Patients with COVID-19: in the dark-NETs of neutrophils

SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19....

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Vydáno v:	Cell death and differentiation Ročník 28; číslo 11; s. 3125 - 3139
Hlavní autoři:	Ackermann, Maximilian, Anders, Hans-Joachim, Bilyy, Rostyslav, Bowlin, Gary L, Daniel, Christoph, De Lorenzo, Rebecca, Egeblad, Mikala, Henneck, Timo, Hidalgo, Andrés, Hoffmann, Markus, Hohberger, Bettina, Kanthi, Yogendra, Kaplan, Mariana J, Knight, Jason S, Knopf, Jasmin, Kolaczkowska, Elzbieta, Kubes, Paul, Leppkes, Moritz, Mahajan, Aparna, Manfredi, Angelo A, Maueröder, Christian, Maugeri, Norma, Mitroulis, Ioannis, Muñoz, Luis E, Narasaraju, Teluguakula, Naschberger, Elisabeth, Neeli, Indira, Ng, Lai Guan, Radic, Marko Z, Ritis, Konstantinos, Rovere-Querini, Patrizia, Schapher, Mirco, Schauer, Christine, Simon, Hans-Uwe, Singh, Jeeshan, Skendros, Panagiotis, Stark, Konstantin, Stürzl, Michael, van der Vlag, Johan, Vandenabeele, Peter, Vitkov, Ljubomir, von Köckritz-Blickwede, Maren, Yanginlar, Cansu, Yousefi, Shida, Zarbock, Alexander, Schett, Georg, Herrmann, Martin
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	England Nature Publishing Group 01.11.2021
Témata:	Adaptive immunity Citrullination Complement Activation Coronaviruses COVID-19 COVID-19 - complications COVID-19 - immunology COVID-19 - pathology Extracellular Traps - metabolism Humans Immune response Inflammatory diseases Leukocytes (neutrophilic) Neutrophils Neutrophils - immunology Neutrophils - metabolism Pandemics Patients Platelet Activation SARS-CoV-2 - isolation & purification Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Thrombosis - etiology
ISSN:	1350-9047, 1476-5403, 1476-5403
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Abstract	SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.
AbstractList	SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19. SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb the pandemic, it is paramount to define the mechanisms and develop protective therapies to prevent organ dysfunction in patients with COVID-19. Individuals that develop severe manifestations have signs of dysregulated innate and adaptive immune responses. Emerging evidence implicates neutrophils and the disbalance between neutrophil extracellular trap (NET) formation and degradation plays a central role in the pathophysiology of inflammation, coagulopathy, organ damage, and immunothrombosis that characterize severe cases of COVID-19. Here, we discuss the evidence supporting a role for NETs in COVID-19 manifestations and present putative mechanisms, by which NETs promote tissue injury and immunothrombosis. We present therapeutic strategies, which have been successful in the treatment of immunο-inflammatory disorders and which target dysregulated NET formation or degradation, as potential approaches that may benefit patients with severe COVID-19.
Author	Ackermann, Maximilian Kolaczkowska, Elzbieta van der Vlag, Johan Schett, Georg Radic, Marko Z Bowlin, Gary L Neeli, Indira Knight, Jason S Ng, Lai Guan Mahajan, Aparna Hoffmann, Markus Skendros, Panagiotis Singh, Jeeshan Schapher, Mirco Knopf, Jasmin Vitkov, Ljubomir De Lorenzo, Rebecca Schauer, Christine Yanginlar, Cansu Stark, Konstantin Stürzl, Michael Herrmann, Martin Zarbock, Alexander Kubes, Paul Bilyy, Rostyslav Muñoz, Luis E Henneck, Timo Yousefi, Shida von Köckritz-Blickwede, Maren Hidalgo, Andrés Manfredi, Angelo A Rovere-Querini, Patrizia Simon, Hans-Uwe Maugeri, Norma Daniel, Christoph Mitroulis, Ioannis Maueröder, Christian Kaplan, Mariana J Ritis, Konstantinos Anders, Hans-Joachim Naschberger, Elisabeth Hohberger, Bettina Kanthi, Yogendra Narasaraju, Teluguakula Vandenabeele, Peter Egeblad, Mikala Leppkes, Moritz
