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; Zewen Kelvin Tuong; Karsten Bach; Waradon Sungnak; Kaylee B. Worlock; Masahiro Yoshida; Natsuhiko Kumasaka; Katarzyna Kania; Justin Engelbert; Bayan 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; Jonathan Scott; Rebecca P. Payne; Kenneth F. Baker; Aidan T. Hanrath; Ina C. D. Schim van der Loeff; Andrew S. Barr; Amada Sanchez-Gonzalez; Laura Bergamaschi; Federica Mescia; Josephine L. Barnes; Eliz Kilich; Angus de Wilton; Anita Saigal; Aarash Saleh; Sam M. Janes; Claire M. Smith; Nusayhah Gopee; Caroline Wilson; Paul Coupland; Jonathan M. Coxhead; Vladimir Yu Kiselev; Stijn van Dongen; Jaume Bacardit; Hamish W. King; Anthony J. Rostron; A. John Simpson; Sophie Hambleton; Elisa Laurenti; Paul A. Lyons; Kerstin B. Meyer; Marko Z. Nikolic; Christopher J. A. Duncan; Kenneth G. C. Smith; Sarah A. Teichmann; Menna R. Clatworthy; John C. Marioni; Berthold Gottgens; Muzlifah Haniffa; Cambridge Inst Therapeutic Immunol; Paul Andrew Townsend

doi:10.1038/s41591-021-01329-2

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Single-cell multi-omics analysis of the immune response in COVID-19

Journal article

Open access

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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, Zewen Kelvin Tuong, Karsten Bach, Waradon Sungnak, Kaylee B. Worlock, Masahiro Yoshida, …

Nature medicine, Vol.27(5), pp.904-916

01/05/2021

DOI: https://doi.org/10.1038/s41591-021-01329-2

PMID: 33879890

Abstract

Biochemistry & Molecular Biology

Life Sciences & Biomedicine

Medicine, Research & Experimental

Research & Experimental Medicine

Science & Technology

Cell Biology

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. Transcriptomic and proteomic profiling of blood samples from individuals with COVID-19 reveals immune cell and hematopoietic progenitor cell alterations that are differentially associated with disease severity.

