The protective role of vitamin D in BNT162b2 vaccine-related acute myocarditis

Abstract

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.

Publication DOI: https://doi.org/10.3389/fimmu.2025.1501609
Divisions: College of Health & Life Sciences > Aston Pharmacy School
Funding Information: This work was supported by the Hong Kong Collaborative Research Fund (CRF) 2020/21 and CRF Coronavirus and Novel Infectious Diseases Research Exercises (Reference Number: C7149-20G), Health and Medical Research Fund (HMRF) (Reference Number: 18192311), an
Additional Information: Copyright © 2025 Tsang, Chua, Tung, Wong, Tsao, Wong, Tung, Kwok, Yam, Chan, To, Wong, Leung, Kwan and Ip. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Uncontrolled Keywords: vitamin D genetics,vitamin D deficiency,natural killer cell,vitamin D,hyperinflammation,BNT162b2 vaccine-related myocarditis,hypercytokinemia,mRNA COVID-19 vaccines
Publication ISSN: 1664-3224
Data Access Statement: The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.
Last Modified: 26 Mar 2025 17:01
Date Deposited: 07 Mar 2025 15:35
Full Text Link:
Related URLs: https://www.fro ... 25.1501609/full (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2025-02-19
Published Online Date: 2025-02-19
Accepted Date: 2025-01-27
Authors: Tsang, Hing Wai
Chua, Gilbert T.
Tung, Keith Tsz Suen
Wong, Rosa Sze Man
Tsao, Sabrina Siu Ling
Wong, Joshua Sung Chih
Tung, Joanna Yuet Ling
Kwok, Janette Siu Yin
Yam, Jason Cheuk Sing
Chan, Godfrey Chi Fung
To, Kelvin Kai Wang
Wong, Ian Chi Kei (ORCID Profile 0000-0001-8242-0014)
Leung, Wing Hang
Kwan, Mike Yat Wah
Ip, Patrick

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