tetano
Editor, Senior Moderator
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[SUP] 1 [/SUP], Jasmin Knopf[SUP] 2 [/SUP], Elisabeth Naschberger[SUP] 3 [/SUP], Aylin Lindemann[SUP] 4 [/SUP], Jeeshan Singh[SUP] 2 [/SUP], Irmgard Herrmann[SUP] 5 [/SUP], Michael St?rzl[SUP] 3 [/SUP], L?onie Staats[SUP] 4 [/SUP], Aparna Mahajan[SUP] 2 [/SUP], Christine Schauer[SUP] 2 [/SUP], Anita N Kremer[SUP] 6 [/SUP], Simon V?lkl[SUP] 6 [/SUP], Kerstin Amann[SUP] 7 [/SUP], Katja Evert[SUP] 8 [/SUP], Christina Falkeis[SUP] 9 [/SUP], Andreas Wehrfritz[SUP] 10 [/SUP], Ralf J Rieker[SUP] 11 [/SUP], Arndt Hartmann[SUP] 11 [/SUP], Andreas E Kremer[SUP] 4 [/SUP], Markus F Neurath[SUP] 4 [/SUP], Luis E Mu?oz[SUP] 2 [/SUP], Georg Schett[SUP] 2 [/SUP], Martin Herrmann[SUP] 2 [/SUP]
Affiliations
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.
. 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[SUP] 1 [/SUP], Jasmin Knopf[SUP] 2 [/SUP], Elisabeth Naschberger[SUP] 3 [/SUP], Aylin Lindemann[SUP] 4 [/SUP], Jeeshan Singh[SUP] 2 [/SUP], Irmgard Herrmann[SUP] 5 [/SUP], Michael St?rzl[SUP] 3 [/SUP], L?onie Staats[SUP] 4 [/SUP], Aparna Mahajan[SUP] 2 [/SUP], Christine Schauer[SUP] 2 [/SUP], Anita N Kremer[SUP] 6 [/SUP], Simon V?lkl[SUP] 6 [/SUP], Kerstin Amann[SUP] 7 [/SUP], Katja Evert[SUP] 8 [/SUP], Christina Falkeis[SUP] 9 [/SUP], Andreas Wehrfritz[SUP] 10 [/SUP], Ralf J Rieker[SUP] 11 [/SUP], Arndt Hartmann[SUP] 11 [/SUP], Andreas E Kremer[SUP] 4 [/SUP], Markus F Neurath[SUP] 4 [/SUP], Luis E Mu?oz[SUP] 2 [/SUP], Georg Schett[SUP] 2 [/SUP], Martin Herrmann[SUP] 2 [/SUP]
Affiliations
- PMID: 32745993
- 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.
Keywords: Aggregated neutrophil extracellular traps; Coagulopathy; Endothelialitis; Immunothrombosis; SARS-CoV-2.