{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:12:50Z","timestamp":1789186370168,"version":"build-2803163510"},"reference-count":171,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T00:00:00Z","timestamp":1685404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,9,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Immunothrombosis\u2014immune-mediated activation of coagulation\u2014is protective against pathogens, but excessive immunothrombosis can result in pathological thrombosis and multiorgan damage, as in severe coronavirus disease 2019 (COVID-19). The NACHT-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome produces major proinflammatory cytokines of the interleukin (IL)-1 family, IL-1\u03b2 and IL-18, and induces pyroptotic cell death. Activation of the NLRP3 inflammasome pathway also promotes immunothrombotic programs including release of neutrophil extracellular traps and tissue factor by leukocytes, and prothrombotic responses by platelets and the vascular endothelium. NLRP3 inflammasome activation occurs in patients with COVID-19 pneumonia. In preclinical models, NLRP3 inflammasome pathway blockade restrains COVID-19-like hyperinflammation and pathology. Anakinra, recombinant human IL-1 receptor antagonist, showed safety and efficacy and is approved for the treatment of hypoxaemic COVID-19 patients with early signs of hyperinflammation. The non-selective NLRP3 inhibitor colchicine reduced hospitalization and death in a subgroup of COVID-19 outpatients but is not approved for the treatment of COVID-19. Additional COVID-19 trials testing NLRP3 inflammasome pathway blockers are inconclusive or ongoing. We herein outline the contribution of immunothrombosis to COVID-19-associated coagulopathy, and review preclinical and clinical evidence suggesting an engagement of the NLRP3 inflammasome pathway in the immunothrombotic pathogenesis of COVID-19. We also summarize current efforts to target the NLRP3 inflammasome pathway in COVID-19, and discuss challenges, unmet gaps, and the therapeutic potential that inflammasome-targeted strategies may provide for inflammation-driven thrombotic disorders including COVID-19.<\/jats:p>","DOI":"10.1093\/cvr\/cvad084","type":"journal-article","created":{"date-parts":[[2023,5,30]],"date-time":"2023-05-30T18:12:56Z","timestamp":1685470376000},"page":"2046-2060","source":"Crossref","is-referenced-by-count":52,"title":["NLRP3 inflammasome and interleukin-1 contributions to COVID-19-associated coagulopathy and immunothrombosis"],"prefix":"10.1093","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6585-4870","authenticated-orcid":false,"given":"Nicola","family":"Potere","sequence":"first","affiliation":[{"name":"Department of Medicine and Ageing Sciences, \u2018G. d\u2019Annunzio\u2019 University , Via Luigi Polacchi 11, Chieti 66100 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Garrad","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Thrombosis and Inflammation, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD , USA"},{"name":"University of Missouri School of Medicine , Columbia, MO , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogendra","family":"Kanthi","sequence":"additional","affiliation":[{"name":"Laboratory of Vascular Thrombosis and Inflammation, National Heart, Lung, and Blood Institute, National Institutes of Health , Bethesda, MD , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Di Nisio","sequence":"additional","affiliation":[{"name":"Department of Medicine and Ageing Sciences, \u2018G. d\u2019Annunzio\u2019 University , Via Luigi Polacchi 11, Chieti 66100 , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Kaplanski","sequence":"additional","affiliation":[{"name":"Aix-Marseille Universit\u00e9, INSERM, INRAE, Marseille, France"},{"name":"Division of Internal Medicine and Clinical Immunology, Assistance Publique - H\u00f4pitaux de Marseille, H\u00f4pital Conception, Aix-Marseille Universit\u00e9, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Bonaventura","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Medicina Generale 1, Medical Center, Ospedale di Circolo e Fondazione Macchi, ASST Sette Laghi , Varese , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Marie","family":"Connors","sequence":"additional","affiliation":[{"name":"Division of Hematology, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1637-574X","authenticated-orcid":false,"given":"Raffaele","family":"De Caterina","sequence":"additional","affiliation":[{"name":"University Cardiology Division, Pisa University Hospital , Pisa , Italy"},{"name":"Chair and Postgraduate School of Cardiology, University of Pisa , Pisa , Italy"},{"name":"Fondazione Villa Serena per la Ricerca, Citt\u00e0 Sant\u2019Angelo , Pescara , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1930-785X","authenticated-orcid":false,"given":"Antonio","family":"Abbate","sequence":"additional","affiliation":[{"name":"Robert M. 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