{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:43:00Z","timestamp":1791996180616,"version":"4.4.0"},"reference-count":100,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,11,1]],"date-time":"2022-11-01T00:00:00Z","timestamp":1667260800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Eur J Immunol"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Acute respiratory distress syndrome (ARDS) is an acute inflammatory condition with a dramatic increase in incidence since the beginning of the coronavirus disease 19 (COVID\u201019) pandemic. Neutrophils play a vital role in the immunopathology of severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) infection by triggering the formation of neutrophil extracellular traps (NETs), producing cytokines including interleukin\u20108 (CXCL8), and mediating the recruitment of other immune cells to regulate processes such as acute and chronic inflammation, which can lead to ARDS. CXCL8 is involved in the recruitment, activation, and degranulation of neutrophils, and therefore contributes to inflammation amplification and severity of disease. Furthermore, activation of neutrophils also supports a prothrombotic phenotype, which may explain the development of immunothrombosis observed in COVID\u201019 ARDS. This review aims to describe hyperinflammatory ARDS due to SARS\u2010CoV\u20102 infection. In addition, we address the critical role of polymorphonuclear neutrophils, inflammatory cytokines, and the potential targeting of CXCL8 in treating the hyperinflammatory ARDS population.<\/jats:p>","DOI":"10.1002\/eji.202250010","type":"journal-article","created":{"date-parts":[[2022,10,14]],"date-time":"2022-10-14T04:54:16Z","timestamp":1665723256000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":110,"title":["Neutrophil activation and neutrophil extracellular traps (NETs) in COVID\u201019 ARDS and immunothrombosis"],"prefix":"10.1002","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4847-2985","authenticated-orcid":false,"given":"Maria Candida","family":"Cesta","sequence":"first","affiliation":[{"name":"Domp\u00e9 farmaceutici SpA  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3749-1176","authenticated-orcid":false,"given":"Mara","family":"Zippoli","sequence":"additional","affiliation":[{"name":"Domp\u00e9 farmaceutici SpA  Napoli Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4510-9582","authenticated-orcid":false,"given":"Carolina","family":"Marsiglia","sequence":"additional","affiliation":[{"name":"Domp\u00e9 farmaceutici SpA  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth M.","family":"Gavioli","sequence":"additional","affiliation":[{"name":"Domp\u00e9 U.S. Inc.  Boston USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giada","family":"Cremonesi","sequence":"additional","affiliation":[{"name":"Domp\u00e9 Farmaceutici S.p.A.  Milano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3091-632X","authenticated-orcid":false,"given":"Akram","family":"Khan","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, and Critical Care Medicine Oregon Health and Science University  Portland Oregon USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Mantelli","sequence":"additional","affiliation":[{"name":"Domp\u00e9 farmaceutici SpA  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello","family":"Allegretti","sequence":"additional","affiliation":[{"name":"Domp\u00e9 farmaceutici SpA  L'Aquila Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Balk","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine Rush Medical College and Rush University Medical Center  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201609-1773CP"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccc.2021.05.001"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.4037\/ajcc2022549"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00439-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.124.2.653"},{"issue":"23","key":"e_1_2_7_7_1","first-page":"2526","article-title":"Acute respiratory distress syndrome: the Berlin Definition","volume":"307","author":"Force A.D.T.","year":"2012","journal-title":"JAMA"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.21037\/jtd.2018.12.24"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1092385"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201719"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.5114\/ceji.2019.84017"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/849136"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201006052"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(14)70097-9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0317-2020"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-05991-x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-13179-0"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12879-021-06015-9"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/thoraxjnl-2016-209170"},{"key":"e_1_2_7_20_1","article-title":"NETosis and Neutrophil Extracellular Traps in COVID\u201019: Immunothrombosis and Beyond","volume":"13","author":"Zhu Y.","year":"2022","journal-title":"Frontiers in Immunology"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccm.2016.11.013"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcrc.2018.07.002"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.202005-1583OC"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071817"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-32576-y"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004651"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.12688\/wellcomeopenres.16584.2"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.51811"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12952"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00454-7"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6615787"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/openhrt-2020-001337"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2021-0137"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00776"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2018.01.004"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007008"},{"issue":"11","key":"e_1_2_7_37_1","article-title":"Neutrophil