{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T16:55:28Z","timestamp":1782924928212,"version":"3.54.5"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chulalongkorn University Ratchadapiseksompotch Fund","award":["RA 63\/082"],"award-info":[{"award-number":["RA 63\/082"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neutrophil Extracellular Traps (NETs) are a contributing factor of vascular thrombosis and alveolar damage in COVID-19 patients. As enoxaparin is currently used to inhibit vascular thrombosis, this study aimed to investigate whether enoxaparin also reduced inflammation and NETs in COVID-19 patients. Patients with COVID-19 infection were classified into three groups: mild, moderate, and severe (n = 10 for all groups). Plasma was collected from patients and healthy donors (n = 10). Neutrophils isolated from healthy controls were incubated with COVID-19 or healthy plasma, and with or without enoxaparin pretreatment in vitro. Neutrophils and plasma isolated from patients treated with enoxaparin were also investigated. The levels of inflammatory cytokines and NET products such as dsDNA, NE, MPO\u2013DNA and Histone\u2013DNA complexes in plasma and supernatants were measured using immunofluorescence staining and ELISA kits. The expression of inflammatory signaling genes by neutrophils (RELA, SYK, ERK and PKC) was measured using real-time qPCR. The levels of NET products were elevated in the plasma of COVID-19 patients, particularly in the severe group (p &lt; 0.01). Moreover, plasma from the severe group enhanced NET formation (p &lt; 0.01) from neutrophils in vitro. Enoxaparin pretreatment in vitro decreased plasma-induced NETs in a dose-dependent manner and down-regulated the expression of inflammatory genes (p &lt; 0.05). Patients treated with prophylactic enoxaparin showed lower inflammatory cytokine levels and expression of inflammatory genes (p &lt; 0.05). Increased NETs were associated with the severity of COVID-19 infection, particularly in patients with severe pneumonia, and could be used as biomarkers to assess disease severity. Enoxaparin pretreatment inhibited NETs and reduced the expression of inflammatory cytokines, and these effects mostly persisted in patients treated with prophylactic enoxaparin.<\/jats:p>","DOI":"10.3390\/ijms23094805","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T13:40:57Z","timestamp":1651066857000},"page":"4805","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Anti-Inflammatory Effects and Decreased Formation of Neutrophil Extracellular Traps by Enoxaparin in COVID-19 Patients"],"prefix":"10.3390","volume":"23","author":[{"given":"Supichcha","family":"Saithong","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Translational Research in Inflammation and Immunology Research Unit (TRIRU), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Immunology and Immune-Mediated Diseases, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0074-0389","authenticated-orcid":false,"given":"Wilasinee","family":"Saisorn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Translational Research in Inflammation and Immunology Research Unit (TRIRU), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Immunology and Immune-Mediated Diseases, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Punyot","family":"Tovichayathamrong","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9329-8189","authenticated-orcid":false,"given":"Grace","family":"Filbertine","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Translational Research in Inflammation and Immunology Research Unit (TRIRU), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 7ZX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9507-6339","authenticated-orcid":false,"given":"Pattama","family":"Torvorapanit","sequence":"additional","affiliation":[{"name":"Thai Red Cross Emerging Infectious Diseases Clinical Center, King Chulalongkorn Memorial Hospital, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0442-3134","authenticated-orcid":false,"given":"Helen L.","family":"Wright","sequence":"additional","affiliation":[{"name":"Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 7ZX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven W.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Institute of Infection, Veterinary and Ecological Sciences, University of Liverpool, Liverpool L69 7ZX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asada","family":"Leelahavanichkul","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Translational Research in Inflammation and Immunology Research Unit (TRIRU), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Immunology and Immune-Mediated Diseases, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nattiya","family":"Hirankarn","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Immunology and Immune-Mediated Diseases, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1824-7012","authenticated-orcid":false,"given":"Direkrit","family":"Chiewchengchol","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Translational Research in Inflammation and Immunology Research Unit (TRIRU), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"},{"name":"Center of Excellence in Immunology and Immune-Mediated Diseases, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1007\/s00408-020-00408-4","article-title":"ACE2: The Major Cell Entry Receptor for SARS-CoV-2","volume":"198","author":"Scialo","year":"2020","journal-title":"Lung"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1007\/s10096-020-04138-6","article-title":"COVID-19: Angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection","volume":"40","author":"Beyerstedt","year":"2021","journal-title":"Eur. 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