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Vascular occlusion by neutrophil extracellular traps in COVID-19.
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.
  • Leppkes M; 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.
  • Knopf J; Department of Internal Medicine 3, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Naschberger E; Division of Molecular and Experimental Surgery, Translational Research Center, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Lindemann A; Department of Internal Medicine 1, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Singh J; Department of Internal Medicine 3, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Herrmann I; Department of Internal Medicine 3, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Stürzl M; Division of Molecular and Experimental Surgery, Translational Research Center, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany.
  • Staats L; Department of Internal Medicine 1, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Mahajan A; Department of Internal Medicine 3, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Schauer C; Department of Internal Medicine 3, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Kremer AN; Department of Internal Medicine 5, Hematology and Oncology, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Völkl S; Department of Internal Medicine 5, Hematology and Oncology, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Amann K; Department of Nephropathology, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Evert K; Institute of Pathology, University Medical Center Regensburg, Germany.
  • Falkeis C; Institut of Pathology, Klinikum Bayreuth, Germany.
  • Wehrfritz A; Department of Anaesthesiology, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Rieker RJ; Institute of Pathology, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Hartmann A; Institute of Pathology, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany.
  • Kremer AE; Department of Internal Medicine 1, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Neurath MF; Department of Internal Medicine 1, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Muñoz LE; Department of Internal Medicine 3, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Schett G; Department of Internal Medicine 3, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
  • Herrmann M; Department of Internal Medicine 3, University Medical Center Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany; Deutsches Zentrum Immuntherapie (DZI), Erlangen, Germany.
EBioMedicine ; 58: 102925, 2020 Aug.
Article in English | MEDLINE | ID: covidwho-701831
Semantic information from SemMedBD (by NLM)
1. Vascular occlusion COEXISTS_WITH COVID-19
Subject
Vascular occlusion
Predicate
COEXISTS_WITH
Object
COVID-19
2. Postmortem tissue sample LOCATION_OF Transection (procedure)
Subject
Postmortem tissue sample
Predicate
LOCATION_OF
Object
Transection (procedure)
3. Blood Vessel LOCATION_OF COVID-19
Subject
Blood Vessel
Predicate
LOCATION_OF
Object
COVID-19
4. Blood Vessel LOCATION_OF Complete obstruction
Subject
Blood Vessel
Predicate
LOCATION_OF
Object
Complete obstruction
5. Blood Vessel LOCATION_OF Congestion
Subject
Blood Vessel
Predicate
LOCATION_OF
Object
Congestion
6. Single organ dysfunction ASSOCIATED_WITH COVID-19
Subject
Single organ dysfunction
Predicate
ASSOCIATED_WITH
Object
COVID-19
7. Vascular occlusion COEXISTS_WITH COVID-19
Subject
Vascular occlusion
Predicate
COEXISTS_WITH
Object
COVID-19
8. Postmortem tissue sample LOCATION_OF Transection (procedure)
Subject
Postmortem tissue sample
Predicate
LOCATION_OF
Object
Transection (procedure)
9. Blood Vessel LOCATION_OF COVID-19
Subject
Blood Vessel
Predicate
LOCATION_OF
Object
COVID-19
10. Blood Vessel LOCATION_OF Complete obstruction
Subject
Blood Vessel
Predicate
LOCATION_OF
Object
Complete obstruction
11. Blood Vessel LOCATION_OF Congestion
Subject
Blood Vessel
Predicate
LOCATION_OF
Object
Congestion
12. Single organ dysfunction ASSOCIATED_WITH COVID-19
Subject
Single organ dysfunction
Predicate
ASSOCIATED_WITH
Object
COVID-19
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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Thrombosis / Coronavirus Infections / Microvessels / Extracellular Traps / Neutrophils Type of study: Etiology study Limits: Humans Language: English Journal: EBioMedicine Year: 2020 Document Type: Article

Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Thrombosis / Coronavirus Infections / Microvessels / Extracellular Traps / Neutrophils Type of study: Etiology study Limits: Humans Language: English Journal: EBioMedicine Year: 2020 Document Type: Article