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Title: Single-cell multi-omics analysis of the immune response in COVID-19
Creators: Emily Stephenson - Newcastle University
Gary Reynolds - Newcastle University
Rachel A. Botting - Newcastle University
Fernando J. Calero-Nieto - Wellcome/MRC Cambridge Stem Cell Institute
Michael D. Morgan - European Bioinformatics Institute
Zewen Kelvin Tuong - University of Cambridge
Karsten Bach - European Bioinformatics Institute
Waradon Sungnak - Wellcome Sanger Institute
Kaylee B. Worlock - University College London
Masahiro Yoshida - University College London
Natsuhiko Kumasaka - Wellcome Sanger Institute
Katarzyna Kania - Cancer Research UK
Justin Engelbert - Newcastle University
Bayan Olabi - Newcastle Univ, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England
Jarmila Stremenova Spegarova - Newcastle University
Nicola K. Wilson - Wellcome/MRC Cambridge Stem Cell Institute
Nicole Mende - Wellcome/MRC Cambridge Stem Cell Institute
Laura Jardine - Newcastle University
Louis C. S. Gardner - Newcastle Univ, Biosci Inst, Newcastle Upon Tyne, Tyne & Wear, England
Issac Goh - Newcastle University
Dave Horsfall - Newcastle University
Jim McGrath - Newcastle University
Simone Webb - Newcastle University
Michael W. Mather - Newcastle University
Rik G. H. Lindeboom - Wellcome Sanger Institute
Emma Dann - Wellcome Sanger Institute
Ni Huang - Wellcome Sanger Institute
Krzysztof Polanski - Wellcome Sanger Institute
Elena Prigmore - Wellcome Sanger Institute
Florian Gothe - Newcastle University
Jonathan Scott - Newcastle University
Rebecca P. Payne - Newcastle University
Kenneth F. Baker - Newcastle University
Aidan T. Hanrath - Newcastle University
Ina C. D. Schim van der Loeff - Newcastle University
Andrew S. Barr - Newcastle upon Tyne Hospitals NHS Foundation Trust
Amada Sanchez-Gonzalez - Newcastle upon Tyne Hospitals NHS Foundation Trust
Laura Bergamaschi - University of Cambridge
Federica Mescia - University of Cambridge
Josephine L. Barnes - University College London
Eliz Kilich - University College London Hospitals NHS Foundation Trust
Angus de Wilton - University College London Hospitals NHS Foundation Trust
Anita Saigal - Royal Free London NHS Foundation Trust
Aarash Saleh - Royal Free London NHS Foundation Trust
Sam M. Janes - University College London
Claire M. Smith - Great Ormond Street Hospital
Nusayhah Gopee - Newcastle University
Caroline Wilson - Newcastle University
Paul Coupland - Cancer Research UK
Jonathan M. Coxhead - Newcastle University
Vladimir Yu Kiselev - Wellcome Sanger Institute
Stijn van Dongen - Wellcome Sanger Institute
Jaume Bacardit - Newcastle University
Hamish W. King - Wellcome Sanger Institute
Anthony J. Rostron - Newcastle University
A. John Simpson - Newcastle University
Sophie Hambleton - Newcastle University
Elisa Laurenti - Wellcome/MRC Cambridge Stem Cell Institute
Paul A. Lyons - University of Cambridge
Kerstin B. Meyer - Wellcome Sanger Institute
Marko Z. Nikolic - University College London
Christopher J. A. Duncan - University of Newcastle Australia
Kenneth G. C. Smith - University of Cambridge
Sarah A. Teichmann - Wellcome Sanger Institute
Menna R. Clatworthy - University of Cambridge
John C. Marioni - European Bioinformatics Institute
Berthold Gottgens - Wellcome/MRC Cambridge Stem Cell Institute
Muzlifah Haniffa - Newcastle University
Cambridge Inst Therapeutic Immunol
Paul Andrew Townsend - Faculty of Health and Medical Sciences
Publication Details: Nature medicine, Vol.27(5), pp.904-916
Publisher: NATURE PORTFOLIO
Number of pages: 41
Date published: 01/05/2021
Grant note: BB/V006738/1; BB/P002293/1 / BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) Newcastle NIHR Biomedical Research Centre Jikei University School of Medicine; Jikei University 203151/Z/16/Z; MR/S036113/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) ME 5209/11 / DFG Research Fellowship; German Research Foundation (DFG) WT206194 / Sanger Core University College London, Birkbeck MRC Doctoral Training Programme.; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) MR/S035842/1 / Medical Research Council Human Cell Atlas Research Grant MR/W014556/1; MR/S036113/1 / MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) ACF-2018-01-004 / NIHR; National Institutes of Health Research (NIHR) 107630/Z/15/Z; 213555/Z/18/Z; 212516/Z/18/Z; 211153/Z/18/Z / Wellcome Trust 213555/Z/18/Z / Sir Henry Wellcome Postdoctoral Fellowship; Wellcome Trust MR/5005579/1 / UK Regenerative Medicine Platform NIHR GOSH Biomedical research centre MRC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC) ERC; European Research Council (ERC) WT211276/Z/18/Z / Wellcome Human Cell Atlas Strategic Science Support; Wellcome Trust GN2779 / Action Medical Research CL-2017-01-004 / NIHR Clinical Lectureship RP-2017-08-ST2-002 / NIHR Research Professorship M944 / Rosetrees Trust 2017-174169 / Chan Zuckerberg Initiative; Chan Zuckerberg Initiative (CZI) Lister Institute for Preventive Medicine 21777 / Versus Arthritis Cure Challenge Research Grant UKRI Innovation/Rutherford Fund Fellowship by the MRC COVID_CSmith_017 / GOSH Children's charity C9545/A29580 / Cancer Research UK Barbour Foundation PhD studentship 107630/Z/15/Z / Wellcome/Royal Society; Wellcome Trust BB/P002293/1; BB/V006738/1 / BBSRC; UK Research & Innovation (UKRI); Biotechnology and Biological Sciences Research Council (BBSRC) Aging Biology Foundation 212516/Z/18/Z / Wellcome Trust UKRI/NIHR through the UK Coronavirus Immunology Consortium. Barbour Foundation EU MRG-Grammar awards WT211276/Z/18/Z; WT107931/Z/15/Z; 206328/Z/17/Z; WT206194; 207556_Z_17_Z; 211153/Z/18/Z; 203151/Z/16/Z / Wellcome; Wellcome Trust European Molecular Biology Laboratory BMA Foundation
Identifiers: 99820327402346
Academic Unit: Faculty of Health and Medical Sciences; FHMS Central Faculty Admin
Language: English
Resource Type: Journal article

Single-cell multi-omics analysis of the immune response in COVID-19

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