Targeting potential drivers of COVID-19: Neutrophil extracellular traps.
Betsy J. Barnes,José M. Adrover,Amelia Baxter-Stoltzfus,Alain C. Borczuk,Jonathan Cools-Lartigue,James M. Crawford,Juliane Daßler-Plenker,Philippe Guerci,Caroline Huynh,Jason S. Knight,Massimo Loda,Mark R. Looney,Florencia McAllister,Roni F. Rayes,Stéphane Renaud,Simon Rousseau,Steven P. Salvatore,Robert E. Schwartz,Jonathan Spicer,Christian C. Yost,Andrew G. Weber,Yu Zuo,Mikala Egeblad +22 more
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TLDR
Autopsy results and literature are presented supporting the hypothesis that neutrophil extracellular traps (NETs) may contribute to organ damage and mortality in COVID-19, and existing drugs that target NETs, although unspecific, may benefit CO VID-19 patients.Abstract:
Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10-15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils-the ability to form neutrophil extracellular traps (NETs)-may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.read more
Citations
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Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study
Fei Zhou,Ting Yu,Ronghui Du,Guohui Fan,Ying Liu,Zhibo Liu,Jie Xiang,Yeming Wang,Bin Song,Xiaoying Gu,Xiaoying Gu,Lulu Guan,Yuan Wei,Li Hui,Xudong Wu,Jiuyang Xu,Shengjin Tu,Yi Zhang,Hua Chen,Bin Cao +19 more
TL;DR: Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.
Journal ArticleDOI
Immunology of COVID-19: Current State of the Science.
Nicolas Vabret,Graham J. Britton,Conor Gruber,Samarth Hegde,Joel Kim,Maria Kuksin,Rachel Levantovsky,Louise Malle,Alvaro Moreira,Matthew D. Park,Luisanna Pia,Emma Risson,Miriam Saffern,Bérengère Salomé,Myvizhi Esai Selvan,Matthew P. Spindler,Jessica Tan,Verena van der Heide,Jill Gregory,Konstantina Alexandropoulos,Nina Bhardwaj,Brian D. Brown,Benjamin Greenbaum,Zeynep H. Gümüş,Dirk Homann,Amir Horowitz,Alice O. Kamphorst,Maria A. Curotto de Lafaille,Saurabh Mehandru,Miriam Merad,Robert M. Samstein,Manasi Agrawal,Mark Aleynick,Meriem Belabed,Matthew Brown,Maria Casanova-Acebes,Jovani Catalan,Monica Centa,Andrew Charap,Andrew K Chan,Steven T. Chen,Jonathan Chung,Cansu Cimen Bozkus,Evan Cody,Francesca Cossarini,Erica Dalla,Nicolas F. Fernandez,John A. Grout,Dan Fu Ruan,Pauline Hamon,Etienne Humblin,Divya Jha,Julia Kodysh,Andrew Leader,Matthew Lin,Katherine E. Lindblad,Daniel Lozano-Ojalvo,Gabrielle Lubitz,Assaf Magen,Zafar Mahmood,Gustavo Martinez-Delgado,Jaime Mateus-Tique,Elliot Meritt,Chang Moon,Justine Noel,Timothy O'Donnell,Miyo Ota,Tamar Plitt,Venu Pothula,Jamie Redes,Ivan Reyes Torres,Mark P. Roberto,Alfonso R. Sanchez-Paulete,Joan Shang,Alessandra Soares Schanoski,Maria Suprun,Michelle Tran,Natalie Vaninov,C. Matthias Wilk,Julio A. Aguirre-Ghiso,Dusan Bogunovic,Judy H. Cho,Jeremiah J. Faith,Emilie K. Grasset,Peter S. Heeger,Ephraim Kenigsberg,Florian Krammer,Uri Laserson +87 more
TL;DR: The current state of knowledge of innate and adaptive immune responses elicited by SARS-CoV-2 infection and the immunological pathways that likely contribute to disease severity and death are summarized.
Journal ArticleDOI
Neutrophil extracellular traps in COVID-19.
Yu Zuo,Srilakshmi Yalavarthi,Hui Shi,Hui Shi,Kelsey Gockman,Melanie Zuo,Jacqueline A. Madison,Christopher N. Blair,Andrew G. Weber,Betsy J. Barnes,Betsy J. Barnes,Mikala Egeblad,Robert J. Woods,Yogendra Kanthi,Jason S. Knight +14 more
TL;DR: Sera from patients with COVID-19 have elevated levels of cell-free DNA, myeloperoxidase(MPO)-DNA, and citrullinated histone H3 (Cit-H3); the latter two are highly specific markers of NETs, which may contribute to cytokine release and respiratory failure.
Journal ArticleDOI
Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment.
Jonas Schulte-Schrepping,Nico Reusch,Daniela Paclik,Kevin Baßler,Stephan Schlickeiser,Bowen Zhang,Benjamin Krämer,Tobias Krammer,Sophia Brumhard,Lorenzo Bonaguro,Elena De Domenico,Daniel Wendisch,Martin Grasshoff,Theodore S. Kapellos,Michael Beckstette,Tal Pecht,Adem Saglam,Oliver Dietrich,Henrik E. Mei,Axel Schulz,Claudia Conrad,Désirée Kunkel,Ehsan Vafadarnejad,Cheng-Jian Xu,Cheng-Jian Xu,Arik Horne,Miriam Herbert,Anna Drews,Charlotte Thibeault,Moritz Pfeiffer,Stefan Hippenstiel,Andreas C. Hocke,Holger Müller-Redetzky,Katrin-Moira Heim,Felix Machleidt,Alexander Uhrig,Laure Bosquillon de Jarcy,Linda Jürgens,Miriam Stegemann,Christoph R. Glösenkamp,Hans-Dieter Volk,Christine Goffinet,Markus Landthaler,Emanuel Wyler,Philipp Georg,Maria Schneider,Chantip Dang-Heine,Nick Neuwinger,Kai Kappert,Rudolf Tauber,Victor M. Corman,Jan Raabe,Kim Melanie Kaiser,Michael To Vinh,Gereon Rieke,Christian Meisel,Thomas Ulas,Matthias Becker,Robert Geffers,Martin Witzenrath,Christian Drosten,Norbert Suttorp,Christof von Kalle,Florian Kurth,Florian Kurth,Florian Kurth,Kristian Händler,Joachim L. Schultze,Joachim L. Schultze,Anna C. Aschenbrenner,Anna C. Aschenbrenner,Yang Li,Yang Li,Jacob Nattermann,Birgit Sawitzki,Antoine-Emmanuel Saliba,Leif E. Sander,Angel Angelov,Robert Bals,Alexander Bartholomäus,Anke Becker,Daniela Bezdan,Ezio Bonifacio,Peer Bork,Thomas Clavel,Maria Colomé-Tatché,Andreas Diefenbach,Alexander T. Dilthey,Nicole Fischer,Konrad U. Förstner,Julia-Stefanie Frick,Julien Gagneur,Alexander Goesmann,Torsten Hain,Michael Hummel,Stefan Janssen,Jörn Kalinowski,René Kallies,Birte Kehr,Andreas Keller,Sarah Kim-Hellmuth,Christoph Klein,Oliver Kohlbacher,Jan O. Korbel,Ingo Kurth,Kerstin U. Ludwig,Oliwia Makarewicz,Manja Marz,Alice C. McHardy,Christian Mertes,Markus M. Nöthen,Peter Nürnberg,Uwe Ohler,Stephan Ossowski,Jörg Overmann,Silke Peter,Klaus Pfeffer,Anna R. Poetsch,Alfred Pühler,Nikolaus Rajewsky,Markus Ralser,Olaf Rieß,Stephan Ripke,Ulisses Nunes da Rocha,Philip Rosenstiel,Philipp H. Schiffer,Eva-Christina Schulte,Alexander Sczyrba,Oliver Stegle,Jens Stoye,Fabian J. Theis,Janne Vehreschild,Jörg Vogel,Max von Kleist,Andreas Walker,Jörn Walter,Dagmar Wieczorek,John Ziebuhr +137 more
TL;DR: This study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.
Journal ArticleDOI
Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome.
Elizabeth A. Middleton,Xue-Yan He,Frederik Denorme,Robert A. Campbell,David Ng,Steven P. Salvatore,Steven P. Salvatore,Maria Mostyka,Amelia Baxter-Stoltzfus,Alain C. Borczuk,Alain C. Borczuk,Massimo Loda,Massimo Loda,Mark J. Cody,Bhanu Kanth Manne,Irina Portier,Estelle S. Harris,Aaron C. Petrey,Ellen J. Beswick,Aleah F. Caulin,Anthony J. Iovino,Lisa M. Abegglen,Andrew S. Weyrich,Matthew T. Rondina,Mikala Egeblad,Joshua D. Schiffman,Christian C. Yost +26 more
TL;DR: NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.
References
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Journal ArticleDOI
Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
Chaolin Huang,Yeming Wang,Xingwang Li,Lili Ren,Jianping Zhao,Yi Hu,Li Zhang,Guohui Fan,Jiuyang Xu,Xiaoying Gu,Zhenshun Cheng,Ting Yu,Jia'an Xia,Yuan Wei,Wenjuan Wu,Xuelei Xie,Wen Yin,Li Hui,Min Liu,Yan Xiao,Hong Gao,Li Guo,Jungang Xie,Guang-Fa Wang,Rongmeng Jiang,Zhancheng Gao,Qi Jin,Jianwei Wang,Bin Cao +28 more
TL;DR: The epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of patients with laboratory-confirmed 2019-nCoV infection in Wuhan, China, were reported.
Journal ArticleDOI
Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.
Fei Zhou,Ting Yu,Ronghui Du,Guohui Fan,Ying Liu,Zhibo Liu,Jie Xiang,Yeming Wang,Bin Song,Xiaoying Gu,Xiaoying Gu,Lulu Guan,Yuan Wei,Li Hui,Xudong Wu,Jiuyang Xu,Shengjin Tu,Yi Zhang,Hua Chen,Bin Cao +19 more
TL;DR: Wang et al. as discussed by the authors used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death, including older age, high SOFA score and d-dimer greater than 1 μg/mL.
Journal ArticleDOI
Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China.
Dawei Wang,Bo Hu,Chang Hu,Fangfang Zhu,Xing Liu,Jing Zhang,Binbin Wang,Hui Xiang,Zhenshun Cheng,Yong Xiong,Yan Zhao,Yirong Li,Xinghuan Wang,Zhiyong Peng +13 more
TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Journal ArticleDOI
Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study
Nanshan Chen,Min Zhou,Xuan Dong,Jie-Ming Qu,Fengyun Gong,Yang Han,Yang Qiu,Jingli Wang,Ying Liu,Yuan Wei,Jia'an Xia,Ting Yu,Xinxin Zhang,Li Zhang +13 more
TL;DR: Characteristics of patients who died were in line with the MuLBSTA score, an early warning model for predicting mortality in viral pneumonia, and further investigation is needed to explore the applicability of the Mu LBSTA scores in predicting the risk of mortality in 2019-nCoV infection.
Journal ArticleDOI
Neutrophil extracellular traps kill bacteria
Volker Brinkmann,Ulrike Reichard,Christian Goosmann,Beatrix Fauler,Yvonne Uhlemann,David S. Weiss,Yvette Weinrauch,Yvette Weinrauch,Arturo Zychlinsky +8 more
TL;DR: It is described that, upon activation, neutrophils release granule proteins and chromatin that together form extracellular fibers that bind Gram-positive and -negative bacteria, which degrade virulence factors and kill bacteria.
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