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Histologic, viral, and molecular correlates of heart disease in fatal COVID-19
Cardiac manifestations are common in severe COVID-19. This study compared the histologic, viral, and molecular findings in cardiac tissue in fatal COVID-19 (n = 11) and controls (n = 11). In situ hybridization (SARS-CoV2 RNA) and immunohistochemistry for viral proteins and the host response were qua...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148434/ https://www.ncbi.nlm.nih.gov/pubmed/35660807 http://dx.doi.org/10.1016/j.anndiagpath.2022.151983 |
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author | Mezache, Louisa Nuovo, Gerard J. Suster, David Tili, Esmerina Awad, Hamdy Radwański, Przemysław B. Veeraraghavan, Rengasayee |
author_facet | Mezache, Louisa Nuovo, Gerard J. Suster, David Tili, Esmerina Awad, Hamdy Radwański, Przemysław B. Veeraraghavan, Rengasayee |
author_sort | Mezache, Louisa |
collection | PubMed |
description | Cardiac manifestations are common in severe COVID-19. This study compared the histologic, viral, and molecular findings in cardiac tissue in fatal COVID-19 (n = 11) and controls (n = 11). In situ hybridization (SARS-CoV2 RNA) and immunohistochemistry for viral proteins and the host response were quantified for the samples and compared with qRTPCR and Western blot data. Control hearts showed a high resident population of macrophages that had variable ACE2 expression. Cardiac ACE2 expression was 10× greater in the heart tissues of cases and controls with obesity or type II diabetes. Multifocal endothelial cell swelling and degeneration, perivascular edema plus microvascular thrombi were unique to the cases. SARS-CoV2 RNA and nucleocapsid protein were rarely detected in situ in any COVID-19 heart. However, in each case abundant SARS-CoV-2 spike protein was evident. Co-expression experiments showed that the spike protein localized mostly to the ACE2+ interstitial macrophages/pericytes that were activated as evidenced by increased IL6 and TNFα expression. Western blots confirmed the presence of the viral spike protein, but not the nucleocapsid protein, in the cardiac homogenates. The intercalated disc proteins connexin 43, the primary cardiac gap junction protein, and Na(V)1.5, the predominant cardiac sodium channel, each showed marked lateral migration in the myocytes in the cases, which would increase the risk of reentrant arrhythmias. It is concluded that the viral spike protein, endocytosed by macrophages/pericytes, can induce a myocarditis with the possibility of conduction dysfunction due to abnormal localization of key intercalated disc proteins. |
format | Online Article Text |
id | pubmed-9148434 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91484342022-05-31 Histologic, viral, and molecular correlates of heart disease in fatal COVID-19 Mezache, Louisa Nuovo, Gerard J. Suster, David Tili, Esmerina Awad, Hamdy Radwański, Przemysław B. Veeraraghavan, Rengasayee Ann Diagn Pathol Original Contribution Cardiac manifestations are common in severe COVID-19. This study compared the histologic, viral, and molecular findings in cardiac tissue in fatal COVID-19 (n = 11) and controls (n = 11). In situ hybridization (SARS-CoV2 RNA) and immunohistochemistry for viral proteins and the host response were quantified for the samples and compared with qRTPCR and Western blot data. Control hearts showed a high resident population of macrophages that had variable ACE2 expression. Cardiac ACE2 expression was 10× greater in the heart tissues of cases and controls with obesity or type II diabetes. Multifocal endothelial cell swelling and degeneration, perivascular edema plus microvascular thrombi were unique to the cases. SARS-CoV2 RNA and nucleocapsid protein were rarely detected in situ in any COVID-19 heart. However, in each case abundant SARS-CoV-2 spike protein was evident. Co-expression experiments showed that the spike protein localized mostly to the ACE2+ interstitial macrophages/pericytes that were activated as evidenced by increased IL6 and TNFα expression. Western blots confirmed the presence of the viral spike protein, but not the nucleocapsid protein, in the cardiac homogenates. The intercalated disc proteins connexin 43, the primary cardiac gap junction protein, and Na(V)1.5, the predominant cardiac sodium channel, each showed marked lateral migration in the myocytes in the cases, which would increase the risk of reentrant arrhythmias. It is concluded that the viral spike protein, endocytosed by macrophages/pericytes, can induce a myocarditis with the possibility of conduction dysfunction due to abnormal localization of key intercalated disc proteins. Elsevier Inc. 2022-10 2022-05-29 /pmc/articles/PMC9148434/ /pubmed/35660807 http://dx.doi.org/10.1016/j.anndiagpath.2022.151983 Text en © 2022 Elsevier Inc. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. |
spellingShingle | Original Contribution Mezache, Louisa Nuovo, Gerard J. Suster, David Tili, Esmerina Awad, Hamdy Radwański, Przemysław B. Veeraraghavan, Rengasayee Histologic, viral, and molecular correlates of heart disease in fatal COVID-19 |
title | Histologic, viral, and molecular correlates of heart disease in fatal COVID-19 |
title_full | Histologic, viral, and molecular correlates of heart disease in fatal COVID-19 |
title_fullStr | Histologic, viral, and molecular correlates of heart disease in fatal COVID-19 |
title_full_unstemmed | Histologic, viral, and molecular correlates of heart disease in fatal COVID-19 |
title_short | Histologic, viral, and molecular correlates of heart disease in fatal COVID-19 |
title_sort | histologic, viral, and molecular correlates of heart disease in fatal covid-19 |
topic | Original Contribution |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148434/ https://www.ncbi.nlm.nih.gov/pubmed/35660807 http://dx.doi.org/10.1016/j.anndiagpath.2022.151983 |
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