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 de 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, NU SCRIPT Study Investigators, 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, Kerstin B. Meyer
Abstract
It is not fully understood why COVID-19 is typically milder in children1,2,3. 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.
Datasets
1. PBMC
Metadata
Ethnicity
BMI
annotation_broad
annotation_detailed
annotation_detailed_fullNames
Age_group
COVID_severity
COVID_status
Group
Smoker
sample_id
sequencing_library
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Metadata
sample_id
donor_id
Group
Ethnicity_inferred
Smoker
COVID_status
COVID_severity
Kit_version
dataset
batch
Cell_type_annotation_level3
Cell_type_annotation_level1
Cell_type_annotation_level2
assay_ontology_term_id
cell_type_ontology_term_id
development_stage_ontology_term_id
disease_ontology_term_id
self_reported_ethnicity_ontology_term_id
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tissue_ontology_term_id
suspension_type
tissue_type
cell_type
assay
disease
organism
sex
tissue
self_reported_ethnicity
development_stage
CV001_KM885460812616 cells CV001_KM916635310449 cells CV001_KM94652787074 cells CV001_KM88535956378 cells CV001_KM88536006232 cells CV001_KM94643086192 cells CV001_KM88545615718 cells CV001_KM88546095657 cells CV001_KM88535485450 cells CV001_KM88535965369 cells CV001_KM94653725367 cells CV001_KM88545095314 cells CV001_KM88535995115 cells CV001_KM88535474775 cells CV001_KM94652764741 cells CV001_KM94653744739 cells CV001_KM91664474644 cells CV001_KM88536954174 cells CV001_KM88545594019 cells CV001_KM94651813970 cells CV001_KM88545133944 cells CV001_KM94652773841 cells CV001_KM94643093701 cells CV001_KM94651793665 cells CV001_KM88535443645 cells CV001_KM94643103635 cells CV001_KM91663503317 cells CV001_KM91663553240 cells CV001_KM88545113187 cells CV001_KM92943943151 cells CV001_KM88535983149 cells CV001_KM88545582922 cells CV001_KM88544632739 cells CV001_KM92943912697 cells CV001_KM88545122651 cells CV001_KM94651802589 cells CV001_KM91665772571 cells CV001_KM88536942421 cells CV001_KM88536492240 cells CV001_KM88546102098 cells CV001_KM88535941958 cells CV001_KM92942981934 cells CV001_KM94643041934 cells CV001_KM94651821907 cells CV001_KM88535491872 cells CV001_KM88545081821 cells CV001_KM88544621816 cells CV001_KM94653761649 cells CV001_KM88544601640 cells CV001_KM88545621618 cells CV001_KM94653711595 cells CV001_KM94643051403 cells CV001_KM88535971283 cells CV001_KM88544641280 cells CV001_KM91663491274 cells CV001_KM88545631239 cells CV001_KM88544581181 cells CV001_KM88535461158 cells CV001_KM88535501103 cells CV001_KM94653771076 cells CV001_KM88536971050 cells CV001_KM91663511005 cells Goblet 2 BPIFA2+28042 cells Goblet 2 inflammatory13651 cells Secretory GALNT4+7084 cells B mem activated3257 cells B mem exhausted1668 cells Basal 1 KHDRBS2+870 cells Hillock precursor430 cells Goblet inflammatory13651 cells T CD8 IFN responsive383 cells HsapDv:000008659821 cells HsapDv:000008438869 cells HsapDv:000008330125 cells HsapDv:000008726383 cells HsapDv:000008219505 cells HsapDv:000008518787 cells HsapDv:000009317540 cells HsapDv:000016413020 cells MONDO:0100096104121 cells HANCESTRO:0005130524 cells HANCESTRO:000632307 cells HANCESTRO:001024690 cells HANCESTRO:000914306 cells NCBITaxon:9606236977 cells UBERON:0001707198868 cells UBERON:000312620987 cells UBERON:000218517122 cells tracheal goblet cell68741 cells basal cell of epithelium of trachea32681 cells secretory cell29713 cells CD8-positive, alpha-beta memory T cell4336 cells multi-ciliated epithelial cell2492 cells pulmonary ionocyte2289 cells duct epithelial cell1434 cells alternatively activated macrophage1270 cells CD4-positive, alpha-beta memory T cell1179 cells CD16-negative, CD56-bright natural killer cell, human889 cells squamous epithelial cell855 cells plasmacytoid dendritic cell, human498 cells CD16-positive, CD56-dim natural killer cell, human445 cells mucosal invariant T cell352 cells gamma-delta T cell317 cells conventional dendritic cell292 cells regulatory T cell286 cells mature NK T cell182 cells T follicular helper cell128 cells innate lymphoid cell112 cells CD4-positive, alpha-beta T cell81 cells neuroendocrine cell64 cells brush cell of trachea61 cells follicular dendritic cell49 cells adolescent stage59821 cells 2-5 year-old child stage38869 cells human adult stage26383 cells newborn human stage19505 cells 6-12 year-old child stage18787 cells human aged stage17540 cells 70-year-old human stage13020 cells 25-year-old human stage5314 cells 52-year-old human stage3944 cells 39-year-old human stage1618 cells 76-year-old human stage1239 cells 56-year-old human stage791 cells 73-year-old human stage21 cells Analyze this study
Source data
https://cellxgene.cziscience.com/collections/03f821b4-87be-4ff4-b65a-b5fc00061da7
Alias names
GSE168215, EGAD00001007718, PMID34937051 PMC8828466
Cite this study
Yoshida, M., Worlock, K.B., Huang, N., Lindeboom, R.G., Butler, C.R., Kumasaka, N., Dominguez Conde, C., Mamanova, L., Bolt, L., Richardson, L. and Polanski, K., 2022. Local and systemic responses to SARS-CoV-2 infection in children and adults. Nature, 602(7896), pp.321-327. https://doi.org/10.1038/s41586-021-04345-x
