Browse by author
Lookup NU author(s): Dr Gary ReynoldsORCiD, Professor Muzlifah Haniffa
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.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.
Author(s): Yoshida M, Worlock KB, Huang N, Lindeboom RGH, Butler CR, Kumasaka N, Conde CD, Mamanova L, Bolt L, Richardson L, Polanski K, Madissoon E, Barnes JL, Allen-Hyttinen J, Kilich E, Jones BC, de Wilton A, Wilbrey-Clark A, Sungnak W, Pett JP, Weller J, Prigmore E, Yung H, Mehta P, Saleh A, Saigal A, Chu V, Cohen JM, Cane C, Iordanidou A, Shibuya S, Reuschl A-K, Herczeg IT, Argento AC, Wunderink RG, Smith SB, Gao CA, Dematte JE, Argento AC, Gao CA, Misharin AV, Budinger GRS, Dematte JE, Donnelly HK, Markov NS, Wunderink RG, Smith SB, Poor TA, Poor TA, Lu Z, Reynolds G, Haniffa M, Bowyer GS, Coates M, Clatworthy MR, Calero-Nieto FJ, Gottgens B, O'Callaghan C, Sebire NJ, Jolly C, de Coppi P, Smith CM, Misharin AV, Janes SM, Teichmann SA, Nikolic MZ, Meyer KB
Publication type: Article
Publication status: Published
Journal: Nature
Year: 2022
Volume: 602
Pages: 321-327
Print publication date: 10/02/2022
Online publication date: 22/12/2021
Acceptance date: 14/12/2021
Date deposited: 10/01/2024
ISSN (print): 0028-0836
ISSN (electronic): 1476-4687
Publisher: Nature Research
URL: https://doi.org/10.1038/s41586-021-04345-x
DOI: 10.1038/s41586-021-04345-x
Data Access Statement: The dataset from our study can be explored interactively through a web portal (https://covid19cellatlas.org). Quality control metrics for our single-cell data are provided at the web portal page. The data object, as a h5ad file, can also be downloaded from the portal page. The UK dataset is available at the European Genome–Phenome Archive under accession number EGAD00001007718. Counts matrices from bronchial brushings obtained from patients at Northwestern Memorial Hospital, Chicago, are available at the Gene Expression Omnibus under accession number GSE168215. As data are from living patients, these data are available under managed data access. Code availability All data analysis scripts are available at GitHub (https://github.com/Teichlab/COVID-19paed).
Altmetrics provided by Altmetric
