EBioMedicine . Vascular occlusion by neutrophil extracellular traps in COVID-19

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EBioMedicine


. 2020 Jul 31;58:102925.
doi: 10.1016/j.ebiom.2020.102925. Online ahead of print.
Vascular occlusion by neutrophil extracellular traps in COVID-19


Moritz Leppkes ¹ , Jasmin Knopf ² , Elisabeth Naschberger ³ , Aylin Lindemann ⁴ , Jeeshan Singh ² , Irmgard Herrmann ⁵ , Michael St?rzl ³ , L?onie Staats ⁴ , Aparna Mahajan ² , Christine Schauer ² , Anita N Kremer ⁶ , Simon V?lkl ⁶ , Kerstin Amann ⁷ , Katja Evert ⁸ , Christina Falkeis ⁹ , Andreas Wehrfritz ¹⁰ , Ralf J Rieker ¹¹ , Arndt Hartmann ¹¹ , Andreas E Kremer ⁴ , Markus F Neurath ⁴ , Luis E Mu?oz ² , Georg Schett ² , Martin Herrmann ²



Affiliations

• PMID: 32745993
• DOI: 10.1016/j.ebiom.2020.102925

Free article

Abstract

Background: 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.
Methods: Samples were donated from hospitalized patients. Sera, plasma, and autopsy-derived tissue sections were examined employing flow cytometry, enzyme-linked immunosorbent assays, and immunohistochemistry.
Patient findings: 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.
Interpretation: These data suggest that organ dysfunction in severe COVID-19 is associated with excessive NET formation and vascular damage.
Funding: Deutsche Forschungsgemeinschaft (DFG), EU, Volkswagen-Stiftung.

Keywords: Aggregated neutrophil extracellular traps; Coagulopathy; Endothelialitis; Immunothrombosis; SARS-CoV-2.