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The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome

Open access
Middleton, Elizabeth A., He, Xue-Yan, Denorme, Frederik, Campbell, Robert A., Ng, David, Salvatore, Steven P., Mostyka, Maria, Baxter-Stoltzfus, Amelia, Borczuk, Alain C., Loda, Massimo, Cody, Mark J., Manne, Bhanu Kanth, Portier, Irina, Harris, Estelle S., Petrey, Aaron C., Beswick, Ellen J., Caulin, Aleah F., Iovino, Anthony, Abegglen, Lisa M., Weyrich, Andrew S., Rondina, Matthew T., Egeblad, Mikala, Schiffman, Joshua D., Yost, Christian Con·2020·Blood

Abstract

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support. Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis. We studied the connection between NETs and COVID-19 severity and progression. We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17). We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines. Three COVID-19 lung autopsies were examined for NETs and platelet involvement. We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma. We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma. Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome. Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340). Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration. Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF. Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.

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Metadata

Authors
Middleton, E. A., He, X.-Y., Denorme, F., Campbell, R. A., Ng, D., Salvatore, S. P., Mostyka, M., Baxter-Stoltzfus, A., Borczuk, A. C., Loda, M., Cody, M. J., Manne, B. K., Portier, I., Harris, E. S., Petrey, A. C., Beswick, E. J., Caulin, A. F., Iovino, A., Abegglen, L. M., Weyrich, A. S., Rondina, M. T., Egeblad, M., Schiffman, J. D., & Yost, C. C.
Venue
Blood
Published
2020-09-03
Volume
136
Issue
10
Pages
1169-1179
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
OpenAlex
W3037020655
Cited by
1,460
References
10
FWCI
77.10
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. https://app.cochat.ai/papers/10.1182/blood.2020007008
The paper
Middleton, E. A., He, X.-Y., Denorme, F., Campbell, R. A., Ng, D., Salvatore, S. P., Mostyka, M., Baxter-Stoltzfus, A., Borczuk, A. C., Loda, M., Cody, M. J., Manne, B. K., Portier, I., Harris, E. S., Petrey, A. C., Beswick, E. J., Caulin, A. F., Iovino, A., Abegglen, L. M., . . . Yost, C. C. (2020). Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood. https://doi.org/10.1182/blood.2020007008

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

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