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Case Reports
. 2021 Dec 9:12:779026.
doi: 10.3389/fimmu.2021.779026. eCollection 2021.

Evidence of SARS-CoV-2-Specific T-Cell-Mediated Myocarditis in a MIS-A Case

Kevin M Vannella  1   2 , Cihan Oguz  3   4 , Sydney R Stein  1   2 , Stefania Pittaluga  5 , Esra Dikoglu  5 , Arjun Kanwal  6 , Sabrina C Ramelli  7 , Thomas Briese  8 , Ling Su  9 , Xiaolin Wu  9 , Marcos J Ramos-Benitez  1   2   10 , Luis J Perez-Valencia  1   2 , Ashley Babyak  1   2 , Nu Ri Cha  11 , Joon-Yong Chung  5 , Kris Ylaya  5 , Ronson J Madathil  12 , Kapil K Saharia  13 , Thomas M Scalea  14 , Quincy K Tran  15 , Daniel L Herr  16 , David E Kleiner  5 , Stephen M Hewitt  5 , Luigi D Notarangelo  17 , Alison Grazioli  18 , Daniel S Chertow  1   2
Affiliations
Case Reports

Evidence of SARS-CoV-2-Specific T-Cell-Mediated Myocarditis in a MIS-A Case

Kevin M Vannella et al. Front Immunol. .

Abstract

A 26-year-old otherwise healthy man died of fulminant myocarditis. Nasopharyngeal specimens collected premortem tested negative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Histopathological evaluation of the heart showed myocardial necrosis surrounded by cytotoxic T-cells and tissue-repair macrophages. Myocardial T-cell receptor (TCR) sequencing revealed hyper-dominant clones with highly similar sequences to TCRs that are specific for SARS-CoV-2 epitopes. SARS-CoV-2 RNA was detected in the gut, supporting a diagnosis of multisystem inflammatory syndrome in adults (MIS-A). Molecular targets of MIS-associated inflammation are not known. Our data indicate that SARS-CoV-2 antigens selected high-frequency T-cell clones that mediated fatal myocarditis.

Keywords: CDR3 sequences; MIS-A; SARS-CoV-2; SARS-CoV-2 epitopes; T cell receptor (TCR); cd-hit; myocarditis.

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Conflict of interest statement

Authors CO, LS and XW were employed by company Leidos Biomedical Research, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Histopathology images of myocardium. (A) H&E section from the myocardium shows contraction band myocyte necrosis (arrows) (40x). (B) H&E section from the myocardium shows an inflammatory infiltrate mostly composed of lymphocytes and macrophages (arrows) (10x) as seen better in (C) by an immunohistochemical stain for CD3, which marks T lymphocytes (10x). (D) A double immunohistochemical stain highlights the presence of CD8-positive T cells (red chromogen) and CD4-positive T cells (brown chromogen); low grade expression by CD4 marks macrophages (40x); (E, F) show the presence of scattered cytotoxic T cells positive for perforin (40X) and granzyme B (40X), respectively. (G, H) Presence of numerous histiocytes/macrophages is confirmed by CD68 (10x) and CD163 (10x) staining, respectively.
Figure 2
Figure 2
Characterization of T cell clonotype abundance in cardiac tissues alongside lung and lymph node for comparison. (A) T cell repertoire overlap across tissues using Morisita indices (1&red=highest; 0&blue=lowest). (B) Percentage of T cell clonotypes with small (0-0.001, orange); medium (0.001-0.01, tan); large (0.01-0.1; light blue); and hyperexpanded (0.1-1; dark blue) frequencies across tissues. NA, Not applicable.
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