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The cellular immune response to COVID-19 deciphered by single cell multi-omics across three UK centres
Emily Stephenson; Gary Reynolds; Rachel A Botting; Fernando J Calero-Nieto; Michael Morgan; Zewen Kelvin Tuong; Karsten Bach; Waradon Sungnak; Kaylee B Worlock; Masahiro Yoshida; Natsuhiko Kumasaka; Katarzyna Kania; Justin Engelbert; Bayanne Olabi; Jarmila Stremenova Spegarova; Nicola K Wilson; Nicole Mende; Laura Jardine; Louis CS Gardner; Issac Goh; Dave Horsfall; Jim McGrath; Simone Webb; Michael W Mather; Rik GH Lindeboom; Emma Dann; Ni Huang; Krzysztof Polanski; Elena Prigmore; Florian Gothe; Jonathan Scott; Rebecca P Payne; Kenneth F Baker; Aidan T Hanrath; Ina CD 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 Y 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 JA Duncan; Ken Smith; Sarah A Teichmann; Menna R Clatworthy; John C Marioni; Berthold Gottgens; Muzlifah Haniffa.
Afiliación
  • Emily Stephenson; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Gary Reynolds; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Rachel A Botting; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Fernando J Calero-Nieto; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
  • Michael Morgan; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK
  • Zewen Kelvin Tuong; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
  • Karsten Bach; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK
  • Waradon Sungnak; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Kaylee B Worlock; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Masahiro Yoshida; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Natsuhiko Kumasaka; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Katarzyna Kania; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
  • Justin Engelbert; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Bayanne Olabi; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Jarmila Stremenova Spegarova; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Nicola K Wilson; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
  • Nicole Mende; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
  • Laura Jardine; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Louis CS Gardner; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Issac Goh; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Dave Horsfall; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Jim McGrath; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Simone Webb; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Michael W Mather; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Rik GH Lindeboom; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Emma Dann; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Ni Huang; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Krzysztof Polanski; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Elena Prigmore; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Florian Gothe; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Jonathan Scott; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Rebecca P Payne; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Kenneth F Baker; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Aidan T Hanrath; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Ina CD Schim van der Loeff; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Andrew S Barr; Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation, UK
  • Amada Sanchez-Gonzalez; Department of Infection and Tropical Medicine, Newcastle upon Tyne Hospitals NHS Foundation, UK
  • Laura Bergamaschi; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, UK
  • Federica Mescia; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, UK
  • Josephine L Barnes; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Eliz Kilich; University College London Hospitals NHS Foundation Trust, London, UK
  • Angus de Wilton; University College London Hospitals NHS Foundation Trust, London, UK
  • Anita Saigal; Royal Free Hospital NHS Foundation Trust, London, UK
  • Aarash Saleh; Royal Free Hospital NHS Foundation Trust, London, UK
  • Sam M Janes; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Claire M Smith; UCL Great Ormond Street Institute of Child Health, London, UK
  • Nusayhah Gopee; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Caroline Wilson; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Paul Coupland; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
  • Jonathan M Coxhead; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
  • Vladimir Y Kiselev; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Stijn van Dongen; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Jaume Bacardit; School of Computing, Newcastle University, Newcastle Upon Tyne, UK
  • Hamish W King; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Anthony J Rostron; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • A John Simpson; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Sophie Hambleton; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Elisa Laurenti; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
  • Paul A Lyons; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, UK
  • Kerstin B Meyer; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Marko Z Nikolic; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Christopher JA Duncan; Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
  • Ken Smith; Cambridge Institute for Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, Cambridge Biomedical Campus, UK
  • Sarah A Teichmann; Wellcome Sanger Institute, Wellcome Genome Campus, Cambridge, UK
  • Menna R Clatworthy; Molecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK
  • John C Marioni; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Cambridge, UK
  • Berthold Gottgens; Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK
  • Muzlifah Haniffa; Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-21249725
ABSTRACT
The COVID-19 pandemic, caused by SARS coronavirus 2 (SARS-CoV-2), has resulted in excess morbidity and mortality as well as economic decline. To characterise the systemic host immune response to SARS-CoV-2, we performed single-cell RNA-sequencing coupled with analysis of cell surface proteins, providing molecular profiling of over 800,000 peripheral blood mononuclear cells from a cohort of 130 patients with COVID-19. Our cohort, from three UK centres, spans the spectrum of clinical presentations and disease severities ranging from asymptomatic to critical. Three control groups were included healthy volunteers, patients suffering from a non-COVID-19 severe respiratory illness and healthy individuals administered with intravenous lipopolysaccharide to model an acute inflammatory response. Full single cell transcriptomes coupled with quantification of 188 cell surface proteins, and T and B lymphocyte antigen receptor repertoires have provided several insights into COVID-19 1. a new non-classical monocyte state that sequesters platelets and replenishes the alveolar macrophage pool; 2. platelet activation accompanied by early priming towards megakaryopoiesis in immature haematopoietic stem/progenitor cells and expansion of megakaryocyte-primed progenitors; 3. increased clonally expanded CD8+ effectoreffector memory T cells, and proliferating CD4+ and CD8+ T cells in patients with more severe disease; and 4. relative increase of IgA plasmablasts in asymptomatic stages that switches to expansion of IgG plasmablasts and plasma cells, accompanied with higher incidence of BCR sharing, as disease severity increases. All data and analysis results are available for interrogation and data mining through an intuitive web portal. Together, these data detail the cellular processes present in peripheral blood during an acute immune response to COVID-19, and serve as a template for multi-omic single cell data integration across multiple centers to rapidly build powerful resources to help combat diseases such as COVID-19.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Cohort_studies / Experimental_studies / Observational_studies / Prognostic_studies / Rct / Review Idioma: En Año: 2021 Tipo del documento: Preprint
Texto completo
Añadir a Mi BVS
Imprimir
XML
Buscar en Google
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Cohort_studies / Experimental_studies / Observational_studies / Prognostic_studies / Rct / Review Idioma: En Año: 2021 Tipo del documento: Preprint