PMID- 32329756 OWN - NLM STAT- MEDLINE DCOM- 20200611 LR - 20240329 IS - 2379-3708 (Electronic) IS - 2379-3708 (Linking) VI - 5 IP - 11 DP - 2020 Jun 4 TI - Neutrophil extracellular traps in COVID-19. LID - 138999 [pii] LID - 10.1172/jci.insight.138999 [doi] LID - e138999 AB - In severe cases of coronavirus disease 2019 (COVID-19), viral pneumonia progresses to respiratory failure. Neutrophil extracellular traps (NETs) are extracellular webs of chromatin, microbicidal proteins, and oxidant enzymes that are released by neutrophils to contain infections. However, when not properly regulated, NETs have the potential to propagate inflammation and microvascular thrombosis - including in the lungs of patients with acute respiratory distress syndrome. We now report that sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase-DNA (MPO-DNA), and citrullinated histone H3 (Cit-H3); the latter 2 are specific markers of NETs. Highlighting the potential clinical relevance of these findings, cell-free DNA strongly correlated with acute-phase reactants, including C-reactive protein, D-dimer, and lactate dehydrogenase, as well as absolute neutrophil count. MPO-DNA associated with both cell-free DNA and absolute neutrophil count, while Cit-H3 correlated with platelet levels. Importantly, both cell-free DNA and MPO-DNA were higher in hospitalized patients receiving mechanical ventilation as compared with hospitalized patients breathing room air. Finally, sera from individuals with COVID-19 triggered NET release from control neutrophils in vitro. Future studies should investigate the predictive power of circulating NETs in longitudinal cohorts and determine the extent to which NETs may be novel therapeutic targets in severe COVID-19. FAU - Zuo, Yu AU - Zuo Y AD - Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Yalavarthi, Srilakshmi AU - Yalavarthi S AD - Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Shi, Hui AU - Shi H AD - Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. AD - Division of Rheumatology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Gockman, Kelsey AU - Gockman K AD - Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Zuo, Melanie AU - Zuo M AD - Division of Geriatric and Palliative Medicine and. FAU - Madison, Jacqueline A AU - Madison JA AD - Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Blair, Christopher AU - Blair C AD - Division of Infectious Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Weber, Andrew AU - Weber A AD - Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Northwell Health, New York, New York, USA. FAU - Barnes, Betsy J AU - Barnes BJ AD - Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institutes for Medical Research, Manhasset, New York, USA. AD - Departments of Molecular Medicine and Pediatrics, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA. FAU - Egeblad, Mikala AU - Egeblad M AD - Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, USA. FAU - Woods, Robert J AU - Woods RJ AD - Division of Infectious Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. FAU - Kanthi, Yogendra AU - Kanthi Y AD - Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. AD - Division of Cardiology, VA Ann Arbor Healthcare System, Ann Arbor, Michigan, USA. FAU - Knight, Jason S AU - Knight JS AD - Division of Rheumatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA. LA - eng GR - R01 HL115138/HL/NHLBI NIH HHS/United States GR - K08 HL131993/HL/NHLBI NIH HHS/United States GR - WT_/Wellcome Trust/United Kingdom GR - R01 HL150392/HL/NHLBI NIH HHS/United States GR - R01 HL134846/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200604 PL - United States TA - JCI Insight JT - JCI insight JID - 101676073 RN - 0 (Cell-Free Nucleic Acids) RN - 0 (Fibrin Fibrinogen Degradation Products) RN - 0 (Histones) RN - 0 (fibrin fragment D) RN - 9007-41-4 (C-Reactive Protein) RN - EC 1.1.1.27 (L-Lactate Dehydrogenase) RN - EC 1.11.1.7 (Peroxidase) SB - IM UOF - medRxiv. 2020 May 05;:. PMID: 32511553 UOF - medRxiv. 2020 Apr 14;:. PMID: 32511633 MH - Adult MH - Aged MH - Aged, 80 and over MH - C-Reactive Protein/metabolism MH - COVID-19 MH - Case-Control Studies MH - Cell-Free Nucleic Acids/*metabolism MH - Citrullination MH - Coronavirus Infections/blood/*metabolism/therapy MH - Extracellular Traps/*metabolism MH - Female MH - Fibrin Fibrinogen Degradation Products/metabolism MH - Histones/*metabolism MH - Humans MH - In Vitro Techniques MH - L-Lactate Dehydrogenase/metabolism MH - Lymphocyte Count MH - Male MH - Middle Aged MH - Neutrophils/*metabolism MH - Pandemics MH - Peroxidase/*metabolism MH - Platelet Count MH - Pneumonia, Viral/blood/*metabolism/therapy MH - Respiration, Artificial MH - Severity of Illness Index PMC - PMC7308057 OTO - NOTNLM OT - Infectious disease OT - Inflammation OT - Neutrophils COIS- Conflict of interest: ME reports receipt of lonodelestat from Santhera for preclinical studies. EDAT- 2020/04/25 06:00 MHDA- 2020/06/12 06:00 PMCR- 2020/06/04 CRDT- 2020/04/25 06:00 PHST- 2020/04/09 00:00 [received] PHST- 2020/04/23 00:00 [accepted] PHST- 2020/04/25 06:00 [pubmed] PHST- 2020/06/12 06:00 [medline] PHST- 2020/04/25 06:00 [entrez] PHST- 2020/06/04 00:00 [pmc-release] AID - 138999 [pii] AID - 10.1172/jci.insight.138999 [doi] PST - epublish SO - JCI Insight. 2020 Jun 4;5(11):e138999. doi: 10.1172/jci.insight.138999.