Vascular occlusion by neutrophil extracellular traps in COVID-19

Leppkes M, Knopf J, Naschberger E, Lindemann A, Singh J, Herrmann I, Stürzl M, Staats L, Mahajan A, Kremer A, Amann KU, Evert K, Falkeis C, Wehrfritz A, Rieker R, Hartmann A, Kremer A, Neurath M, Munoz LE, Schett G, Herrmann M, Völkl S, Schauer C (2020)

Publication Type: Journal article

Publication year: 2020

Journal

EBioMedicine Elsevier

Book Volume: 58

Article Number: 102925

DOI: 10.1016/j.ebiom.2020.102925

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

Authors with CRIS profile

Jasmin Knopf Department of Medicine 3 – Rheumatology and Immunology Elisabeth Naschberger Medizinische Fakultät Jeeshan Singh Department of Medicine 3 – Rheumatology and Immunology Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie Aparna Mahajan Department of Medicine 3 – Rheumatology and Immunology Anita Kremer Department of Medicine 5 – Haematology and Oncology Kerstin Ute Amann Professur für Nephropathologie Ralf Rieker Institute of Pathology Arndt Hartmann Lehrstuhl für Allgemeine Pathologie und Pathologische Anatomie Andreas Kremer Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Markus Neurath Lehrstuhl für Innere Medizin I Luis Munoz Becerra Department of Medicine 3 – Rheumatology and Immunology Georg Schett Lehrstuhl für Innere Medizin III Martin Herrmann Department of Medicine 3 – Rheumatology and Immunology Simon Völkl Department of Medicine 5 – Haematology and Oncology Christine Schauer Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

Klinikum Bayreuth DE Germany (DE) Universitätsklinikum Regensburg DE Germany (DE)

How to cite

APA:

Leppkes, M., Knopf, J., Naschberger, E., Lindemann, A., Singh, J., Herrmann, I.,... Schauer, C. (2020). Vascular occlusion by neutrophil extracellular traps in COVID-19. EBioMedicine, 58. https://doi.org/10.1016/j.ebiom.2020.102925

MLA:

Leppkes, Moritz, et al. "Vascular occlusion by neutrophil extracellular traps in COVID-19." EBioMedicine 58 (2020).

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