Introduction: Vaccine-related myocarditis is recognized as a rare but important complication, especially after mass-scale mRNA COVID-19 vaccination. Knowledge regarding how to minimize the risk is limited.
As NK cells can mediate acute myocarditis after mRNA COVID-19 vaccination and vitamin D may inhibit NK cells via cytokine modulation, we hypothesize that the myocarditis side effect is related to a hypovitaminosis D – mRNA vaccine – hypercytokinemia – NK cell axis, which is amendable to clinical intervention.
Methods: Biochemical, immunophenotypic and genotyping assays were performed to examine vitamin D status and immune profiles in 60 patients who had BNT162b2 vaccine-related acute myocarditis.
Results: A high incidence of hypovitaminosis D (73.3%) was observed in these individuals with vaccine-related myocarditis, particularly in those presented with chest pain or intensive care unit (ICU) admission. Moreover, vitamin D level was negatively associated with peak serum cardiac troponin T level during vaccine-related myocarditis.
Genotypically, the GC (vitamin D binding protein) rs4588T allele which encoded the GC2 isoform of vitamin D binding protein was a risk allele, whereas the GC1S isoform was protective.
Mechanistically, hypovitaminosis D was associated with higher levels of cytokines pivotal for natural killer (NK) cells (particularly interleukin-1β (IL-1β), IL-12, Interferon-γ (IFN-γ), and IL-8) and higher percentage of CD69+ NK cells in blood, which in turn correlated with chest pain presentation.
Conclusion: These data support the hypothesis that vitamin D plays a crucial role in mitigating mRNA vaccine-related myocarditis by modulating proinflammatory cytokine milieu and subsequent unfavorable NK cell activation, laying a groundwork for preventive and treatment strategies.
Key Findings
Vitamin D Deficiency is Common in Myocarditis Cases
73.3% of individuals who developed myocarditis after mRNA injection had low vitamin D levels (≤50 nmol/L).
Among those with vitamin D deficiency:
88.3% experienced chest pain, compared to those with normal vitamin D levels.
30% required ICU admission, indicating more severe cases.
Vitamin D May Reduce Risk
Higher vitamin D levels were linked to:
Lower inflammation in the heart (as indicated by lower cytokine levels).
Reduced activation of NK cells (fewer CD69+ NK cells).
Fewer severe symptoms of myocarditis (lower cTnT levels and fewer ICU admissions).
Patients with vitamin D sufficiency (>50 nmol/L) were less likely to experience severe symptoms (p < 0.05).
Lower Vitamin D = More Heart Damage
Patients with low vitamin D had higher levels of cardiac troponin T (cTnT), a marker of heart damage:
Vitamin D-deficient patients had an average cTnT of 0.62 ± 0.40 ng/mL.
Patients with sufficient vitamin D had significantly lower cTnT levels (p = 0.0099).
Vitamin D levels were negatively correlated with cTnT (r = -0.3053, p = 0.0221).
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