Frontiers in Immunology (Dec 2021)
Evidence of SARS-CoV-2-Specific T-Cell-Mediated Myocarditis in a MIS-A Case
- Kevin M. Vannella,
- Kevin M. Vannella,
- Cihan Oguz,
- Cihan Oguz,
- Sydney R. Stein,
- Sydney R. Stein,
- Stefania Pittaluga,
- Esra Dikoglu,
- Arjun Kanwal,
- Sabrina C. Ramelli,
- Thomas Briese,
- Ling Su,
- Xiaolin Wu,
- Marcos J. Ramos-Benitez,
- Marcos J. Ramos-Benitez,
- Marcos J. Ramos-Benitez,
- Luis J. Perez-Valencia,
- Luis J. Perez-Valencia,
- Ashley Babyak,
- 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,
- Daniel S. Chertow
Affiliations
- Kevin M. Vannella
- Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Kevin M. Vannella
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Cihan Oguz
- National Institute of Allergy and Infectious Diseases Collaborative Bioinformatics Resource, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, United States
- Cihan Oguz
- Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, United States
- Sydney R. Stein
- Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Sydney R. Stein
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Stefania Pittaluga
- Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
- Esra Dikoglu
- Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
- Arjun Kanwal
- Division of Cardiology, Westchester Medical Center, Valhalla, NY, United States
- Sabrina C. Ramelli
- Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Thomas Briese
- Center for Infection and Immunity, Columbia University Mailman School of Public Health, New York, NY, United States
- Ling Su
- Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, United States
- Xiaolin Wu
- Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD, United States
- Marcos J. Ramos-Benitez
- Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Marcos J. Ramos-Benitez
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Marcos J. Ramos-Benitez
- 0Postdoctoral Research Associate Training Program, National Institute of General Medical Sciences, National Institutes of Health, Bethesda, MD, United States
- Luis J. Perez-Valencia
- Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Luis J. Perez-Valencia
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Ashley Babyak
- Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Ashley Babyak
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Nu Ri Cha
- 1Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Joon-Yong Chung
- Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
- Kris Ylaya
- Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
- Ronson J. Madathil
- 2Department of Surgery, Division of Cardiac Surgery, University of Maryland School of Medicine, Baltimore, MD, United States
- Kapil K. Saharia
- 3Department of Medicine, Division of Infectious Disease, University of Maryland School of Medicine, Baltimore, MD, United States
- Thomas M. Scalea
- 4Department of Surgery, Program in Trauma, R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, United States
- Quincy K. Tran
- 5Department of Emergency Medicine, R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, United States
- Daniel L. Herr
- 6Department of Medicine, Program in Trauma, R. Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD, United States
- David E. Kleiner
- Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
- Stephen M. Hewitt
- Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States
- Luigi D. Notarangelo
- 7Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- Alison Grazioli
- 8Kidney Diseases Branch, Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States
- Daniel S. Chertow
- Emerging Pathogens Section, Critical Care Medicine Department, Clinical Center, National Institutes of Health, Bethesda, MD, United States
- Daniel S. Chertow
- Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United States
- DOI
- https://doi.org/10.3389/fimmu.2021.779026
- Journal volume & issue
-
Vol. 12
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
