Neutrophil extracellular traps and thrombosis in COVID-19

Pedersen SF, Ho YC (2020) SARS-CoV-2: a storm is raging. J Clin Invest. https://doi.org/10.1172/JCI137647 Zhang B, Zhou X, Zhu C, Feng F, Qiu Y, Feng J, Jia Q, Song Q, Zhu B, Wang J (2020) Immune phenotyping based on neutrophil-to-lymphocyte ratio and IgG predicts disease severity and outcome for patients with COVID-19.2020.2003.2012.20035048. doi:https://doi.org/10.1101/2020.03.12.20035048 %J medRxiv Song C-Y, Xu J, He J-Q, Lu Y-Q (2020) COVID-19 early warning score: a multi-parameter screening tool to identify highly suspected patients.2020.2003.2005.20031906. doi:https://doi.org/10.1101/2020.03.05.20031906 %J medRxiv Iba T, Levy JH, Raj A, Warkentin TE (2019) Advance in the management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Clin Med. https://doi.org/10.3390/jcm8050728 Ward PA, Fattahi F (2019) New strategies for treatment of infectious sepsis. J Leukoc Biol 106(1):187–192. https://doi.org/10.1002/JLB.4MIR1118-425R Ali RA, Gandhi AA, Meng H, Yalavarthi S, Vreede AP, Estes SK, Palmer OR, Bockenstedt PL, Pinsky DJ, Greve JM, Diaz JA, Kanthi Y, Knight JS (2019) Adenosine receptor agonism protects against NETosis and thrombosis in antiphospholipid syndrome. Nat Commun 10(1):1916. https://doi.org/10.1038/s41467-019-09801-x Meng H, Yalavarthi S, Kanthi Y, Mazza LF, Elfline MA, Luke CE, Pinsky DJ, Henke PK, Knight JS (2017) In vivo role of neutrophil extracellular traps in antiphospholipid antibody-mediated venous thrombosis. Arthritis Rheumatol 69(3):655–667. https://doi.org/10.1002/art.39938 Yadav V, Chi L, Zhao R, Tourdot BE, Yalavarthi S, Jacobs BN, Banka A, Liao H, Koonse S, Anyanwu AC, Visovatti SH, Holinstat MA, Kahlenberg JM, Knight JS, Pinsky DJ, Kanthi Y (2019) Ectonucleotidase tri(di)phosphohydrolase-1 (ENTPD-1) disrupts inflammasome/interleukin 1beta-driven venous thrombosis. J Clin Invest 129(7):2872–2877. https://doi.org/10.1172/JCI124804 Potey PM, Rossi AG, Lucas CD, Dorward DA (2019) Neutrophils in the initiation and resolution of acute pulmonary inflammation: understanding biological function and therapeutic potential. J Pathol 247(5):672–685. https://doi.org/10.1002/path.5221 Frantzeskaki F, Armaganidis A, Orfanos SE (2017) Immunothrombosis in acute respiratory distress syndrome: cross talks between inflammation and coagulation. Respiration 93(3):212–225. https://doi.org/10.1159/000453002 Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A (2004) Neutrophil extracellular traps kill bacteria. Science 303(5663):1532–1535. https://doi.org/10.1126/science.1092385 Warnatsch A, Ioannou M, Wang Q, Papayannopoulos V (2015) Inflammation: Neutrophil extracellular traps license macrophages for cytokine production in atherosclerosis. Science 349(6245):316–320. https://doi.org/10.1126/science.aaa8064 Doring Y, Soehnlein O, Weber C (2017) Neutrophil extracellular traps in atherosclerosis and atherothrombosis. Circ Res 120(4):736–743. https://doi.org/10.1161/CIRCRESAHA.116.309692 Brill A, Fuchs TA, Savchenko AS, Thomas GM, Martinod K, De Meyer SF, Bhandari AA, Wagner DD (2012) Neutrophil extracellular traps promote deep vein thrombosis in mice. J Thromb Haemost 10(1):136–144. https://doi.org/10.1111/j.1538-7836.2011.04544.x Tanaka K, Koike Y, Shimura T, Okigami M, Ide S, Toiyama Y, Okugawa Y, Inoue Y, Araki T, Uchida K, Mohri Y, Mizoguchi A, Kusunoki M (2014) In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model. PLoS