Author_xml	– sequence: 1 givenname: Maximilian surname: Ackermann fullname: Ackermann, Maximilian organization: Institute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany – sequence: 2 givenname: Hans-Joachim surname: Anders fullname: Anders, Hans-Joachim organization: Medizinische Klinik und Poliklinik IV, Klinikum der Universität München, Ludwig-Maximilians University Munich, Munich, Germany – sequence: 3 givenname: Rostyslav orcidid: 0000-0002-2344-1349 surname: Bilyy fullname: Bilyy, Rostyslav organization: Danylo Halytsky Lviv National Medical University, Lviv, Ukraine – sequence: 4 givenname: Gary L surname: Bowlin fullname: Bowlin, Gary L organization: Department of Biomedical Engineering, University of Memphis, Memphis, TN, USA – sequence: 5 givenname: Christoph surname: Daniel fullname: Daniel, Christoph organization: Department of Nephropathology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany – sequence: 6 givenname: Rebecca surname: De Lorenzo fullname: De Lorenzo, Rebecca organization: Università Vita-Salute San Raffaele & IRCCS San Raffaele Scientific Institute, Milano, Italy – sequence: 7 givenname: Mikala surname: Egeblad fullname: Egeblad, Mikala organization: Cold Spring Harbor Laboratory Cancer Center, Cold Spring Harbor, NY, USA – sequence: 8 givenname: Timo surname: Henneck fullname: Henneck, Timo organization: Institute for Biochemistry and Research Center for Emerging Infections and Zonoses, University of Veterinary Medicine Hannover, Hannover, Germany – sequence: 9 givenname: Andrés surname: Hidalgo fullname: Hidalgo, Andrés organization: Area of Cell and Developmental Biology, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain – sequence: 10 givenname: Markus orcidid: 0000-0001-9698-9922 surname: Hoffmann fullname: Hoffmann, Markus organization: Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 11 givenname: Bettina surname: Hohberger fullname: Hohberger, Bettina organization: Department of Ophthalmology, University of Erlangen-Nürnberg, Erlangen, Germany – sequence: 12 givenname: Yogendra surname: Kanthi fullname: Kanthi, Yogendra organization: Division of Cardiovascular Medicine, University of Michigan, Ann Arbor, MI, USA – sequence: 13 givenname: Mariana J orcidid: 0000-0003-2968-0815 surname: Kaplan fullname: Kaplan, Mariana J organization: Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA – sequence: 14 givenname: Jason S surname: Knight fullname: Knight, Jason S organization: Division of Rheumatology, University of Michigan, Ann Arbor, MI, USA – sequence: 15 givenname: Jasmin surname: Knopf fullname: Knopf, Jasmin organization: Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 16 givenname: Elzbieta surname: Kolaczkowska fullname: Kolaczkowska, Elzbieta organization: Department of Experimental Hematology, Institute of Zoology and Biomedical Research, Jagiellonian University, Krakow, Poland – sequence: 17 givenname: Paul surname: Kubes fullname: Kubes, Paul organization: Snyder Institute for Chronic Disease, University of Calgary, Alberta, Canada – sequence: 18 givenname: Moritz surname: Leppkes fullname: Leppkes, Moritz organization: Department of Internal Medicine 1, Friedrich Alexander University Erlangen-Nuremberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 19 givenname: Aparna surname: Mahajan fullname: Mahajan, Aparna organization: Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 20 givenname: Angelo A surname: Manfredi fullname: Manfredi, Angelo A organization: Università Vita-Salute San Raffaele & IRCCS San Raffaele Scientific Institute, Milano, Italy – sequence: 21 givenname: Christian surname: Maueröder fullname: Maueröder, Christian organization: Department of Biomedical Molecular Biology (DBMB), Ghent University, Ghent, Belgium – sequence: 22 givenname: Norma orcidid: 0000-0003-3931-0412 surname: Maugeri fullname: Maugeri, Norma organization: Università Vita-Salute San Raffaele & IRCCS San Raffaele Scientific Institute, Milano, Italy – sequence: 23 givenname: Ioannis surname: Mitroulis fullname: Mitroulis, Ioannis organization: First Department of Internal Medicine, Department of Medicine, University Hospital of Alexandroupolis, and Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece – sequence: 24 givenname: Luis E orcidid: 0000-0002-5395-804X surname: Muñoz fullname: Muñoz, Luis E organization: Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 25 givenname: Teluguakula surname: Narasaraju fullname: Narasaraju, Teluguakula organization: School of Health Care Administration, Oklahoma State University Center for Health Sciences, Tulsa, OK, USA – sequence: 26 givenname: Elisabeth surname: Naschberger fullname: Naschberger, Elisabeth organization: Division of Molecular and Experimental Surgery, Translational Research Center, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany – sequence: 27 givenname: Indira surname: Neeli fullname: Neeli, Indira organization: Department of Microbiology, Immunology and Biochemistry, University of