COVID-19 severity correlates with airway epithelium-immune cell interactions identified by single-cell analysis.
Robert Lorenz Chua,Soeren Lukassen,Saskia Trump,Bianca P Hennig,Daniel Wendisch,Fabian Pott,Olivia Debnath,Loreen Thürmann,Florian Kurth,Florian Kurth,Maria Theresa Völker,Julia Kazmierski,Bernd Timmermann,Sven Twardziok,Stefan Schneider,Felix Machleidt,Holger Müller-Redetzky,Melanie Maier,Alexander Krannich,Sein Schmidt,Felix Balzer,Johannes Liebig,Jennifer Loske,Norbert Suttorp,Jürgen Eils,Naveed Ishaque,Uwe G. Liebert,Christof von Kalle,Andreas C. Hocke,Martin Witzenrath,Christine Goffinet,Christian Drosten,Sven Laudi,Irina Lehmann,Christian Conrad,Leif E. Sander,Roland Eils,Roland Eils +37 more
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The data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19, which likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure.Abstract:
To investigate the immune response and mechanisms associated with severe coronavirus disease 2019 (COVID-19), we performed single-cell RNA sequencing on nasopharyngeal and bronchial samples from 19 clinically well-characterized patients with moderate or critical disease and from five healthy controls We identified airway epithelial cell types and states vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection In patients with COVID-19, epithelial cells showed an average three-fold increase in expression of the SARS-CoV-2 entry receptor ACE2, which correlated with interferon signals by immune cells Compared to moderate cases, critical cases exhibited stronger interactions between epithelial and immune cells, as indicated by ligand-receptor expression profiles, and activated immune cells, including inflammatory macrophages expressing CCL2, CCL3, CCL20, CXCL1, CXCL3, CXCL10, IL8, IL1B and TNF The transcriptional differences in critical cases compared to moderate cases likely contribute to clinical observations of heightened inflammatory tissue damage, lung injury and respiratory failure Our data suggest that pharmacologic inhibition of the CCR1 and/or CCR5 pathways might suppress immune hyperactivation in critical COVID-19read more
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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
T cell responses in patients with COVID-19.
Zeyu Chen,E. John Wherry +1 more
TL;DR: Early reports of the T cell responses observed in patients with COVID-19 are summarized, emphasizing how different immune response characteristics in different patients may reflect a spectrum of disease phenotypes.
Journal ArticleDOI
SARS-CoV-2 infection of human ACE2-transgenic mice causes severe lung inflammation and impaired function.
Emma S. Winkler,Adam L. Bailey,Natasha M. Kafai,Sharmila Nair,Broc T. McCune,Jinsheng Yu,Julie M. Fox,Rita E. Chen,James T. Earnest,Shamus P. Keeler,Jon H. Ritter,Liang I. Kang,Sarah Dort,Annette Robichaud,Richard D. Head,Michael J. Holtzman,Michael S. Diamond +16 more
TL;DR: The transgenic mice expressing the human angiotensin I-converting enzyme 2 (ACE2) receptor driven by the cytokeratin-18 (K18) gene promoter are evaluated as a model of SARS-CoV-2 infection to define the basis of lung disease and test immune and antiviral-based countermeasures.
Journal ArticleDOI
Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19.
Jeong Seok Lee,Seongwan Park,Hye Won Jeong,Jin Young Ahn,Seong Jin Choi,Ho-Young Lee,Baekgyu Choi,Su Kyung Nam,Moa Sa,Ji Soo Kwon,Ji Soo Kwon,Su Jin Jeong,Heung Kyu Lee,Sung Ho Park,Su-Hyung Park,Jun Yong Choi,Sung-Han Kim,Inkyung Jung,Eui-Cheol Shin +18 more
TL;DR: It is proposed that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.
Journal ArticleDOI
Deciphering cell-cell interactions and communication from gene expression.
TL;DR: This Review highlights discoveries enabled by analyses of cell–cell interactions from transcriptomic data and reviews the methods and tools used in this context.
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SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor
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Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention
Zunyou Wu,Jennifer M. McGoogan +1 more
TL;DR: Hospitalised COVID-19 patients are frequently elderly subjects with co-morbidities receiving polypharmacy, all of which are known risk factors for d
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