The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies

RationaleMyocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide.ObjectiveThis histological and immunohisto...

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Autores principales:	Camila Hartmann, Anna Flavia Ribeiro dos Santos Miggiolaro, Jarbas da Silva Motta, Lucas Baena Carstens, Caroline Busatta Vaz De Paula, Sarah Fagundes Grobe, Larissa Hermann de Souza Nunes, Gustavo Lenci Marques, Peter Libby, Lidia Zytynski Moura, Lucia de Noronha, Cristina Pellegrino Baena
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	heart myocardial injury COVID-19 SARS-CoV-2 endothelium immunohistochemistry Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/0d7c7858a6364933ba716da9b8470f5b
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spelling	oai:doaj.org-article:0d7c7858a6364933ba716da9b8470f5b2021-11-05T12:16:21ZThe Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies1664-322410.3389/fimmu.2021.748417https://doaj.org/article/0d7c7858a6364933ba716da9b8470f5b2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.748417/fullhttps://doaj.org/toc/1664-3224RationaleMyocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide.ObjectiveThis histological and immunohistochemical study sought to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury.Methods and ResultsPostmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control group (n=11). Histological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: caspase-1, caspase-9, gasdermin-d, ICAM-1, IL-1β, IL-4, IL-6, CD163, TNF-α, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also assessed for apoptotic cells by TUNEL. Histological analysis showed severe pericardiocyte interstitial edema and higher mast cells counts per high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-1β, IL-6, MMP-9, TNF-α, and other markers in the hearts of COVID-19 patients. Expression of caspase-9 did not differ from the controls, while gasdermin-d expression was less. The TUNEL assay was positive in all the COVID-19 samples supporting endothelial apoptosis.ConclusionsThe pathogenesis of COVID-19 myocardial injury does not seem to relate to primary myocardiocyte involvement but to local inflammation with associated interstitial edema. We found heightened TGF-β and interstitial collagen expression in COVID-affected hearts, a potential harbinger of chronic myocardial fibrosis. These results suggest a need for continued clinical surveillance of patients for myocardial dysfunction and arrythmias after recovery from the acute phase of COVID-19.Camila HartmannCamila HartmannAnna Flavia Ribeiro dos Santos MiggiolaroAnna Flavia Ribeiro dos Santos MiggiolaroJarbas da Silva MottaLucas Baena CarstensCaroline Busatta Vaz De PaulaSarah Fagundes GrobeSarah Fagundes GrobeLarissa Hermann de Souza NunesLarissa Hermann de Souza NunesGustavo Lenci MarquesGustavo Lenci MarquesPeter LibbyLidia Zytynski MouraLidia Zytynski MouraLucia de NoronhaCristina Pellegrino BaenaCristina Pellegrino BaenaFrontiers Media S.A.articleheartmyocardial injuryCOVID-19SARS-CoV-2endotheliumimmunohistochemistryImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	heart myocardial injury COVID-19 SARS-CoV-2 endothelium immunohistochemistry Immunologic diseases. Allergy RC581-607
spellingShingle	heart myocardial injury COVID-19 SARS-CoV-2 endothelium immunohistochemistry Immunologic diseases. Allergy RC581-607 Camila Hartmann Camila Hartmann Anna Flavia Ribeiro dos Santos Miggiolaro Anna Flavia Ribeiro dos Santos Miggiolaro Jarbas da Silva Motta Lucas Baena Carstens Caroline Busatta Vaz De Paula Sarah Fagundes Grobe Sarah Fagundes Grobe Larissa Hermann de Souza Nunes Larissa Hermann de Souza Nunes Gustavo Lenci Marques Gustavo Lenci Marques Peter Libby Lidia Zytynski Moura Lidia Zytynski Moura Lucia de Noronha Cristina Pellegrino Baena Cristina Pellegrino Baena The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies
description	RationaleMyocardial injury associates significantly and independently with mortality in COVID-19 patients. However, the pathogenesis of myocardial injury in COVID-19 remains unclear, and cardiac involvement by SARS-CoV-2 presents a major challenge worldwide.ObjectiveThis histological and immunohistochemical study sought to clarify the pathogenesis and propose a mechanism with pathways involved in COVID-19 myocardial injury.Methods and ResultsPostmortem minimally invasive autopsies were performed in six patients who died from COVID-19, and the myocardium samples were compared to a control group (n=11). Histological analysis was performed using hematoxylin-eosin and toluidine blue staining. Immunohistochemical (IHC) staining was performed using monoclonal antibodies against targets: caspase-1, caspase-9, gasdermin-d, ICAM-1, IL-1β, IL-4, IL-6, CD163, TNF-α, TGF-β, MMP-9, type 1 and type 3 collagen. The samples were also assessed for apoptotic cells by TUNEL. Histological analysis showed severe pericardiocyte interstitial edema and higher mast cells counts per high-power field in all COVID-19 myocardium samples. The IHC analysis showed increased expression of caspase-1, ICAM-1, IL-1β, IL-6, MMP-9, TNF-α, and other markers in the hearts of COVID-19 patients. Expression of caspase-9 did not differ from the controls, while gasdermin-d expression was less. The TUNEL assay was positive in all the COVID-19 samples supporting endothelial apoptosis.ConclusionsThe pathogenesis of COVID-19 myocardial injury does not seem to relate to primary myocardiocyte involvement but to local inflammation with associated interstitial edema. We found heightened TGF-β and interstitial collagen expression in COVID-affected hearts, a potential harbinger of chronic myocardial fibrosis. These results suggest a need for continued clinical surveillance of patients for myocardial dysfunction and arrythmias after recovery from the acute phase of COVID-19.
format	article
author	Camila Hartmann Camila Hartmann Anna Flavia Ribeiro dos Santos Miggiolaro Anna Flavia Ribeiro dos Santos Miggiolaro Jarbas da Silva Motta Lucas Baena Carstens Caroline Busatta Vaz De Paula Sarah Fagundes Grobe Sarah Fagundes Grobe Larissa Hermann de Souza Nunes Larissa Hermann de Souza Nunes Gustavo Lenci Marques Gustavo Lenci Marques Peter Libby Lidia Zytynski Moura Lidia Zytynski Moura Lucia de Noronha Cristina Pellegrino Baena Cristina Pellegrino Baena
author_facet	Camila Hartmann Camila Hartmann Anna Flavia Ribeiro dos Santos Miggiolaro Anna Flavia Ribeiro dos Santos Miggiolaro Jarbas da Silva Motta Lucas Baena Carstens Caroline Busatta Vaz De Paula Sarah Fagundes Grobe Sarah Fagundes Grobe Larissa Hermann de Souza Nunes Larissa Hermann de Souza Nunes Gustavo Lenci Marques Gustavo Lenci Marques Peter Libby Lidia Zytynski Moura Lidia Zytynski Moura Lucia de Noronha Cristina Pellegrino Baena Cristina Pellegrino Baena
author_sort	Camila Hartmann
title	The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies
title_short	The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies
title_full	The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies
title_fullStr	The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies
title_full_unstemmed	The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies
title_sort	pathogenesis of covid-19 myocardial injury: an immunohistochemical study of postmortem biopsies
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/0d7c7858a6364933ba716da9b8470f5b
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The Pathogenesis of COVID-19 Myocardial Injury: An Immunohistochemical Study of Postmortem Biopsies

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