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

Author

Listed:
  • Masahiro Yoshida

    (University College London
    Jikei University School of Medicine)

  • Kaylee B. Worlock

    (University College London)

  • Ni Huang

    (Wellcome Sanger Institute)

  • Rik G. H. Lindeboom

    (Wellcome Sanger Institute)

  • Colin R. Butler

    (NIHR Great Ormond Street BRC and UCL Institute of Child Health
    Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Natsuhiko Kumasaka

    (Wellcome Sanger Institute)

  • Cecilia Dominguez Conde

    (Wellcome Sanger Institute)

  • Lira Mamanova

    (Wellcome Sanger Institute)

  • Liam Bolt

    (Wellcome Sanger Institute)

  • Laura Richardson

    (Wellcome Sanger Institute)

  • Krzysztof Polanski

    (Wellcome Sanger Institute)

  • Elo Madissoon

    (Wellcome Sanger Institute
    European Molecular Biology Laboratory, European Bioinformatics Institute)

  • Josephine L. Barnes

    (University College London)

  • Jessica Allen-Hyttinen

    (University College London)

  • Eliz Kilich

    (University College London Hospitals NHS Foundation Trust)

  • Brendan C. Jones

    (NIHR Great Ormond Street BRC and UCL Institute of Child Health
    Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Angus Wilton

    (University College London Hospitals NHS Foundation Trust)

  • Anna Wilbrey-Clark

    (Wellcome Sanger Institute)

  • Waradon Sungnak

    (Wellcome Sanger Institute)

  • J. Patrick Pett

    (Wellcome Sanger Institute)

  • Juliane Weller

    (Wellcome Sanger Institute)

  • Elena Prigmore

    (Wellcome Sanger Institute)

  • Henry Yung

    (University College London
    University College London Hospitals NHS Foundation Trust)

  • Puja Mehta

    (University College London
    University College London Hospitals NHS Foundation Trust)

  • Aarash Saleh

    (Royal Free Hospital NHS Foundation Trust)

  • Anita Saigal

    (Royal Free Hospital NHS Foundation Trust)

  • Vivian Chu

    (Royal Free Hospital NHS Foundation Trust)

  • Jonathan M. Cohen

    (University College London Hospitals NHS Foundation Trust)

  • Clare Cane

    (Royal Free Hospital NHS Foundation Trust)

  • Aikaterini Iordanidou

    (Royal Free Hospital NHS Foundation Trust)

  • Soichi Shibuya

    (NIHR Great Ormond Street BRC and UCL Institute of Child Health)

  • Ann-Kathrin Reuschl

    (University College London)

  • Iván T. Herczeg

    (University College London)

  • A. Christine Argento

    (Northwestern University Feinberg School of Medicine)

  • Richard G. Wunderink

    (Northwestern University Feinberg School of Medicine)

  • Sean B. Smith

    (Northwestern University Feinberg School of Medicine)

  • Taylor A. Poor

    (Northwestern University Feinberg School of Medicine)

  • Catherine A. Gao

    (Northwestern University Feinberg School of Medicine)

  • Jane E. Dematte

    (Northwestern University Feinberg School of Medicine)

  • Gary Reynolds

    (Newcastle University)

  • Muzlifah Haniffa

    (Wellcome Sanger Institute
    Newcastle University)

  • Georgina S. Bowyer

    (University of Cambridge)

  • Matthew Coates

    (University of Cambridge
    Cambridge University Hospitals NHS Foundation Trust)

  • Menna R. Clatworthy

    (Wellcome Sanger Institute
    University of Cambridge)

  • Fernando J. Calero-Nieto

    (University of Cambridge)

  • Berthold Göttgens

    (University of Cambridge)

  • Christopher O’Callaghan

    (NIHR Great Ormond Street BRC and UCL Institute of Child Health
    Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Neil J. Sebire

    (NIHR Great Ormond Street BRC and UCL Institute of Child Health
    Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Clare Jolly

    (University College London)

  • Paolo De Coppi

    (NIHR Great Ormond Street BRC and UCL Institute of Child Health
    Great Ormond Street Hospital for Children NHS Foundation Trust)