ONE 9(11):e111888. https://doi.org/10.1371/journal.pone.0111888 Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B (2020) Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 395(10229):1054–1062. https://doi.org/10.1016/S0140-6736(20)30566-3 Bunce PE, High SM, Nadjafi M, Stanley K, Liles WC, Christian MD (2011) Pandemic H1N1 influenza infection and vascular thrombosis. Clin Infect Dis 52(2):e14-17. https://doi.org/10.1093/cid/ciq125 Colling ME, Kanthi Y (2020) COVID–19-associated coagulopathy: An exploration of mechanisms. Vascular Medicine 25(5):471–478 Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, Blair CN, Weber A, Barnes BJ, Egeblad M, Woods RJ, Kanthi Y, Knight JS (2020) Neutrophil extracellular traps in COVID-19. JCI Insight. https://doi.org/10.1172/jci.insight.138999 Middleton EA, He XY, Denorme F, Campbell RA, Ng D, Salvatore SP, Mostyka M, Baxter-Stoltzfus A, Borczuk AC, Loda M, Cody MJ, Manne BK, Portier I, Harris ES, Petrey AC, Beswick EJ, Caulin AF, Iovino A, Abegglen LM, Weyrich AS, Rondina MT, Egeblad M, Schiffman JD, Yost CC (2020) Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood 136(10):1169–1179. https://doi.org/10.1182/blood.2020007008 Leppkes M, Knopf J, Naschberger E, Lindemann A, Singh J, Herrmann I, Sturzl M, Staats L, Mahajan A, Schauer C, Kremer AN, Volkl S, Amann K, Evert K, Falkeis C, Wehrfritz A, Rieker RJ, Hartmann A, Kremer AE, Neurath MF, Munoz LE, Schett G, Herrmann M (2020) Vascular occlusion by neutrophil extracellular traps in COVID-19. EBioMedicine 58:102925. https://doi.org/10.1016/j.ebiom.2020.102925 Barnes BJ, Adrover JM, Baxter-Stoltzfus A, Borczuk A, Cools-Lartigue J, Crawford JM, Dassler-Plenker J, Guerci P, Huynh C, Knight JS, Loda M, Looney MR, McAllister F, Rayes R, Renaud S, Rousseau S, Salvatore S, Schwartz RE, Spicer JD, Yost CC, Weber A, Zuo Y, Egeblad M (2020) Targeting potential drivers of COVID-19: neutrophil extracellular traps. J Exp Med. https://doi.org/10.1084/jem.20200652 Skendros P, Mitsios A, Chrysanthopoulou A, Mastellos DC, Metallidis S, Rafailidis P, Ntinopoulou M, Sertaridou E, Tsironidou V, Tsigalou C, Tektonidou MG, Konstantinidis T, Papagoras C, Mitroulis I, Germanidis G, Lambris JD, Ritis K (2020) Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 immunothrombosis. J Clin Invest. https://doi.org/10.1172/JCI141374 Radermecker C, Detrembleur N, Guiot J, Cavalier E, Henket M, d’Emal C, Vanwinge C, Cataldo D, Oury C, Delvenne P, Marichal T (2020) Neutrophil extracellular traps infiltrate the lung airway, interstitial, and vascular compartments in severe COVID-19. J Exp Med. https://doi.org/10.1084/jem.20201012 Nicolai L, Leunig A, Brambs S, Kaiser R, Weinberger T, Weigand M, Muenchhoff M, Hellmuth JC, Ledderose S, Schulz H, Scherer C, Rudelius M, Zoller M, Hochter D, Keppler O, Teupser D, Zwissler B, von Bergwelt-Baildon M, Kaab S, Massberg S, Pekayvaz K, Stark K (2020) Immunothrombotic dysregulation in COVID-19 pneumonia is associated with respiratory failure and coagulopathy. Circulation 142(12):1176–1189. https://doi.org/10.1161/CIRCULATIONAHA.120.048488 Shi H, Zuo Y, Yalavarthi S, Gockman K, Zuo M, Madison JA, Blair C, Woodward W, Lezak SP, Lugogo NL, Woods RJ, Lood C, Knight JS, Kanthi Y (2020) Neutrophil calprotectin identifies severe pulmonary disease in COVID-19. J Leukoc Biol. https://doi.org/10.1002/JLB.3COVCRA0720-359R Kessenbrock K, Krumbholz M, Schonermarck U, Back W, Gross WL, Werb Z, Grone HJ, Brinkmann