| Literature DB >> 34937051 |
Masahiro Yoshida1,2, Kaylee B Worlock1, Ni Huang3, Rik G H Lindeboom3, Colin R Butler4,5, Natsuhiko Kumasaka3, Cecilia Dominguez Conde3, Lira Mamanova3, Liam Bolt3, Laura Richardson3, Krzysztof Polanski3, Elo Madissoon3,6, Josephine L Barnes1, Jessica Allen-Hyttinen1, Eliz Kilich7, Brendan C Jones4,5, Angus de Wilton7, Anna Wilbrey-Clark3, Waradon Sungnak3, J Patrick Pett3, Juliane Weller3, Elena Prigmore3, Henry Yung1,7, Puja Mehta1,7, Aarash Saleh8, Anita Saigal8, Vivian Chu8, Jonathan M Cohen7, Clare Cane8, Aikaterini Iordanidou8, Soichi Shibuya4, Ann-Kathrin Reuschl9, Iván T Herczeg1, A Christine Argento10, Richard G Wunderink10, Sean B Smith10, Taylor A Poor10, Catherine A Gao10, Jane E Dematte10, Gary Reynolds11, Muzlifah Haniffa3,11, Georgina S Bowyer12, Matthew Coates12,13, Menna R Clatworthy3,12, Fernando J Calero-Nieto14, Berthold Göttgens14, Christopher O'Callaghan4,5, Neil J Sebire4,5, Clare Jolly9, Paolo De Coppi4,5, Claire M Smith4, Alexander V Misharin10, Sam M Janes1,7, Sarah A Teichmann3,15, Marko Z Nikolić16,17, Kerstin B Meyer18.
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.Entities:
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Year: 2021 PMID： 34937051 PMCID： PMC8828466 DOI： 10.1038/s41586-021-04345-x
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 69.504