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Single-cell sequencing of PBMC characterizes the altered transcriptomic landscape of classical monocytes in BNT162b2-induced myocarditis.

Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been the most dangerous threat to public health worldwide for the last few years, which led to the development of the novel mRNA vaccine (BNT162b2). However, BNT162b2 vaccination is known to be associated with myocarditis. Here, as an attempt to determine the pathogenesis of the disease and to develop biomarkers to determine whether subjects likely proceed to myocarditis after vaccination, we conducted a time series analysis of peripheral blood mononuclear cells of a patient with BNT162b2-induced myocarditis. Single-cell RNA sequence analysis identified monocytes as the cell clusters with the most dynamic changes. To identify distinct gene expression signatures, we compared monocytes of BNT162b2-induced myocarditis with monocytes under various conditions, including SARS-CoV-2 infection, BNT162b2 vaccination, and Kawasaki disease, a disease similar to myocarditis. Representative changes in the transcriptomic profile of classical monocytes include the upregulation of genes related to fatty acid metabolism and downregulation of transcription factor AP-1 activity. This study provides, for the first time, the importance of classical monocytes in the pathogenesis of myocarditis following BNT162b2 vaccination and presents the possibility that vaccination affects monocytes, further inducing their differentiation and infiltration into the heart.
AuthorsNahee Hwang, Yune Huh, Seonghyeon Bu, Kyung Jin Seo, Se Hwan Kwon, Jae-Woo Kim, Bo Kyung Yoon, Hyo-Suk Ahn, Sungsoon Fang
JournalFrontiers in immunology (Front Immunol) Vol. 13 Pg. 979188 ( 2022) ISSN: 1664-3224 [Electronic] Switzerland
PMID36225942 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2022 Hwang, Huh, Bu, Seo, Kwon, Kim, Yoon, Ahn and Fang.
Chemical References
  • Fatty Acids
  • Transcription Factor AP-1
  • Vaccines, Synthetic
  • mRNA Vaccine
  • mRNA Vaccines
  • BNT162 Vaccine
Topics
  • BNT162 Vaccine
  • COVID-19
  • Fatty Acids
  • Humans
  • Leukocytes, Mononuclear
  • Monocytes
  • Myocarditis (genetics)
  • SARS-CoV-2
  • Transcription Factor AP-1
  • Transcriptome
  • Vaccines, Synthetic
  • mRNA Vaccines

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