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SARS-CoV-2 leads to a small vessel endotheliitis in the heart.
EBioMedicine. 2021 Jan; 63:103182.E

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.

Authors+Show Affiliations

Department of Pathology and Molecular Pathology, University Hospital Zürich, University of Zurich, Schmelzbergstrasse 12., Zurich CH-8091, Switzerland.Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zurich, Switzerland.Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zurich, Switzerland.United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD, United States.Reference Pathology for Infectious Diseases, Cantonal Hospital Liestal, Baselland, Switzerland.Department of Cardiology, University Hospital Zurich, University of Zurich, Switzerland.Institute of Intensive Care, University Hospital Zurich, University of Zurich, Switzerland.Department of Pathology and Molecular Pathology, University Hospital Zürich, University of Zurich, Schmelzbergstrasse 12., Zurich CH-8091, Switzerland.Department of Pathology and Molecular Pathology, University Hospital Zürich, University of Zurich, Schmelzbergstrasse 12., Zurich CH-8091, Switzerland. Electronic address: zsuzsanna.varga@usz.ch.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33422990

Citation

Maccio, Umberto, et al. "SARS-CoV-2 Leads to a Small Vessel Endotheliitis in the Heart." EBioMedicine, vol. 63, 2021, p. 103182.
Maccio U, Zinkernagel AS, Shambat SM, et al. SARS-CoV-2 leads to a small vessel endotheliitis in the heart. EBioMedicine. 2021;63:103182.
Maccio, U., Zinkernagel, A. S., Shambat, S. M., Zeng, X., Cathomas, G., Ruschitzka, F., Schuepbach, R. A., Moch, H., & Varga, Z. (2021). SARS-CoV-2 leads to a small vessel endotheliitis in the heart. EBioMedicine, 63, 103182. https://doi.org/10.1016/j.ebiom.2020.103182
Maccio U, et al. SARS-CoV-2 Leads to a Small Vessel Endotheliitis in the Heart. EBioMedicine. 2021;63:103182. PubMed PMID: 33422990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 leads to a small vessel endotheliitis in the heart. AU - Maccio,Umberto, AU - Zinkernagel,Annelies S, AU - Shambat,Srikanth Mairpady, AU - Zeng,Xiankun, AU - Cathomas,Gieri, AU - Ruschitzka,Frank, AU - Schuepbach,Reto A, AU - Moch,Holger, AU - Varga,Zsuzsanna, Y1 - 2021/01/07/ PY - 2020/09/21/received PY - 2020/12/02/revised PY - 2020/12/07/accepted PY - 2021/1/11/pubmed PY - 2021/1/29/medline PY - 2021/1/10/entrez KW - ACE2-receptor KW - COVID-19 KW - Coronary arteries KW - Endothelial dysfunction KW - Epicardial capillaries KW - Epicardial nerves KW - Microangiopathy SP - 103182 EP - 103182 JF - EBioMedicine JO - EBioMedicine VL - 63 N2 - 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. SN - 2352-3964 UR - https://www.unboundmedicine.com/medline/citation/33422990/SARS_CoV_2_leads_to_a_small_vessel_endotheliitis_in_the_heart_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2352-3964(20)30558-2 DB - PRIME DP - Unbound Medicine ER -