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Inflammation and vascular remodeling in COVID-19 hearts.
Werlein, Christopher; Ackermann, Maximilian; Stark, Helge; Shah, Harshit R; Tzankov, Alexandar; Haslbauer, Jasmin Dinonne; von Stillfried, Saskia; Bülow, Roman David; El-Armouche, Ali; Kuenzel, Stephan; Robertus, Jan Lukas; Reichardt, Marius; Haverich, Axel; Höfer, Anne; Neubert, Lavinia; Plucinski, Edith; Braubach, Peter; Verleden, Stijn; Salditt, Tim; Marx, Nikolaus; Welte, Tobias; Bauersachs, Johann; Kreipe, Hans-Heinrich; Mentzer, Steven J; Boor, Peter; Black, Stephen M; Länger, Florian; Kuehnel, Mark; Jonigk, Danny.
  • Werlein C; Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
  • Ackermann M; Institute of Pathology and Department of Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke, Wuppertal, Germany.
  • Stark H; Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany.
  • Shah HR; Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
  • Tzankov A; Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
  • Haslbauer JD; Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
  • von Stillfried S; Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
  • Bülow RD; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • El-Armouche A; Institute of Medical Genetics and Pathology, University Hospital Basel, Basel, Switzerland.
  • Kuenzel S; Institute of Pathology, RWTH University of Aachen, Aachen, Germany.
  • Robertus JL; Institute of Pathology, RWTH University of Aachen, Aachen, Germany.
  • Reichardt M; Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
  • Haverich A; Institute of Pharmacology and Toxicology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
  • Höfer A; Department of Dermatology, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
  • Neubert L; Department of Histopathology, Royal Brompton and Harefield NHS Foundation Trust, London, UK.
  • Plucinski E; Institute for X-Ray Physics, University of Göttingen, Göttingen, Germany.
  • Braubach P; Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
  • Verleden S; Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
  • Salditt T; Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
  • Marx N; Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
  • Welte T; Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
  • Bauersachs J; Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
  • Kreipe HH; Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
  • Mentzer SJ; Institute of Pathology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.
  • Boor P; Member of the German Center for Lung Research (DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Hannover, Germany.
  • Black SM; Department of Thoracic Medicine, Antwerp University Hospital, Antwerp, Belgium.
  • Länger F; Institute for X-Ray Physics, University of Göttingen, Göttingen, Germany.
  • Kuehnel M; Cluster of Excellence 'Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells' (MBExC), University of Göttingen, Göttingen, Germany.
  • Jonigk D; Department of Internal Medicine I, University Hospital Aachen, Aachen, Germany.
Angiogenesis ; 2022 Nov 12.
Article in English | MEDLINE | ID: covidwho-2305635
ABSTRACT
A wide range of cardiac symptoms have been observed in COVID-19 patients, often significantly influencing the clinical outcome. While the pathophysiology of pulmonary COVID-19 manifestation has been substantially unraveled, the underlying pathomechanisms of cardiac involvement in COVID-19 are largely unknown. In this multicentre study, we performed a comprehensive analysis of heart samples from 24 autopsies with confirmed SARS-CoV-2 infection and compared them to samples of age-matched Influenza H1N1 A (n = 16), lymphocytic non-influenza myocarditis cases (n = 8), and non-inflamed heart tissue (n = 9). We employed conventional histopathology, multiplexed immunohistochemistry (MPX), microvascular corrosion casting, scanning electron microscopy, X-ray phase-contrast tomography using synchrotron radiation, and direct multiplexed measurements of gene expression, to assess morphological and molecular changes holistically. Based on histopathology, none of the COVID-19 samples fulfilled the established diagnostic criteria of viral myocarditis. However, quantification via MPX showed a significant increase in perivascular CD11b/TIE2 + -macrophages in COVID-19 over time, which was not observed in influenza or non-SARS-CoV-2 viral myocarditis patients. Ultrastructurally, a significant increase in intussusceptive angiogenesis as well as multifocal thrombi, inapparent in conventional morphological analysis, could be demonstrated. In line with this, on a molecular level, COVID-19 hearts displayed a distinct expression pattern of genes primarily coding for factors involved in angiogenesis and epithelial-mesenchymal transition (EMT), changes not seen in any of the other patient groups. We conclude that cardiac involvement in COVID-19 is an angiocentric macrophage-driven inflammatory process, distinct from classical anti-viral inflammatory responses, and substantially underappreciated by conventional histopathologic analysis. For the first time, we have observed intussusceptive angiogenesis in cardiac tissue, which we previously identified as the linchpin of vascular remodeling in COVID-19 pneumonia, as a pathognomic sign in affected hearts. Moreover, we identified CD11b + /TIE2 + macrophages as the drivers of intussusceptive angiogenesis and set forward a putative model for the molecular regulation of vascular alterations.
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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Language: English Journal subject: Hematology Year: 2022 Document Type: Article Affiliation country: S10456-022-09860-7

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Full text: Available Collection: International databases Database: MEDLINE Type of study: Experimental Studies / Prognostic study / Randomized controlled trials Language: English Journal subject: Hematology Year: 2022 Document Type: Article Affiliation country: S10456-022-09860-7