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Spike Protein Detected in Post–COVID-19 mRNA Vaccine Myocarditis
Quick Takes
- This case-control study involving 16 young individuals with post–SARS-CoV-2 myocarditis and 45 healthy age-matched control participants sought to identify potential differences in immunologic profiles that would shed light on potential mechanisms or underlying predisposition factors to vaccine-induced myocarditis.
- The investigators performed extensive immunologic profiling including anti–SARS-CoV-2 antibody profiling, autoantibodies and antibodies against previous infections, SARS-CoV-2 spike protein-specific T-cell responses, and various cytokine measurements.
- There were no significant differences in mRNA vaccine-induced immune responses, with no difference in adaptive and T-cell immunity. Free spike antigen was detected in the blood of patients who developed post-mRNA vaccination.
Study Questions:
Is post–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination myocarditis linked to differences in immunologic profiles compared to age-matched vaccinated control subjects?
Methods:
The investigators collected blood samples from 16 adolescents or young adults (16-21 years of age) hospitalized for post–SARS-CoV-2 vaccine myocarditis at Massachusetts General for Children or Boston Children’s Hospital for myocarditis, in addition to 45 healthy, asymptomatic, age-matched vaccinated control subjects who received their second vaccination within 11 days. They performed several measurements including anti–SARS-CoV-2 antibody profiling, autoantibodies and antibodies against previous infections, SARS-CoV-2 spike protein-specific T-cell responses, and various cytokines.
Results:
The cohort of myocarditis patients consisted of mostly males (n = 13 of 16) who experienced myocarditis after the second dose (n = 12 of 16), within the first week after vaccination (median of 4 days). All patients had elevated cardiac troponin T levels (median 260 ng/L) and C-reactive protein levels (29.75 mg/L). Total neutrophil count was higher in patients with myocarditis compared to those without, albeit remaining in the normal range. Levels of full-length spike protein (33.9 ± 22.4 pg/mL), unbound by antibodies were markedly elevated in the plasma of individuals with postvaccine myocarditis, whereas no free spike was detected in asymptomatic vaccinated control subjects (unpaired t-test; p < 0.0001). Levels of free spike did not differ between males and females, and remained elevated for weeks in a subset of patients with repeated blood collections. With regard to T-cell responses, there were no major differences in various T-cell subsets (effector, effector memory, spike-specific, interferon-gamma and degranulating). There were no differences in antibody levels (anti-spike, anti-receptor binding protein, immunoglobulin [Ig] M, IgG, IgA, or anti-Fc), auto-antibodies, or antibodies to common respiratory pathogens. However, inflammatory cytokine levels were altered, with elevations in interleukin (IL)-8, IL-6, tumor necrosis factor-alpha, IL-10, interferon-gamma and IL-1-beta, reflecting innate inflammatory activation.
Conclusions:
SARS-CoV-2 mRNA vaccine–induced immune responses did not differ between individuals who developed myocarditis and individuals who did not. Free spike antigen was detected in the blood of adolescents and young adults who developed post-mRNA vaccine myocarditis.
Perspective:
This is a great example of a study with mostly negative findings which are, however, insightful. The investigators used a thorough approach in teasing out the various aspects that could underlie vaccine-induced myocarditis. In summary, the data show that adaptive and T-cell immunity responses were normal in recipients of mRNA vaccines, both with and without myocarditis. Patients who developed postvaccine myocarditis had persistently elevated free spike protein in circulation, which correlated with evidence of cardiac injury and inflammatory cytokines. The implications of this finding are unclear, since it is yet unknown how the spike protein evades cleavage or clearance, especially in the setting of a normal adaptive immune response, or whether in itself is pathogenic. Given myocarditis also occurs after other vaccines, it is likely that the presence of circulating spike is a biomarker rather than the causal agent. Indeed, presence of viral proteins has been associated with hyperinflammatory responses such as in severe COVID-19 or the notorious multisystem inflammatory syndrome in children (MIS-C). We are left with several hypotheses and more questions, but with a clear direction.
Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, COVID-19 Hub, Heart Failure and Cardiomyopathies, Prevention, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Adolescent, Autoantibodies, Biomarkers, COVID-19, COVID-19 Vaccines, C-Reactive Protein, Cytokines, Heart Failure, Immunoglobulins, Interferon-gamma, Interleukins, Myocarditis, Neutrophils, Primary Prevention, RNA, Messenger, SARS-CoV-2, Spike Glycoprotein, Coronavirus, T-Lymphocytes, Troponin T, Tumor Necrosis Factor-alpha, Vaccination, Young Adult
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