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The local and systemic response to SARS-CoV-2 infection in children and adults
Masahiro Yoshida; Kaylee B Worlock; Ni Huang; Rik GH Lindeboom; Colin R Butler; Natsuhiko Kumasaka; Cecilia Dominguez Conde; Lira Mamanova; Liam Bolt; Laura Richardson; Krzysztof Polanski; Elo Madissoon; Josephine L Barnes; Jessica Allen-Hyttinen; Eliz Kilich; Brendan C Jones; Angus de Wilton; Anna Wilbrey-Clark; Waradon Sungnak; Jan Patrick Prett; Elena Prigmore; Henry Yung; Puja Mehta; Aarash Saleh; Anita Saigal; Vivian Chu; Jonathan M Cohen; Clare Cane; Aikaterini Iordanidou; Soichi Shibuya; Ann-Kathrin Reuschl; A. Christine Argento; Richard G Wunderink; Sean B Smith; Taylor A Poor; Catherine A Gao; Jane E Dematte; - NU SCRIPT Study Investigators; Gary Reynolds; Muzlifah Haniffa; Georgina S Bowyer; Matthew Coates; Menna R Clatworthy; Fernando J Calero-Nieto; Berthold Gottgens; Neil J Sebire; Clare Jolly; Paolo de Coppi; Claire M Smith; Alexander V Misharin; Sam M Janes; Sarah A Teichmann; Marko Z Nikolic; Kerstin B Meyer.
Afiliación
  • Masahiro Yoshida; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Kaylee B Worlock; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Ni Huang; Wellcome Sanger Institute, Cambridge, UK
  • Rik GH Lindeboom; Wellcome Sanger Institute, Cambridge, UK
  • Colin R Butler; UCL Great Ormond Street Institute of Child Health, London, UK
  • Natsuhiko Kumasaka; Wellcome Trust Sanger Institute
  • Cecilia Dominguez Conde; Wellcome Sanger Institute, Cambridge, UK
  • Lira Mamanova; Wellcome Sanger Institute, Cambridge, UK
  • Liam Bolt; Wellcome Sanger Institute, Cambridge, UK
  • Laura Richardson; Wellcome Sanger Institute, Cambridge, UK
  • Krzysztof Polanski; Wellcome Sanger Institute, Cambridge, UK
  • Elo Madissoon; Wellcome Sanger Institute, Cambridge, UK
  • Josephine L Barnes; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Jessica Allen-Hyttinen; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Eliz Kilich; University College London Hospitals NHS Foundation Trust, London, UK
  • Brendan C Jones; UCL Great Ormond Street Institute of Child Health, London, UK
  • Angus de Wilton; University College London Hospital Trust
  • Anna Wilbrey-Clark; Wellcome Sanger Institute, Cambridge, UK
  • Waradon Sungnak; Wellcome Sanger Institute
  • Jan Patrick Prett; Wellcome Sanger Institute, Cambridge, UK
  • Elena Prigmore; Wellcome Sanger Institute, Cambridge, UK
  • Henry Yung; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Puja Mehta; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Aarash Saleh; Royal Free Hospital, London, UK
  • Anita Saigal; Royal Free Hospital, London, UK
  • Vivian Chu; Royal Free Hospital, London, UK
  • Jonathan M Cohen; University College London Hospitals NHS Foundation Trust, London, UK
  • Clare Cane; Royal Free Hospital, London, UK
  • Aikaterini Iordanidou; Royal Free Hospital, London, UK
  • Soichi Shibuya; UCL Great Ormond Street Institute of Child Health, London, UK
  • Ann-Kathrin Reuschl; Division of Infection and Immunity, University College London, London, UK
  • A. Christine Argento; Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, USA
  • Richard G Wunderink; Northwestern University Feinberg School of Medicine
  • Sean B Smith; Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, USA
  • Taylor A Poor; Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, USA
  • Catherine A Gao; Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, USA
  • Jane E Dematte; Division of Pulmonary and Critical Care Medicine, Northwestern University, Feinberg School of Medicine, Chicago, USA
  • - NU SCRIPT Study Investigators;
  • Gary Reynolds; Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
  • Muzlifah Haniffa; Biosciences Institute, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK
  • Georgina S Bowyer; Department of Medicine, University of Cambridge, Cambridge CB2 0QQ, UK
  • Matthew Coates; University of Cambridge, Department of Medicine
  • Menna R Clatworthy; University of Cambride, Department of Medicine
  • Fernando J Calero-Nieto; Wellcome Trust & MRC Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge UK
  • Berthold Gottgens; Wellcome Trust & MRC Cambridge Stem Cell Institute and Department of Haematology, University of Cambridge, Cambridge UK
  • Neil J Sebire; NIHR Great Ormond Street BRC and Institute of Child Health, London, UK
  • Clare Jolly; Division of Infection and Immunity, University College London, UK
  • Paolo de Coppi; UCL Great Ormond Street Institute of Child Health, London, UK
  • Claire M Smith; UCL Great Ormond Street Institute of Child Health, London, UK
  • Alexander V Misharin; Northwestern University
  • Sam M Janes; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Sarah A Teichmann; Wellcome Sanger Institute, Cambridge, UK
  • Marko Z Nikolic; UCL Respiratory, Division of Medicine, University College London, London, UK
  • Kerstin B Meyer; Wellcome Sanger Institute, Cambridge, UK
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-21253012
ABSTRACT
While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples upper and lower airways and blood. We found striking differences children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in paediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatric versus adult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data1 as a highly granular reference for the study of immune responses in airways and blood in children.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV 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 Idioma: En Año: 2021 Tipo del documento: Preprint