V, Jenne DE (2009) Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med 15(6):623–625. https://doi.org/10.1038/nm.1959nm.1959[pii] Zuo Y, Estes SK, Ali RA, Gandhi AA, Yalavarthi S, Shi H, Sule G, Gockman K, Madison JA, Zuo M, Yadav V, Wang J, Woodard W, Lezak SP, Lugogo NL, Smith SA, Morrissey JH, Kanthi Y, Knight JS (2020) Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Sci Transl Med:eabd3876. https://doi.org/10.1126/scitranslmed.abd3876 Tang N, Li D, Wang X, Sun Z (2020) Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost 18(4):844–847. https://doi.org/10.1111/jth.14768 Han H, Yang L, Liu R, Liu F, Wu KL, Li J, Liu XH, Zhu CL (2020) Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. https://doi.org/10.1515/cclm-2020-0188 Pfeiler S, Massberg S, Engelmann B (2014) Biological basis and pathological relevance of microvascular thrombosis. Thromb Res 133(Suppl 1):S35-37. https://doi.org/10.1016/j.thromres.2014.03.016 Ma AC, Kubes P (2008) Platelets, neutrophils, and neutrophil extracellular traps (NETs) in sepsis. J Thromb Haemost 6(3):415–420. https://doi.org/10.1111/j.1538-7836.2007.02865.x Gould TJ, Vu TT, Swystun LL, Dwivedi DJ, Mai SH, Weitz JI, Liaw PC (2014) Neutrophil extracellular traps promote thrombin generation through platelet-dependent and platelet-independent mechanisms. Arterioscler Thromb Vasc Biol 34(9):1977–1984. https://doi.org/10.1161/ATVBAHA.114.304114 Kambas K, Chrysanthopoulou A, Vassilopoulos D, Apostolidou E, Skendros P, Girod A, Arelaki S, Froudarakis M, Nakopoulou L, Giatromanolaki A, Sidiropoulos P, Koffa M, Boumpas DT, Ritis K, Mitroulis I (2014) Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease. Ann Rheum Dis 73(10):1854–1863. https://doi.org/10.1136/annrheumdis-2013-203430 Wang Y, Luo L, Braun OO, Westman J, Madhi R, Herwald H, Morgelin M, Thorlacius H (2018) Neutrophil extracellular trap-microparticle complexes enhance thrombin generation via the intrinsic pathway of coagulation in mice. Sci Rep 8(1):4020. https://doi.org/10.1038/s41598-018-22156-5 Massberg S, Grahl L, von Bruehl ML, Manukyan D, Pfeiler S, Goosmann C, Brinkmann V, Lorenz M, Bidzhekov K, Khandagale AB, Konrad I, Kennerknecht E, Reges K, Holdenrieder S, Braun S, Reinhardt C, Spannagl M, Preissner KT, Engelmann B (2010) Reciprocal coupling of coagulation and innate immunity via neutrophil serine proteases. Nat Med 16(8):887–896. https://doi.org/10.1038/nm.2184 Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, Mehra MR, Schuepbach RA, Ruschitzka F, Moch H (2020) Endothelial cell infection and endotheliitis in COVID-19. Lancet 395(10234):1417–1418. https://doi.org/10.1016/S0140-6736(20)30937-5 Nakazawa D, Ishizu A (2020) Immunothrombosis in severe COVID-19. EBioMedicine 59:102942. https://doi.org/10.1016/j.ebiom.2020.102942 Thalin C, Hisada Y, Lundstrom S, Mackman N, Wallen H (2019) Neutrophil extracellular traps: villains and targets in arterial, venous, and cancer-associated thrombosis. Arterioscler Thromb Vasc Biol 39(9):1724–1738. https://doi.org/10.1161/ATVBAHA.119.312463 Barnado A, Crofford LJ, Oates JC (2016) At the Bedside: Neutrophil extracellular traps (NETs) as targets for biomarkers and therapies in autoimmune diseases. J Leukoc Biol 99(2):265–278. https://doi.org/10.1189/jlb.5BT0615-234R Kanthi Y, Knight JS, Zuo Y, Pinsky DJ (2020) New (re)purpose for an old drug: purinergic modulation may extinguish the COVID-19 thromboinflammatory firestorm. JCI Insight 5(14)