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Local and systemic responses to SARS-CoV-2 infection in children and adults - Nature.com

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Abstract

It is not fully understood why COVID-19 is typically milder in children1–3. To examine differences in response to SARS-CoV-2 infection in children and adults, we analysed paediatric and adult COVID-19 patients and healthy controls (total n=93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In healthy paediatric airways, we observed cells already in an interferon-activated state, that upon SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon-responses restrict viral replication and disease progression. The systemic response in children was characterised by increases in naive lymphocytes and a depletion of natural killer cells, while in adults cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signaling in early infection, and identify novel epithelial cell states that associate with COVID-19 and age. Our matching nasal and blood data showed a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were massively reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.

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Author notes

  1. These authors contributed equally: Masahiro Yoshida, Kaylee B. Worlock, Ni Huang, Rik G.H. Lindeboom

  2. These authors jointly supervised this work: Marko Z. Nikolić, Kerstin B. Meyer

Affiliations

  1. UCL Respiratory, Division of Medicine, University College London, London, UK

    Masahiro Yoshida, Kaylee B. Worlock, Josephine L. Barnes, Jessica Allen-Hyttinen, Henry Yung, Puja Mehta, Iván T. Herczeg, Sam M. Janes & Marko Z. Nikolić

  2. Wellcome Sanger Institute, Cambridge, UK

    Ni Huang, Rik G. H. Lindeboom, Natsuhiko Kumasaka, Cecilia Dominguez Conde, Lira Mamanova, Liam Bolt, Laura Richardson, Krzysztof Polanski, Elo Madissoon, Anna Wilbrey-Clark, Waradon Sungnak, J. Patrick Pett, Juliane Weller, Elena Prigmore, Muzlifah Haniffa, Menna R. Clatworthy, Sarah A. Teichmann & Kerstin B. Meyer

  3. University College London Hospitals NHS Foundation Trust, London, UK

    Eliz Kilich, Angus de Wilton, Henry Yung, Puja Mehta, Jonathan M. Cohen, Sam M. Janes & Marko Z. Nikolić

  4. Royal Free Hospital NHS Foundation Trust, London, UK

    Aarash Saleh, Anita Saigal, Vivian Chu, Clare Cane & Aikaterini Iordanidou

  5. NIHR Great Ormond Street BRC and UCL Institute of Child Health, London, UK

    Colin R. Butler, Brendan C. Jones, Soichi Shibuya, Christopher O’Callaghan, Neil J. Sebire, Paolo de Coppi & Claire M. Smith

  6. UCL Division of Infection and Immunity, University College London, London, UK

    Ann-Kathrin Reuschl & Clare Jolly

  7. Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan

    Masahiro Yoshida

  8. Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, USA

    A. Christine Argento, Richard G. Wunderink, Sean B. Smith, Taylor A. Poor, Catherine A. Gao, Jane E. Dematte, A. Christine Argento, Catherine A. Gao, Alexander V. Misharin, G. R. Scott Budinger, Jane E. Dematte, Helen K. Donnelly, Nikolay S. Markov, Richard G. Wunderink, Sean B. Smith, Taylor A. Poor, Ziyan Lu & Alexander V. Misharin

  9. Wellcome - MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, UK

    Fernando J. Calero-Nieto & Berthold Göttgens

  10. European Molecular Biology Laboratory - European Bioinformatics Institute, Cambridge, UK

    Elo Madissoon

  11. Department of Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK

    Georgina S. Bowyer, Matthew Coates & Menna R. Clatworthy

  12. Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK

    Matthew Coates

  13. Biosciences Institute, Newcastle University, Newcastle upon Tyne, UK

    Gary Reynolds & Muzlifah Haniffa

  14. Dept Physics/Cavendish Laboratory, University of Cambridge, JJ Thomson Ave, Cambridge, CB3 0HE, UK

    Sarah A. Teichmann

Authors
  1. Masahiro Yoshida
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  2. Kaylee B. Worlock
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  3. Ni Huang
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  4. Rik G. H. Lindeboom
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  5. Colin R. Butler
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  6. Natsuhiko Kumasaka
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  7. Cecilia Dominguez Conde
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  8. Lira Mamanova
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  9. Liam Bolt
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  10. Laura Richardson
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  11. Krzysztof Polanski
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  12. Elo Madissoon
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  13. Josephine L. Barnes
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  14. Jessica Allen-Hyttinen
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  15. Eliz Kilich
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  16. Brendan C. Jones
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  17. Angus de Wilton
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  18. Anna Wilbrey-Clark
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  19. Waradon Sungnak
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  20. J. Patrick Pett
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  21. Juliane Weller
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  22. Elena Prigmore
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  23. Henry Yung
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  24. Puja Mehta
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  25. Aarash Saleh
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  26. Anita Saigal
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  27. Vivian Chu
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  28. Jonathan M. Cohen
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  29. Clare Cane
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  30. Aikaterini Iordanidou
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  31. Soichi Shibuya
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  32. Ann-Kathrin Reuschl
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  33. Iván T. Herczeg
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  34. A. Christine Argento
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  35. Richard G. Wunderink
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  36. Sean B. Smith
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  37. Taylor A. Poor
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  38. Catherine A. Gao
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  39. Jane E. Dematte
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  40. Gary Reynolds
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  41. Muzlifah Haniffa
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  42. Georgina S. Bowyer
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  43. Matthew Coates
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  44. Menna R. Clatworthy
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  45. Fernando J. Calero-Nieto
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  46. Berthold Göttgens
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  47. Christopher O’Callaghan
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  48. Neil J. Sebire
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  49. Clare Jolly
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  50. Paolo de Coppi
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  51. Claire M. Smith
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  52. Alexander V. Misharin
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  53. Sam M. Janes
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  54. Sarah A. Teichmann
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  55. Marko Z. Nikolić
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  56. Kerstin B. Meyer
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Consortia

NU SCRIPT Study Investigators

  • A. Christine Argento
  • , Catherine A. Gao
  • , Alexander V. Misharin
  • , G. R. Scott Budinger
  • , Jane E. Dematte
  • , Helen K. Donnelly
  • , Nikolay S. Markov
  • , Richard G. Wunderink
  • , Sean B. Smith
  • , Taylor A. Poor
  •  & Ziyan Lu

Corresponding authors

Correspondence to Marko Z. Nikolić or Kerstin B. Meyer.

Supplementary information

Supplementary Information

This Supplementary information file contains the following sections: Detailed Cell Type Annotation; Cell type abbreviations for airway and blood immune cells; IFN production in dendritic cells; and additional references.

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Yoshida, M., Worlock, K.B., Huang, N. et al. Local and systemic responses to SARS-CoV-2 infection in children and adults. Nature (2021). https://ift.tt/3H23jQf

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Local and systemic responses to SARS-CoV-2 infection in children and adults - Nature.com
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