Journal
NATURE BIOTECHNOLOGY
Volume 40, Issue 3, