Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis.
Julien Carvelli,Olivier Demaria,Frédéric Vély,Luciana Batista,Nassima Chouaki Benmansour,Joanna Fares,Sabrina Carpentier,Marie-Laure Thibult,Ariane Morel,Romain Remark,Pascale Andre,Agnès Represa,Christelle Piperoglou,Pierre Yves Cordier,Erwan Le Dault,Christophe Guervilly,Pierre Simeone,Marc Gainnier,Yannis Morel,Mikael Ebbo,Nicolas Schleinitz,Eric Vivier +21 more
TLDR
Results suggest that blockade of the C5a–C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19.Abstract:
Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic1. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory responses by recruiting and activating neutrophils and monocytes1. Here we provide a longitudinal analysis of immune responses, including phenotypic analyses of immune cells and assessments of the soluble factors that are present in the blood and bronchoalveolar lavage fluid of patients at various stages of COVID-19 severity, including those who were paucisymptomatic or had pneumonia or acute respiratory distress syndrome. The levels of soluble C5a were increased in proportion to the severity of COVID-19 and high expression levels of C5aR1 receptors were found in blood and pulmonary myeloid cells, which supports a role for the C5a-C5aR1 axis in the pathophysiology of acute respiratory distress syndrome. Anti-C5aR1 therapeutic monoclonal antibodies prevented the C5a-mediated recruitment and activation of human myeloid cells, and inhibited acute lung injury in human C5aR1 knock-in mice. These results suggest that blockade of the C5a-C5aR1 axis could be used to limit the infiltration of myeloid cells in damaged organs and prevent the excessive lung inflammation and endothelialitis that are associated with acute respiratory distress syndrome in patients with COVID-19.read more
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Genetic mechanisms of critical illness in Covid-19.
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Thomson,Alfred A.R. Thompson,Ryan S Thwaites,L Turtle,Maria Zambon,Hayley Hardwick,Chloe Donohue,Ronan A Lyons,Lisa Norman,Riinu Pius,Thomas M Drake,Cameron J Fairfield,Stephen R Knight,Kenneth A. McLean,Derek Murphy,C. A. Shaw,Jo Dalton,Michelle Girvan,Egle Saviciute,Stuart K. Roberts,Janet Harrison,Laura Marsh,Marie Connor,Sophie Halpin,Carrol Gamble,Gary Leeming,Murray Wham,William Greenhalf,V. Shaw,Sarah D. McDonald,Andrea Ganna,Patrick Sulem,D A van Heel,M. Cordioli,Gardar Sveinbjornsson,M. E. K. Niemi,Janie F. Shelton,A. J. Shastri,C. Ye,C. H. Weldon,T. Filshtein-Sonmez,D. Coker,A. Symons,J. Esparza-Gordillo,Stella Aslibekyan,Adam Auton,J. E. Krieger,E. Marques,C. E. Jannes,Francesca Mari,S. Daga,Margherita Baldassarri,Elisa Benetti,Simone Furini,Chiara Fallerini,Francesca Fava,Floriana Valentino,G. Doddato,Annarita Giliberti,Rossella Tita,Sara Amitrano,Mirella Bruttini,S. Croci,I. Meloni,A. M. Pinto,E. Frullanti,Maria Antonietta Mencarelli,C. L. Rizzo,Francesca Montagnani,L. Di Sarno,A. Tommasi,Marta Palmieri,Arianna Emiliozzi,M. Fabbiani,Barbara Rossetti,Giacomo Zanelli,Elena Bargagli,Laura Bergantini,Miriana d'Alessandro,Paolo Cameli,D. Bennet,Federico Anedda,Simona Marcantonio,Sabino Scolletta,Federico Franchi,Maria Antonietta Mazzei,S. Guerrini,Edoardo Conticini,Luca Cantarini,Bruno Frediani,D. Tacconi,C. Spertilli,M. Feri,Abele Donati,R. Scala,L. Guidelli,G. Spargi,M. Corridi,C. Nencioni,L. Croci,G. P. Caldarelli,M. Spagnesi,P. Piacentini,M. Bandini,E. Desanctis,S. Cappelli,A. Canaccini,A. Verzuri,V. Anemoli,A. Ognibene,M. Vaghi,A d'Arminio Monforte,Esther Merlini,M. U. Mondelli,S. Mantovani,S. Ludovisi,Massimo Girardis,S. Venturelli,M. Sita,Andrea Cossarizza,A. Antinori,Alessandra Vergori,Stefano Rusconi,M. Siano,A. Gabrieli,Agostino Riva,Daniela Francisci,Elisabetta Schiaroli,P. G. Scotton,F. Andretta,S. Panese,R. Scaggiante,F. Gatti,S. G. Parisi,Francesco Castelli,M. E. Quiros-Roldan,P. Magro,Isabella Zanella,M. Della Monica,Carmelo Piscopo,Mario Capasso,Roberta Russo,Immacolata Andolfo,Achille Iolascon,G. Fiorentino,M. Carella,Marco Castori,Giuseppe Merla,Filippo Aucella,P. Raggi,C. Marciano,R. Perna,Matteo Bassetti,A. Di Biagio,M. Sanguinetti,L. Masucci,Serafina Valente,Marco Mandalà,A. Giorli,L. Salerni,P. Zucchi,P. Parravicini,E. Menatti,S. Baratti,T. Trotta,F. Giannattasio,G. Coiro,F. Lena,D. A. Coviello,Cristina Mussini,G. Bosio,E. Martinelli,Sandro Mancarella,L. Tavecchia,L. Crotti,N. Picchiotti,M. Gori,C. Gabbi,M. Sanarico,S. Ceri,P. Pinoli,F. Raimondi,F. Biscarini,A. Stella,Xia Shen,Xia Shen,Chris P. Ponting,Angie Fawkes,Albert Tenesa,Albert Tenesa,Mark J. Caulfield,Richard H Scott,K Rowan,Lee Murphy,Peter J. M. Openshaw,Peter J. M. Openshaw,Malcolm G Semple,Veronique Vitart,James F. Wilson +1449 more
TL;DR: The GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2244 critically ill Covid-19 patients from 208 UK intensive care units is reported, finding evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease.
Journal ArticleDOI
The COVID-19 puzzle: deciphering pathophysiology and phenotypes of a new disease entity.
Marcin F. Osuchowski,Martin Sebastian Winkler,Tomasz Skirecki,Sara Cajander,Manu Shankar-Hari,Manu Shankar-Hari,Gunnar Lachmann,Guillaume Monneret,Fabienne Venet,Michael Bauer,Frank M. Brunkhorst,Sebastian Weis,Alberto García-Salido,Matthijs Kox,Jean-Marc Cavaillon,Florian Uhle,Markus A. Weigand,Stefanie B. Flohé,W. Joost Wiersinga,Raquel Almansa,Amanda de la Fuente,Ignacio Martin-Loeches,Christian Meisel,Thibaud Spinetti,Joerg C. Schefold,Catia Cilloniz,Antoni Torres,Antoni Torres,Evangelos J. Giamarellos-Bourboulis,Ricard Ferrer,Ricard Ferrer,Massimo Girardis,Andrea Cossarizza,Mihai G. Netea,Mihai G. Netea,Mihai G. Netea,Tom van der Poll,Jesus F. Bermejo-Martin,Ignacio Rubio +38 more
TL;DR: The authors reviewed the intricacies of COVID-19 pathophysiology, its various phenotypes, and the anti-SARS-CoV-2 host response at the humoral and cellular levels.
Journal ArticleDOI
Systemic complement activation is associated with respiratory failure in COVID-19 hospitalized patients.
Jan Cato Holter,Jan Cato Holter,Soeren Erik Pischke,Soeren Erik Pischke,Eline de Boer,Eline de Boer,Andreas Lind,Synne Jenum,Aleksander Rygh Holten,Aleksander Rygh Holten,Kristian Tonby,Kristian Tonby,Andreas Barratt-Due,Andreas Barratt-Due,Marina Sokolova,Marina Sokolova,Camilla Schjalm,Camilla Schjalm,Viktoriia Chaban,Viktoriia Chaban,Anette Kolderup,Trung Tran,Torleif Tollefsrud Gjølberg,Torleif Tollefsrud Gjølberg,Linda Gail Skeie,Liv Hesstvedt,Vidar Ormåsen,Vidar Ormåsen,Børre Fevang,Cathrine Austad,Karl Erik Müller,Karl Erik Müller,Cathrine Fladeby,Mona Holberg-Petersen,Bente Halvorsen,Bente Halvorsen,Fredrik Müller,Fredrik Müller,Pål Aukrust,Pål Aukrust,Pål Aukrust,Susanne Gjeruldsen Dudman,Susanne Gjeruldsen Dudman,Thor Ueland,Thor Ueland,Thor Ueland,Jan Terje Andersen,Jan Terje Andersen,Fridtjof Lund-Johansen,Fridtjof Lund-Johansen,Lars Heggelund,Lars Heggelund,Anne Ma Dyrhol-Riise,Anne Ma Dyrhol-Riise,Tom Eirik Mollnes +54 more
TL;DR: In this paper, a prospective cohort study of 39 hospitalized coronavirus disease COVID-19 patients, the authors describe systemic complement activation and its association with development of respiratory failure.
Journal ArticleDOI
Tissue-specific Immunopathology in Fatal COVID-19.
David A. Dorward,Clark D Russell,In Hwa Um,Mustafa Elshani,Stuart D. Armstrong,Rebekah Penrice-Randal,Tracey Millar,Chris E B Lerpiniere,Giulia Tagliavini,Catherine Hartley,Nadine Randle,Naomi N. Gachanja,Philippe M D Potey,Xiaofeng Dong,Alison M Anderson,Victoria L Campbell,Alasdair J Duguid,Wael Al Qsous,Ralph BouHaidar,J Kenneth Baillie,Kevin Dhaliwal,William A Wallace,Christopher Bellamy,Sandrine Prost,Colin Smith,Julian A. Hiscox,Julian A. Hiscox,Julian A. Hiscox,David J. Harrison,Christopher D. Lucas +29 more
TL;DR: Tissue-specific immunopathology occurs in COVID-19, implicating a significant component of the immune-mediated, virus-independent immunopathologic process as a primary mechanism in severe disease.
Journal ArticleDOI
Microthrombi as a Major Cause of Cardiac Injury in COVID-19: A Pathologic Study.
Dario Pellegrini,Rika Kawakami,Giulio Guagliumi,Atsushi Sakamoto,Kenji Kawai,Andrea Gianatti,Ahmed Nasr,Robert Kutys,Liang Guo,Anne Cornelissen,Lara Faggi,Masayuki Mori,Yu Sato,Irene Pescetelli,Matteo Brivio,Maria Romero,Renu Virmani,Aloke V. Finn +17 more
TL;DR: In this article, Cardiac injury is common in patients who are hospitalized with coronavirus disease 2019 (COVID-19) and portends poorer prognosis and the mechanism and the type of myocardial damag...
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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
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STAR: ultrafast universal RNA-seq aligner
Alexander Dobin,Carrie A. Davis,Felix Schlesinger,Jorg Drenkow,Chris Zaleski,Sonali Jha,Philippe Batut,Mark Chaisson,Thomas R. Gingeras +8 more
TL;DR: The Spliced Transcripts Alignment to a Reference (STAR) software based on a previously undescribed RNA-seq alignment algorithm that uses sequential maximum mappable seed search in uncompressed suffix arrays followed by seed clustering and stitching procedure outperforms other aligners by a factor of >50 in mapping speed.
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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.
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featureCounts: an efficient general-purpose program for assigning sequence reads to genomic features
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COVID-19: consider cytokine storm syndromes and immunosuppression
Puja Mehta,Daniel F. McAuley,Michael Brown,Emilie Sanchez,Rachel Tattersall,Rachel Tattersall,Jessica J Manson +6 more
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