• Moritz Leppkes, Jasmin Knopf, Elisabeth Naschberger, Aylin Lindemann, Jeeshan Singh, Irmgard Herrmann, Michael Stürzl, Léonie Staats, Aparna Mahajan, Christine Schauer, Anita N Kremer, Simon Völkl, Kerstin Amann, Katja Evert, Christina Falkeis, Andreas Wehrfritz, Ralf J Rieker, Arndt Hartmann, Andreas E Kremer, Markus F Neurath, Luis E Muñoz, Georg Schett, and Martin Herrmann.
• Department of Internal Medicine 1, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany. Electronic address: moritz.leppkes@uk-erlangen.de.
• EBioMedicine. 2020 Aug 1; 58: 102925.

BackgroundCoronavirus 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.MethodsSamples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry.Patient FindingsHere, 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.InterpretationThese data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage.FundingDeutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung.Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

32 keywords...

hide…