  • Claire M. Smith

    (NIHR Great Ormond Street BRC and UCL Institute of Child Health)

  • Alexander V. Misharin

    (Northwestern University Feinberg School of Medicine)

  • Sam M. Janes

    (University College London
    University College London Hospitals NHS Foundation Trust)

  • Sarah A. Teichmann

    (Wellcome Sanger Institute
    University of Cambridge)

  • Marko Z. Nikolić

    (University College London
    University College London Hospitals NHS Foundation Trust)

  • Kerstin B. Meyer

    (Wellcome Sanger Institute)

Abstract

It is not fully understood why COVID-19 is typically milder in children1–3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after 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 characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.

Suggested Citation

  • Masahiro Yoshida & Kaylee B. Worlock & Ni Huang & Rik G. H. Lindeboom & Colin R. Butler & Natsuhiko Kumasaka & Cecilia Dominguez Conde & Lira Mamanova & Liam Bolt & Laura Richardson & Krzysztof Polans, 2022. "Local and systemic responses to SARS-CoV-2 infection in children and adults," Nature, Nature, vol. 602(7896), pages 321-327, February.
  • Handle: RePEc:nat:nature:v:602:y:2022:i:7896:d:10.1038_s41586-021-04345-x
    DOI: 10.1038/s41586-021-04345-x
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    Citations

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    Cited by:

    1. Scott R. Tyler & Daniel Lozano-Ojalvo & Ernesto Guccione & Eric E. Schadt, 2024. "Anti-correlated feature selection prevents false discovery of subpopulations in scRNAseq," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Quy Xiao Xuan Lin & Deepa Rajagopalan & Akshamal M. Gamage & Le Min Tan & Prasanna Nori Venkatesh & Wharton O. Y. Chan & Dilip Kumar & Ragini Agrawal & Yao Chen & Siew-Wai Fong & Amit Singh & Louisa J, 2024. "Longitudinal single cell atlas identifies complex temporal relationship between type I interferon response and COVID-19 severity," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    3. Alessia Raineri & Thomas Radtke & Sonja Rueegg & Sarah R. Haile & Dominik Menges & Tala Ballouz & Agne Ulyte & Jan Fehr & Daniel L. Cornejo & Giuseppe Pantaleo & Céline Pellaton & Craig Fenwick & Milo, 2023. "Persistent humoral immune response in youth throughout the COVID-19 pandemic: prospective school-based cohort study," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    4. Juanjie Tang & Tanya Novak & Julian Hecker & Gabrielle Grubbs & Fatema Tuz Zahra & Lorenza Bellusci & Sara Pourhashemi & Janet Chou & Kristin Moffitt & Natasha B. Halasa & Stephanie P. Schwartz & Trac, 2022. "Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Asmaa Hachim & Haogao Gu & Otared Kavian & Masashi Mori & Mike Y. W. Kwan & Wai Hung Chan & Yat Sun Yau & Susan S. Chiu & Owen T. Y. Tsang & David S. C. Hui & Chris K. P. Mok & Fionn N. L. Ma & Eric H, 2022. "SARS-CoV-2 accessory proteins reveal distinct serological signatures in children," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    6. Tabea M. Eser & Olga Baranov & Manuel Huth & Mohammed I. M. Ahmed & Flora Deák & Kathrin Held & Luming Lin & Kami Pekayvaz & Alexander Leunig & Leo Nicolai & Georgios Pollakis & Marcus Buggert & David, 2023. "Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    7. Alexander C. Dowell & Tara Lancaster & Rachel Bruton & Georgina Ireland & Christopher Bentley & Panagiota Sylla & Jianmin Zuo & Sam Scott & Azar Jadir & Jusnara Begum & Thomas Roberts & Christine Step, 2023. "Immunological imprinting of humoral immunity to SARS-CoV-2 in children," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    8. Andreas Fønss Møller & Jesper Grud Skat Madsen, 2023. "JOINTLY: interpretable joint clustering of single-cell transcriptomes," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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