The central role of natural killer cells in mediating acute myocarditis after mRNA COVID-19 vaccination

Hing Wai Tsang, Mike Yat Wah Kwan, Gilbert T. Chua, Sabrina Siu Ling Tsao, Joshua Sung Chih Wong, Keith Tsz Suen Tung, Godfrey Chi Fung Chan, Kelvin Kai Wang To, Ian Chi Kei Wong, Wing Hang Leung, Patrick Ip

Research output: Contribution to journalArticlepeer-review


BACKGROUND: Vaccine-related acute myocarditis is recognized as a rare and specific vaccine complication following mRNA-based COVID-19 vaccinations. The precise mechanisms remain unclear. We hypothesized that natural killer (NK) cells play a central role in its pathogenesis. METHODS: Samples from 60 adolescents with vaccine-related myocarditis were analyzed, including pro-inflammatory cytokines, cardiac troponin T, genotyping, and immunophenotyping of the corresponding activation subsets of NK cells, monocytes, and T cells. Results were compared with samples from 10 vaccinated individuals without myocarditis and 10 healthy controls. FINDINGS: Phenotypically, high levels of serum cytokines pivotal for NK cells, including interleukin-1β (IL-1β), interferon α2 (IFN-α2), IL-12, and IFN-γ, were observed in post-vaccination patients with myocarditis, who also had high percentage of CD57 NK cells in blood, which in turn correlated positively with elevated levels of cardiac troponin T. Abundance of the CD57 NK subset was particularly prominent in males and in those after the second dose of vaccination. Genotypically, killer cell immunoglobulin-like receptor (KIR) KIR2DL5B(-)/KIR2DS3(+)/KIR2DS5(-)/KIR2DS4del(+) was a risk haplotype, in addition to single-nucleotide polymorphisms related to the NK cell-specific expression quantitative trait loci DNAM-1 and FuT11, which also correlated with cardiac troponin T levels in post-vaccination patients with myocarditis. CONCLUSION: Collectively, these data suggest that NK cell activation by mRNA COVID-19 vaccine contributed to the pathogenesis of acute myocarditis in genetically and epidemiologically vulnerable subjects.
Original languageEnglish
Pages (from-to)335-347.e3
JournalMed (New York, N.Y.)
Issue number4
Early online date15 Mar 2024
Publication statusPublished - 12 Apr 2024

Bibliographical note

Copyright © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY-NC license (


  • NK cells
  • Translation to patients
  • innate immunity
  • vaccine-related myocarditis
  • hypercytokinemia
  • inflammation
  • BNT162b2 mRNA COVID-19 vaccines
  • KIR genetics


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