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SARS-CoV-2 leads to a small vessel endotheliitis in the heart.
Maccio, Umberto; Zinkernagel, Annelies S; Shambat, Srikanth Mairpady; Zeng, Xiankun; Cathomas, Gieri; Ruschitzka, Frank; Schuepbach, Reto A; Moch, Holger; Varga, Zsuzsanna.
  • Maccio U; Department of Pathology and Molecular Pathology, University Hospital Zürich, University of Zurich, Schmelzbergstrasse 12., Zurich CH-8091, Switzerland.
  • Zinkernagel AS; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zurich, Switzerland.
  • Shambat SM; Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zurich, Switzerland.
  • Zeng X; United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, United States.
  • Cathomas G; Reference Pathology for Infectious Diseases, Cantonal Hospital Liestal, Baselland, Switzerland.
  • Ruschitzka F; Department of Cardiology, University Hospital Zurich, University of Zurich, Switzerland.
  • Schuepbach RA; Institute of Intensive Care, University Hospital Zurich, University of Zurich, Switzerland.
  • Moch H; Department of Pathology and Molecular Pathology, University Hospital Zürich, University of Zurich, Schmelzbergstrasse 12., Zurich CH-8091, Switzerland.
  • Varga Z; Department of Pathology and Molecular Pathology, University Hospital Zürich, University of Zurich, Schmelzbergstrasse 12., Zurich CH-8091, Switzerland. Electronic address: zsuzsanna.varga@usz.ch.
EBioMedicine ; 63: 103182, 2021 Jan.
Article in English | MEDLINE | ID: covidwho-1014448
ABSTRACT

BACKGROUND:

SARS-CoV-2 infection (COVID-19 disease) can induce systemic vascular involvement contributing to morbidity and mortality. SARS-CoV-2 targets epithelial and endothelial cells through the ACE2 receptor. The anatomical involvement of the coronary tree is not explored yet.

METHODS:

Cardiac autopsy tissue of the entire coronary tree (main coronary arteries, epicardial arterioles/venules, epicardial capillaries) and epicardial nerves were analyzed in COVID-19 patients (n = 6). All anatomical regions were immunohistochemically tested for ACE2, TMPRSS2, CD147, CD45, CD3, CD4, CD8, CD68 and IL-6. COVID-19 negative patients with cardiovascular disease (n = 3) and influenza A (n = 6) served as controls.

FINDINGS:

COVID-19 positive patients showed strong ACE2 / TMPRSS2 expression in capillaries and less in arterioles/venules. The main coronary arteries were virtually devoid of ACE2 receptor and had only mild intimal inflammation. Epicardial capillaries had a prominent lympho-monocytic endotheliitis, which was less pronounced in arterioles/venules. The lymphocytic-monocytic infiltrate strongly expressed CD4, CD45, CD68. Peri/epicardial nerves had strong ACE2 expression and lympho-monocytic inflammation. COVID-19 negative patients showed minimal vascular ACE2 expression and lacked endotheliitis or inflammatory reaction.

INTERPRETATION:

ACE2 / TMPRSS2 expression and lymphomonocytic inflammation in COVID-19 disease increases crescentically towards the small vessels suggesting that COVID-19-induced endotheliitis is a small vessel vasculitis not involving the main coronaries. The inflammatory neuropathy of epicardial nerves in COVID-19 disease provides further evidence of an angio- and neurotrophic affinity of SARS-COV2 and might potentially contribute to the understanding of the high prevalence of cardiac complications such as myocardial injury and arrhythmias in COVID-19.

FUNDING:

No external funding was necessary for this study.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Capillaries / Coronary Vessels / SARS-CoV-2 Type of study: Observational study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: EBioMedicine Year: 2021 Document Type: Article Affiliation country: J.ebiom.2020.103182

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Capillaries / Coronary Vessels / SARS-CoV-2 Type of study: Observational study Limits: Aged / Female / Humans / Male / Middle aged Language: English Journal: EBioMedicine Year: 2021 Document Type: Article Affiliation country: J.ebiom.2020.103182