolescents with myocarditis had significantly higher levels of the full-length Spike protein in their blood
.
Spike protein
was not detected in adolescents in the asymptomatic vaccination control group.
The team also tested for anti-N-IgG, an immunological marker of recent SARS-CoV-2 infection, but was not detected, suggesting that natural infection is unlikely to be a causative factor
.

While this study adds new insights into post-vaccination myocarditis, the authors note that it is limited by a small sample size and cannot distinguish between cause and effect; That said, it's unclear whether the spike protein itself is the cause of myocardial inflammation or a biomarker of immune dysregulation that causes myocarditis
.

"In most cases, post-vaccination myocarditis is mild and resolves
on its own," Yonker said.
But new insights into its causes can further help us improve our patients' symptoms or prevent this complication from occurring
.
”