Local and systemic responses to SARS-CoV-2 infection in children and adults.
Authors
Huang, Ni
Butler, Colin R
Madissoon, Elo
Kilich, Eliz
de Wilton, Angus
Wilbrey-Clark, Anna
Yung, Henry
Mehta, Puja
Saleh, Aarash
Saigal, Anita
Iordanidou, Aikaterini
Reuschl, Ann-Kathrin
Argento, A Christine
Smith, Sean B
Poor, Taylor A
Dematte, Jane E
NU SCRIPT Study Investigators
Coates, Matthew
Clatworthy, Menna R
O'Callaghan, Christopher
Sebire, Neil J
Publication Date
2022-02Journal Title
Nature
ISSN
0028-0836
Publisher
Springer Science and Business Media LLC
Volume
602
Issue
7896
Pages
321-327
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Yoshida, M., Worlock, K. B., Huang, N., Lindeboom, R. G., Butler, C. R., Kumasaka, N., Dominguez Conde, C., et al. (2022). Local and systemic responses to SARS-CoV-2 infection in children and adults.. Nature, 602 (7896), 321-327. https://doi.org/10.1038/s41586-021-04345-x
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.
Keywords
Article, /631/250/254, /631/337/2019, /631/208/514/1949, /631/326/596/4130, /13/51, /38/91, article
Sponsorship
Wellcome Trust (211276/D/18/Z)
European Commission Horizon 2020 (H2020) Societal Challenges (874656)
Medical Research Council (MR/S036113/1)
Medical Research Council (MC_PC_17230)
MRC (MR/W014556/1)
Medical Research Council (MR/R015635/1)
Medical Research Council (MR/S035842/1)
Identifiers
s41586-021-04345-x, 4345
External DOI: https://doi.org/10.1038/s41586-021-04345-x
This record's URL: https://www.repository.cam.ac.uk/handle/1810/333808
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
Statistics
Total file downloads (since January 2020). For more information on metrics see the
IRUS guide.