Single-cell multi-omics analysis of the immune response in COVID-19.
Emily Stephenson,Gary Reynolds,Rachel A. Botting,Fernando J Calero-Nieto,Michael D Morgan,Michael D Morgan,Zewen K. Tuong,Zewen K. Tuong,Karsten Bach,Karsten Bach,Waradon Sungnak,Kaylee B Worlock,Masahiro Yoshida,Natsuhiko Kumasaka,Katarzyna D. Kania,Justin Engelbert,Bayanne Olabi,Jarmila Stremenova Spegarova,Nicola K. Wilson,Nicole Mende,Laura Jardine,Louis C.S. Gardner,Issac Goh,Dave Horsfall,Jim McGrath,Simone Webb,Michael W. Mather,Rik G.H. Lindeboom,Emma Dann,Ni Huang,Krzysztof Polanski,Elena Prigmore,Florian Gothe,Florian Gothe,Jonathan M. Scott,Rebecca Payne,Kenneth F Baker,Kenneth F Baker,Aidan T Hanrath,Aidan T Hanrath,Ina Schim van der Loeff,Andrew Barr,Amada Sanchez-Gonzalez,Laura Bergamaschi,Federica Mescia,Josephine Barnes,Eliz Kilich,Angus de Wilton,A Saigal,Aarash Saleh,Sam M. Janes,Sam M. Janes,Claire Smith,Nusayhah Gopee,Caroline Wilson,Caroline Wilson,Paul Coupland,Jonathan Coxhead +57 more
TLDR
In this article, the authors performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19.Abstract:
Analysis of human blood immune cells provides insights into the coordinated response to viral infections such as severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019 (COVID-19). We performed single-cell transcriptome, surface proteome and T and B lymphocyte antigen receptor analyses of over 780,000 peripheral blood mononuclear cells from a cross-sectional cohort of 130 patients with varying severities of COVID-19. We identified expansion of nonclassical monocytes expressing complement transcripts (CD16+C1QA/B/C+) that sequester platelets and were predicted to replenish the alveolar macrophage pool in COVID-19. Early, uncommitted CD34+ hematopoietic stem/progenitor cells were primed toward megakaryopoiesis, accompanied by expanded megakaryocyte-committed progenitors and increased platelet activation. Clonally expanded CD8+ T cells and an increased ratio of CD8+ effector T cells to effector memory T cells characterized severe disease, while circulating follicular helper T cells accompanied mild disease. We observed a relative loss of IgA2 in symptomatic disease despite an overall expansion of plasmablasts and plasma cells. Our study highlights the coordinated immune response that contributes to COVID-19 pathogenesis and reveals discrete cellular components that can be targeted for therapy.read more
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Journal ArticleDOI
Multiple early factors anticipate post-acute COVID-19 sequelae
Yapeng Su,Dan Yuan,Daniel G. Chen,Rachel Ng,Kai Wang,Jongchan Choi,Sarah Li,Sunga Hong,Rongyu Zhang,Jingyi Xie,Sergey A. Kornilov,Kelsey Scherler,A.-J. Pavlovitch-Bedzyk,Shen Dong,Christopher Lausted,Inyoul Lee,Shannon Fallen,Chengzhen L. Dai,Priyanka Baloni,Brett Smith,Venkata R. Duvvuri,Kristin G. Anderson,Jing Wei Li,Fan Yang,Caroline J. Duncombe,Denise J. McCulloch,Clifford Rostomily,Pamela Troisch,Jing Zhou,Sean Mackay,Quinn DeGottardi,Damon May,Ruth T. Taniguchi,Rachel M. Gittelman,Mark Klinger,Thomas M. Snyder,Ryan Roper,Gladys Wojciechowska,Kim Murray,Rick Edmark,Simon Evans,Lesley Jones,Yon-gan Zhou,Lee Rowen,Rachel Xia-Ying Liu,William Chour,Heather Algren,William R. Berrington,Julie A. Wallick,Rebecca Cochran,Mary Micikas,Christos J. Petropoulos,Hunter Cole,Trevan D Fischer,Wei Wei,Dave S.B. Hoon,Nathan D. Price,Naeha Subramanian,Joshua A. Hill,Jenn J. Hadlock,Andrew T. Magis,Antoni Ribas,Lewis L. Lanier,Scott D. Boyd,Jeffrey A. Bluestone,Helen Y. Chu,Leroy Hood,Raphael Gottardo,Philip D. Greenberg,Mark M. Davis,Jason D Goldman,James R. Heath +71 more
TL;DR: Huang et al. as discussed by the authors performed a deep multi-omic, longitudinal investigation of 309 COVID-19 patients from initial diagnosis to convalescence (2-3 months later), integrated with clinical data and patient-reported symptoms.
