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Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome.
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.
Afiliação
  • Middleton EA; Molecular Medicine Program and.
  • He XY; Department of Internal Medicine, University of Utah, Salt Lake City, UT.
  • Denorme F; Cold Spring Harbor Laboratory, Cancer Center, Cold Spring Harbor, NY.
  • Campbell RA; Molecular Medicine Program and.
  • Ng D; Molecular Medicine Program and.
  • Salvatore SP; Department of Internal Medicine, University of Utah, Salt Lake City, UT.
  • Mostyka M; Cold Spring Harbor Laboratory, Cancer Center, Cold Spring Harbor, NY.
  • Baxter-Stoltzfus A; Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
  • Borczuk AC; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.
  • Loda M; Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
  • Cody MJ; Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
  • Manne BK; Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
  • Portier I; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.
  • Harris ES; Department of Pathology and Laboratory Medicine, New York Presbyterian Hospital, New York, NY.
  • Petrey AC; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY.
  • Beswick EJ; Molecular Medicine Program and.
  • Caulin AF; Department of Pediatrics and.
  • Iovino A; Molecular Medicine Program and.
  • Abegglen LM; Molecular Medicine Program and.
  • Weyrich AS; Department of Internal Medicine, University of Utah, Salt Lake City, UT.
  • Rondina MT; Molecular Medicine Program and.
  • Egeblad M; Department of Pathology, University of Utah, Salt Lake City, UT.
  • Schiffman JD; Department of Internal Medicine, University of Utah, Salt Lake City, UT.
  • Yost CC; PEEL Therapeutics, Inc, Salt Lake City, UT; and.
Blood ; 136(10): 1169-1179, 2020 09 03.
Article em En | MEDLINE | ID: mdl-32597954
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.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pneumonia Viral / Trombose / Infecções por Coronavirus / Armadilhas Extracelulares / Neutrófilos Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Pneumonia Viral / Trombose / Infecções por Coronavirus / Armadilhas Extracelulares / Neutrófilos Tipo de estudo: Observational_studies / Risk_factors_studies Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2020 Tipo de documento: Article