extracellular traps in COVID\u201019","volume":"5","author":"Zuo Y.","year":"2020","journal-title":"JCI Insight"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.102925"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.04.012"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1100450"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0902199"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.148435"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009721"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20201129"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.118.10266"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI141374"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148142"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14869"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006000"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.152291"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2020.04.002"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.01648"},{"key":"e_1_2_7_53_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01169"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiab053"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(20)30216-7"},{"key":"e_1_2_7_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.04.013"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14888"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-020-06062-x"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31305-2"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-020-00954-7"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01608-2020"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0968-3"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.trsl.2020.04.007"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105368"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2020.06.027"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.048488"},{"key":"e_1_2_7_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-018-0024-0"},{"key":"e_1_2_7_68_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2019.00085"},{"key":"e_1_2_7_69_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1005743107"},{"key":"e_1_2_7_70_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0048111"},{"key":"e_1_2_7_71_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0244628"},{"key":"e_1_2_7_72_1","doi-asserted-by":"publisher","DOI":"10.7150\/thno.49713"},{"key":"e_1_2_7_73_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-020-02224-2"},{"key":"e_1_2_7_74_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3COVR0520-272R"},{"key":"e_1_2_7_75_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.150862"},{"key":"e_1_2_7_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-021-00536-9"},{"key":"e_1_2_7_77_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa756"},{"key":"e_1_2_7_78_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.98178"},{"key":"e_1_2_7_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02536"},{"key":"e_1_2_7_80_1","first-page":"678","article-title":"Unraveling the Dark Side of Old Diseases through Neutrophils","volume":"7","author":"Mitsios A.","year":"2016","journal-title":"Frontiers in immunology"},{"key":"e_1_2_7_81_1","doi-asserted-by":"publisher","DOI":"10.1159\/000492950"},{"key":"e_1_2_7_82_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0000000000002619"},{"key":"e_1_2_7_83_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.11330"},{"key":"e_1_2_7_84_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00870"},{"key":"e_1_2_7_85_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2021436"},{"key":"e_1_2_7_86_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-019-2336-6"},{"key":"e_1_2_7_87_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000023656"},{"key":"e_1_2_7_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2020.155389"},{"key":"e_1_2_7_89_1","doi-asserted-by":"publisher","DOI":"10.21037\/apm-20-2134"},{"key":"e_1_2_7_90_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-020-00821-7"},{"key":"e_1_2_7_91_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-022-00644-6"},{"key":"e_1_2_7_92_1","article-title":"Lenzilumab in hospitalised patients with COVID\u201019 pneumonia (LIVE\u2010AIR): a phase 3, randomised, placebo\u2010controlled trial","author":"Temesgen Z.","year":"2021","journal-title":"Lancet Respir Med"},{"key":"e_1_2_7_93_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01499-z"},{"key":"e_1_2_7_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(21)00377-5"},{"key":"e_1_2_7_95_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines9121867"},{"key":"e_1_2_7_96_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2020.120389"},{"key":"e_1_2_7_97_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcpro.2021.100113"},{"key":"e_1_2_7_98_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.714833"},{"key":"e_1_2_7_99_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2004.05.003"},{"key":"e_1_2_7_100_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pupt.2011.03.001"},{"key":"e_1_2_7_101_1","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e3181aa95c4"}],"container-title":["European Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202250010","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/eji.202250010","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/eji.202250010","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T05:02:46Z","timestamp":1692507766000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/eji.202250010"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11]]},"references-count":100,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2023,1]]}},"alternative-id":["10.1002\/eji.202250010"],"URL":"https:\/\/doi.org\/10.1002\/eji.202250010","archive":["Portico"],"relation":{},"ISSN":["0014-2980","1521-4141"],"issn-type":[{"value":"0014-2980","type":"print"},{"value":"1521-4141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11]]},"assertion":[{"value":"2022-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-10-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2250010"}}