Vascular occlusion by neutrophil extracellular traps in COVID-19

Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood. Samples were donated from hospitalized patients. Sera, plasma, and autopsy-deri...

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Published in:EBioMedicine Vol. 58; p. 102925
Main Authors: Leppkes, Moritz, Knopf, Jasmin, Naschberger, Elisabeth, Lindemann, Aylin, Singh, Jeeshan, Herrmann, Irmgard, Stürzl, Michael, Staats, Léonie, Mahajan, Aparna, Schauer, Christine, Kremer, Anita N., Völkl, Simon, Amann, Kerstin, Evert, Katja, Falkeis, Christina, Wehrfritz, Andreas, Rieker, Ralf J., Hartmann, Arndt, Kremer, Andreas E., Neurath, Markus F., Muñoz, Luis E., Schett, Georg, Herrmann, Martin
Format: Journal Article
Language:English
Published: Netherlands Elsevier B.V 01.08.2020
Elsevier
Subjects:
Advanced Basic Science
Aggregated neutrophil extracellular traps
Cells, Cultured
Coagulopathy
Coronavirus Infections - complications
Coronavirus Infections - metabolism
Coronavirus Infections - pathology
COVID-19
Endothelialitis
Endothelium, Vascular - metabolism
Endothelium, Vascular - pathology
Extracellular Traps - metabolism
Humans
Immunothrombosis
Internal Medicine
Microvessels - metabolism
Microvessels - pathology
Neutrophils - metabolism
Neutrophils - pathology
Pandemics
Pneumonia, Viral - complications
Pneumonia, Viral - metabolism
Pneumonia, Viral - pathology
Research paper
SARS-CoV-2
Thrombosis - etiology
Thrombosis - metabolism
Thrombosis - pathology
Endothelialitis
SARS-CoV-2
Immunothrombosis
Aggregated neutrophil extracellular traps
Coagulopathy
ISSN:2352-3964, 2352-3964
Online Access:Get full text
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Summary:Coronavirus induced disease 2019 (COVID-19) can be complicated by severe organ damage leading to dysfunction of the lungs and other organs. The processes that trigger organ damage in COVID-19 are incompletely understood. Samples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry. Here, we show that severe COVID-19 is characterized by a highly pronounced formation of neutrophil extracellular traps (NETs) inside the micro-vessels. Intravascular aggregation of NETs leads to rapid occlusion of the affected vessels, disturbed microcirculation, and organ damage. In severe COVID-19, neutrophil granulocytes are strongly activated and adopt a so-called low-density phenotype, prone to spontaneously form NETs. In accordance, markers indicating NET turnover are consistently increased in COVID-19 and linked to disease severity. Histopathology of the lungs and other organs from COVID-19 patients showed congestions of numerous micro-vessels by aggregated NETs associated with endothelial damage. These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage. Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung
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ML and JK equally contributed
ISSN:2352-3964
2352-3964
DOI:10.1016/j.ebiom.2020.102925