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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 321-327 |
| Number of pages | 7 |
| Journal | Nature |
| Volume | 602 |
| Issue number | 7896 |
| DOIs | |
| State | Published - Feb 10 2022 |
Funding
Acknowledgements We acknowledge assistance from L. Thorne, P. S. Chia, R. Hynds, J. Eliasova, D. King, M. Heightmann, M. Marks, M. Avari, T. Mistry, M. Shaw-Taylor, R. Pereira, J. Machta, J. Lim, R. Prendecki, C. Frauenfelder, J. Rudd, A. Hall and the staff at the Sanger Institute Core Sequencing facility. We thank R. Jenner and the staff at the UCLH/UCL Biomedical Research Centre for the use of their 10x Chromium controller. We acknowledge funding from Wellcome (WT211276/Z/18/Z and Sanger core grant WT206194). M.Z.N., S.M.J. and K.B.M. have been funded by the Rosetrees Trust (M944, M35-F2) and from Action Medical Research (GN2911). This project has been made possible in part by grants 2017-174169 and 2019-202654 from the Chan Zuckerberg Foundation and has received funding from the European Union’s Horizon 2020 Research and Innovation programme under grant agreement no. 874656. M.Z.N. acknowledges funding from the Rutherford Fund Fellowship allocated by the MRC, and M.Z.N. and S.M.J. from the UK Regenerative Medicine Platform 2 (MR/5005579/1), the Longfonds BREATH consortium and University College London Hospitals Biomedical Research Centre. M.Y. is funded by The Jikei University School of Medicine. K.B.W. acknowledges funding from University College London, Birkbeck MRC Doctoral Training Programme. C.M.S. and M.Z.N. acknowledge support from BBSRC (BB/V006738/1). We acknowledge support from the NIHR Great Ormond Street Biomedical Research Centre and the Great Ormond Street Hospital Children’s Charity. S.S. was supported by a Japan Society for the Promotion of Science Overseas Fellowship (310072). R.G.W. was supported by NIH grant U19AI135964 and a GlaxoSmithKline Distinguished Scholar in Respiratory Health grant from the CHEST Foundation. A.V.M. was supported by NIH grant U19AI135964. This publication is part of the Human Cell Atlas (www.humancellatlas.org/publications/).
ASJC Scopus subject areas
- General