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

Yoshida, Masahiro; Worlock, Kaylee B.; Huang, Ni; Lindeboom, Rik G. H.; Butler, Colin R.; Kumasaka, Natsuhiko; Conde, Cecilia Dominguez; Mamanova, Lira; Bolt, Liam; Richardson, Laura; Polanski, Krzysztof; Madissoon, Elo; Barnes, Josephine L.; Allen-Hyttinen, Jessica; Kilich, Eliz; Jones, Brendan C.; Wilton, Angus; Wilbrey-Clark, Anna; Sungnak, Waradon; Pett, J. Patrick; Weller, Juliane; Prigmore, Elena; Yung, Henry; Mehta, Puja; Saleh, Aarash; Saigal, Anita; Chu, Vivian; Cohen, Jonathan M.; Cane, Clare; Iordanidou, Aikaterini; Shibuya, Soichi; Reuschl, Ann-Kathrin; Herczeg, Iván T.; Argento, A. Christine; Wunderink, Richard G.; Smith, Sean B.; Poor, Taylor A.; Gao, Catherine A.; Dematte, Jane E.; Reynolds, Gary; Haniffa, Muzlifah; Bowyer, Georgina S.; Coates, Matthew; Clatworthy, Menna R.; Calero-Nieto, Fernando J.; Göttgens, Berthold; O’Callaghan, Christopher; Sebire, Neil J.; Jolly, Clare; De Coppi, Paolo; Smith, Claire M.; Misharin, Alexander V.; Janes, Sam M.; Teichmann, Sarah A.; Nikolić, Marko Z.; Meyer, Kerstin B.

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

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 Polanski, Elo Madissoon, Josephine L. Barnes, Jessica Allen-Hyttinen, Eliz Kilich, Brendan C. Jones, Angus Wilton, Anna Wilbrey-Clark, Waradon Sungnak, J. Patrick Pett, Juliane Weller, Elena Prigmore, Henry Yung, Puja Mehta, Aarash Saleh, Anita Saigal, Vivian Chu, Jonathan M. Cohen, Clare Cane, Aikaterini Iordanidou, Soichi Shibuya, Ann-Kathrin Reuschl, Iván T. Herczeg, A. Christine Argento, Richard G. Wunderink, Sean B. Smith, Taylor A. Poor, Catherine A. Gao, Jane E. Dematte, Gary Reynolds, Muzlifah Haniffa, Georgina S. Bowyer, Matthew Coates, Menna R. Clatworthy, Fernando J. Calero-Nieto, Berthold Göttgens, Christopher O’Callaghan, Neil J. Sebire, Clare Jolly, Paolo De Coppi, Claire M. Smith, Alexander V. Misharin, Sam M. Janes, Sarah A. Teichmann, Marko Z. Nikolić () and Kerstin B. Meyer ()
Additional contact information
Masahiro Yoshida: University College London
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
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
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
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
Puja Mehta: University College London
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
Georgina S. Bowyer: University of Cambridge
Matthew Coates: University of Cambridge
Menna R. Clatworthy: Wellcome Sanger Institute
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
Neil J. Sebire: NIHR Great Ormond Street BRC and UCL Institute of Child Health
Clare Jolly: University College London
Paolo De Coppi: NIHR Great Ormond Street BRC and UCL Institute of Child Health
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
Sarah A. Teichmann: Wellcome Sanger Institute
Marko Z. Nikolić: University College London
Kerstin B. Meyer: Wellcome Sanger Institute

Nature, 2022, vol. 602, issue 7896, 321-327

Abstract: 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.

Date: 2022
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DOI: 10.1038/s41586-021-04345-x

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