Tennessee Health Science Center, Memphis, TN, USA – sequence: 28 givenname: Lai Guan surname: Ng fullname: Ng, Lai Guan organization: Singapore Immunology Network (SIgN), ASTAR, Biopolis, Singapore, Singapore – 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givenname: Christine surname: Schauer fullname: Schauer, Christine organization: Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 34 givenname: Hans-Uwe surname: Simon fullname: Simon, Hans-Uwe organization: Institute of Pharmacology, University of Bern, Inselspital, INO-F, Bern, Switzerland – sequence: 35 givenname: Jeeshan surname: Singh fullname: Singh, Jeeshan organization: Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 36 givenname: Panagiotis surname: Skendros fullname: Skendros, Panagiotis organization: First Department of Internal Medicine, Department of Medicine, University Hospital of Alexandroupolis, and Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece – sequence: 37 givenname: Konstantin surname: Stark fullname: Stark, Konstantin organization: Medizinische Klinik I, Klinikum der Ludwig-Maximilians-Universität, Munich, Germany – sequence: 38 givenname: Michael orcidid: 0000-0002-9276-2824 surname: Stürzl fullname: Stürzl, Michael organization: Division of Molecular and Experimental Surgery, Translational Research Center, Department of Surgery, University Medical Center Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany – sequence: 39 givenname: Johan orcidid: 0000-0001-7843-5918 surname: van der Vlag fullname: van der Vlag, Johan organization: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands – sequence: 40 givenname: Peter orcidid: 0000-0002-6669-8822 surname: Vandenabeele fullname: Vandenabeele, Peter organization: Department of Biomedical Molecular Biology (DBMB) and Methusalem Program, Ghent University, Ghent, Belgium – sequence: 41 givenname: Ljubomir orcidid: 0000-0002-1249-0161 surname: Vitkov fullname: Vitkov, Ljubomir organization: Clinic of Operative Dentistry, Periodontology and Preventive Dentistry, Saarland University, Homburg, Germany – sequence: 42 givenname: Maren orcidid: 0000-0001-7712-9767 surname: von Köckritz-Blickwede fullname: von Köckritz-Blickwede, Maren organization: Institute for Biochemistry and Research Center for Emerging Infections and Zonoses, University of Veterinary Medicine Hannover, Hannover, Germany – sequence: 43 givenname: Cansu surname: Yanginlar fullname: Yanginlar, Cansu organization: Department of Nephrology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands – sequence: 44 givenname: Shida orcidid: 0000-0002-9855-4305 surname: Yousefi fullname: Yousefi, Shida organization: Institute of Pharmacology, University of Bern, Inselspital, INO-F, Bern, Switzerland – sequence: 45 givenname: Alexander surname: Zarbock fullname: Zarbock, Alexander organization: Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany – sequence: 46 givenname: Georg orcidid: 0000-0001-8740-9615 surname: Schett fullname: Schett, Georg organization: Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany – sequence: 47 givenname: Martin orcidid: 0000-0002-0258-2484 surname: Herrmann fullname: Herrmann, Martin email: martin.herrmann@uk-erlangen.de, martin.herrmann@uk-erlangen.de organization: Deutsches Zentrum für Immuntherapie (DZI), Friedrich-Alexander-University Erlangen-Nürnberg and Universitätsklinikum Erlangen, Erlangen, Germany. martin.herrmann@uk-erlangen.de
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PublicationTitle	Cell death and differentiation
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Snippet	SARS-CoV-2 infection poses a major threat to the lungs and multiple other organs, occasionally causing death. Until effective vaccines are developed to curb...
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SubjectTerms	Adaptive immunity Citrullination Complement Activation Coronaviruses COVID-19 COVID-19 - complications COVID-19 - immunology COVID-19 - pathology Extracellular Traps - metabolism Humans Immune response Inflammatory diseases Leukocytes (neutrophilic) Neutrophils Neutrophils - immunology Neutrophils - metabolism Pandemics Patients Platelet Activation SARS-CoV-2 - isolation & purification Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index Thrombosis - etiology
Title	Patients with COVID-19: in the dark-NETs of neutrophils
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