4.8 Article

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

Journal

FRONTIERS IN IMMUNOLOGY
Volume 13, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2022.979188

Keywords

Coronavirus; COVID-19; single-cell RNA sequencing; monocyte; macrophage; vaccination; BNT162b2; myocarditis; transcriptome (RNA-seq)

Categories

Funding

  1. National Research Foundation from Ministry of Science and ICT [NRF-2021R1A2C2009749, NRF-2018R1A5A2025079]
  2. Korea Health Technology RD Project [HR18C0012]

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This study conducted a time series analysis of peripheral blood mononuclear cells from a patient with BNT162b2-induced myocarditis, and found the importance of classical monocytes in the pathogenesis of myocarditis. The study also suggests that vaccination may affect monocytes and induce their infiltration into the heart.
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.

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