A single-cell atlas of the peripheral immune response in patients with severe COVID-19.
Aaron J. Wilk,Arjun Rustagi,Nancy Q. Zhao,Jonasel Roque,Giovanny J Martínez-Colón,Julia L. McKechnie,Geoffrey T. Ivison,Thanmayi Ranganath,Rosemary Vergara,Taylor Mi Hollis,Laura J. Simpson,Philip M. Grant,Aruna Subramanian,Albert J. Rogers,Catherine A. Blish +14 more
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TLDR
Single-cell transcriptomic analysis identifies changes in peripheral immune cells in seven hospitalized patients with COVID-19, including HLA class II downregulation, a heterogeneous interferon-stimulated gene signature and low pro-inflammatory cytokine gene expression in monocytes and lymphocytes.Abstract:
There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide1. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care2. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines3,4 that may be produced by a subset of inflammatory monocytes5,6, lymphopenia7,8 and T cell exhaustion9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.read more
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Integrated analysis of multimodal single-cell data
Yuhan Hao,Stephanie Hao,Erica Andersen-Nissen,William M. Mauck,Shiwei Zheng,Andrew Butler,Maddie Jane Lee,Aaron J. Wilk,Charlotte A. Darby,Michael Zager,Paul Hoffman,Marlon Stoeckius,Efthymia Papalexi,Eleni P. Mimitou,Jaison Jain,Avi Srivastava,Tim Stuart,Lamar M. Fleming,Bertrand Z. Yeung,Angela J. Rogers,Juliana M. McElrath,Catherine A. Blish,Raphael Gottardo,Peter Smibert,Rahul Satija +24 more
TL;DR: Weighted-nearest neighbor analysis as mentioned in this paper is an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities.
Posted ContentDOI
Integrated analysis of multimodal single-cell data
Yuhan Hao,Stephanie Hao,Erica Andersen-Nissen,William M. Mauck,Shiwei Zheng,Andrew Butler,Maddie Jane Lee,Aaron J. Wilk,Charlotte A. Darby,Michael Zagar,Paul Hoffman,Marlon Stoeckius,Efthymia Papalexi,Eleni P. Mimitou,Jaison Jain,Avi Srivastava,Tim Stuart,Lamar Ballweber Fleming,Bertrand Z. Yeung,Angela J. Rogers,Juliana M. McElrath,Catherine A. Blish,Raphael Gottardo,Peter Smibert,Rahul Satija +24 more
TL;DR: ‘weighted-nearest neighbor’ analysis is introduced, an unsupervised framework to learn the relative utility of each data type in each cell, enabling an integrative analysis of multiple modalities.
Journal ArticleDOI
Robust T Cell Immunity in Convalescent Individuals with Asymptomatic or Mild COVID-19.
Takuya Sekine,André Perez-Potti,Olga Rivera-Ballesteros,Kristoffer Strålin,Jean Baptiste Gorin,Annika Olsson,Sian Llewellyn-Lacey,Habiba Kamal,Gordana Bogdanovic,Sandra Muschiol,David J. Wullimann,Tobias Kammann,Johanna Emgård,Tiphaine Parrot,Elin Folkesson,Olav Rooyackers,Lars Eriksson,Jan-Inge Henter,Anders Sönnerborg,Tobias Allander,Jan Albert,Morten Nielsen,Jonas Klingström,Sara Gredmark-Russ,Niklas K. Björkström,Johan K. Sandberg,David Price,Hans-Gustaf Ljunggren,Soo Aleman,Marcus Buggert +29 more
TL;DR: It is shown that SARS-CoV-2 elicits robust, broad and highly functional memory T cell responses, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19.
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
Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans.
Prabhu S. Arunachalam,Florian Wimmers,Chris Ka Pun Mok,Ranawaka A.P.M. Perera,Madeleine K D Scott,Thomas Hagan,Natalia Sigal,Yupeng Feng,Laurel Bristow,Owen Tak-Yin Tsang,Dhananjay Wagh,John A. Coller,Kathryn L. Pellegrini,Dmitri Kazmin,Ghina Alaaeddine,Wai Shing Leung,Jacky Man Chun Chan,Thomas Shiu Hong Chik,Chris Yau Chung Choi,Christopher Huerta,Michele Paine McCullough,Huibin Lv,Evan J. Anderson,Srilatha Edupuganti,Amit A. Upadhyay,Steve E. Bosinger,Steve E. Bosinger,Holden T. Maecker,Purvesh Khatri,Nadine Rouphael,Malik Peiris,Bali Pulendran +31 more
TL;DR: In the peripheral blood mononuclear cells of COVID-19 patients, the authors observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon-α (IFN-α) production by plasmacytoid dendritic cells.
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