Journal ArticleDOI
Systems vaccinology of the BNT162b2 mRNA vaccine in humans.
Prabhu S. Arunachalam,Madeleine K D Scott,Thomas Hagan,Thomas Hagan,Chunfeng Li,Yupeng Feng,Florian Wimmers,Lilit Grigoryan,Meera Trisal,Venkata Viswanadh Edara,Lilin Lai,Sarah Esther Chang,Allan Feng,Shaurya Dhingra,Mihir Shah,Alexandra S. Lee,Sharon Chinthrajah,Sayantani B. Sindher,Vamsee Mallajosyula,Fei Gao,Natalia Sigal,Sangeeta Kowli,Sheena Gupta,Kathryn L. Pellegrini,Gregory K. Tharp,Sofia Maysel-Auslender,Sydney Hamilton,Hadj Aoued,Kevin Hrusovsky,Mark Roskey,Steven E. Bosinger,Steven E. Bosinger,Holden T. Maecker,Scott D. Boyd,Mark M. Davis,Paul J. Utz,Mehul S. Suthar,Purvesh Khatri,Kari C. Nadeau,Kari C. Nadeau,Bali Pulendran +40 more
TL;DR: In this article, the authors used a system vaccinology approach to comprehensively profile the innate and adaptive immune responses of 56 healthy volunteers who were vaccinated with the Pfizer-BioNTech mRNA vaccine (BNT162b2).
Journal ArticleDOI
Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19.
Monique G. P. van der Wijst,Sara E. Vazquez,George C. Hartoularos,Paul Bastard,Tianna Grant,Raymund Bueno,David Lee,John R. Greenland,Yang Sun,Richard Perez,Richard Perez,Anton Ogorodnikov,Anton Ogorodnikov,Alyssa Ward,Sabrina A Mann,Kara L. Lynch,Cassandra Yun,Diane V. Havlir,Gabriel Chamie,Carina Marquez,Bryan Greenhouse,Michail S. Lionakis,Philip J. Norris,Larry J. Dumont,Kathleen Kelly,Peng Zhang,Qian Zhang,Adrian Gervais,Adrian Gervais,Tom Le Voyer,Tom Le Voyer,Alexander Whatley,Yichen Si,Ashley Byrne,Alexis J. Combes,Arjun A. Rao,Yun S. Song,Gabriela K. Fragiadakis,Kirsten N. Kangelaris,Carolyn S. Calfee,David J. Erle,Carolyn M. Hendrickson,Matthew F. Krummel,Matthew F. Krummel,Prescott G. Woodruff,Charles Langelier,Jean-Laurent Casanova,Joseph L. DeRisi,Mark S. Anderson,Chun Jimmie Ye +49 more
TL;DR: In this article, the authors found no type I IFN autoantibodies in individuals with moderate disease and no IFN-stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease.
Journal ArticleDOI
Monocytes and Macrophages in COVID-19.
TL;DR: In this article, the authors outline current knowledge on monocytes and macrophages in homeostasis and viral infections and summarize concepts and key findings on their role in COVID-19.
Journal ArticleDOI
Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.
Benjamin Krämer,Rainer Knoll,Lorenzo Bonaguro,Michael ToVinh,Jan Raabe,Rosario Astaburuaga-García,Jonas Schulte-Schrepping,Kim Melanie Kaiser,Gereon Rieke,Jenny Bischoff,Malte B Monin,Christoph Hoffmeister,S Schlabe,Elena De Domenico,Nico Reusch,Kristian Händler,Gary Reynolds,Nils Blüthgen,Gudrun Hack,Claudia Finnemann,Hans Dieter Nischalke,Christian P. Strassburg,Emily Stephenson,Yapeng Su,Louis C.S. Gardner,Dan Yuan,Daniel Chen,Jason Goldman,P Rosenstiel,Susanne Schmidt,Eicke Latz,Kevin Hrusovsky,Andrew J. Ball,Joseph M. Johnson,Paul-Albert Koenig,Florian I. Schmidt,Muzlifah Haniffa,James R. Heath,Beate M. Kümmerer,Verena Keitel,Björn Jensen,Paula Stubbemann,Florian Kurth,Leif E. Sander,Birgit Sawitzki,Anna C. Aschenbrenner,Joachim L. Schultze,Jacob Nattermann +47 more
TL;DR: In this article, the authors performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies.
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