{"doi":"10.1101/2020.04.30.20086736","title":"Neutrophil extracellular traps and thrombosis in COVID-19","abstract":"BACKGROUND: Early studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events. While elevated levels of blood neutrophils and neutrophil extracellular traps (NETs) have been described in patients with COVID-19, their potential role in COVID-19-associated thrombosis remains unknown. OBJECTIVES: To elucidate the potential role of hyperactive neutrophils and NET release in COVID-19-associated thrombosis. PATIENTS/METHODS: This is a retrospective, case-control study of patients hospitalized with COVID-19 who developed thrombosis (n=11), as compared with gender- and age-matched COVID-19 patients without clinical thrombosis (n=33). In addition to capturing clinical data, we measured remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera. RESULTS: The majority of patients (9/11) were receiving at least prophylactic doses of heparinoids at the time thrombosis was diagnosed. As compared with controls, patients with COVID-19-associated thrombosis had significantly higher blood levels of markers of NETs (cell-free DNA, myeloperoxidase-DNA complexes, citrullinated histone H3) and neutrophil activation (calprotectin). The thrombosis group also had higher levels of D-dimer, CRP, ferritin, and platelets, but not troponin or neutrophils. Finally, there were strong associations between markers of hyperactive neutrophils (calprotectin and cell-free DNA) and D-dimer. CONCLUSION: Elevated levels of neutrophil activation and NET formation in patients hospitalized with COVID-19 are associated with higher risk of morbid thrombotic complications. These observations underscore the need for urgent investigation into the potential relationship between NETs and unrelenting thrombosis in COVID-19.","journal":"medRxiv","year":2020,"id":118387,"datarank":0.6830815337400812,"base_score":4.553876891600541,"endowment":4.553876891600541,"self_citation_contribution":0.6830815337400812,"citation_network_contribution":0.0,"self_endowment_contribution":0.6830815337400812,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":94,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9573,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":105694,"name":"Melanie Zuo","orcid":null,"position":1,"is_corresponding":false},{"id":105691,"name":"Srilakshmi Yalavarthi","orcid":"0009-0005-9128-572X","position":2,"is_corresponding":false},{"id":105693,"name":"Kelsey Gockman","orcid":null,"position":3,"is_corresponding":false},{"id":105695,"name":"Jacqueline A. Madison","orcid":"0000-0003-1745-8133","position":4,"is_corresponding":false},{"id":105692,"name":"Hui Shi","orcid":"0000-0003-0564-3059","position":5,"is_corresponding":false},{"id":105701,"name":"Jason S. Knight","orcid":"0000-0003-0995-9771","position":6,"is_corresponding":false},{"id":105700,"name":"Yogendra Kanthi","orcid":"0000-0002-5660-5194","position":7,"is_corresponding":false},{"id":259811,"name":"Yu Zuo","orcid":"0000-0001-6721-7755","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:13:58.531532Z","pmid":"32511553","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}