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

Kevin M Vannella; Cihan Oguz; Sydney R Stein; Stefania Pittaluga; Esra Dikoglu; Arjun Kanwal; Sabrina C Ramelli; Thomas Briese; Ling Su; Xiaolin Wu; Marcos J Ramos-Benitez; Luis J Perez-Valencia; Ashley Babyak; Nu Ri Cha; Joon-Yong Chung; Kris Ylaya; Ronson J Madathil; Kapil K Saharia; Thomas M Scalea; Quincy K Tran; Daniel L Herr; David E Kleiner; Stephen M Hewitt; Luigi D Notarangelo; Alison Grazioli; Daniel S Chertow

doi:10.3389/fimmu.2021.779026

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

Front Immunol. 2021 Dec 9:12:779026. doi: 10.3389/fimmu.2021.779026. eCollection 2021.

Authors

Kevin M Vannella^{1

2}, Cihan Oguz^{3

4}, Sydney R Stein^{1

2}, Stefania Pittaluga⁵, Esra Dikoglu⁵, Arjun Kanwal⁶, Sabrina C Ramelli⁷, Thomas Briese⁸, Ling Su⁹, Xiaolin Wu⁹, Marcos J Ramos-Benitez^{1

2

10}, Luis J Perez-Valencia^{1

2}, Ashley Babyak^{1

2}, Nu Ri Cha¹¹, Joon-Yong Chung⁵, Kris Ylaya⁵, Ronson J Madathil¹², Kapil K Saharia¹³, Thomas M Scalea¹⁴, Quincy K Tran¹⁵, Daniel L Herr¹⁶, David E Kleiner⁵, Stephen M Hewitt⁵, Luigi D Notarangelo¹⁷, Alison Grazioli¹⁸, Daniel S Chertow^{1

2}

Affiliations

¹ Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States.
² Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
³ National Institute of Allergy and Infectious Diseases Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, United States.
⁴ Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, United States.
⁵ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States.
⁶ Division of Cardiology, Westchester Medical Center, Valhalla, NY, United States.
⁷ Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States.
⁸ Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, United States.
⁹ Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, United States.
¹⁰ Postdoctoral Research Associate Training Program, National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD, United States.
¹¹ Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States.
¹² Department of Surgery, Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, MD, United States.
¹³ Department of Medicine, Division of Infectious Disease, University of Maryland School of Medicine, Baltimore, MD, United States.
¹⁴ Department of Surgery, Program in Trauma, R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, United States.
¹⁵ Department of Emergency Medicine, R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, United States.
¹⁶ Department of Medicine, Program in Trauma, R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, United States.
¹⁷ Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States.
¹⁸ Kidney Diseases Branch, Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.

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.

Copyright © 2021 Vannella, Oguz, Stein, Pittaluga, Dikoglu, Kanwal, Ramelli, Briese, Su, Wu, Ramos-Benitez, Perez-Valencia, Babyak, Cha, Chung, Ylaya, Madathil, Saharia, Scalea, Tran, Herr, Kleiner, Hewitt, Notarangelo, Grazioli and Chertow.

Publication types

Case Reports
Research Support, N.I.H., Intramural

MeSH terms

Adult
COVID-19 / complications*
COVID-19 / immunology
COVID-19 / pathology
Humans
Male
Myocarditis / immunology
Myocarditis / pathology*
Myocarditis / virology*
RNA, Viral / analysis
SARS-CoV-2
Systemic Inflammatory Response Syndrome / immunology
Systemic Inflammatory Response Syndrome / pathology*
T-Lymphocytes / immunology*

Substances

RNA, Viral

Supplementary concepts

adult multisystem inflammatory disease, COVID-19 related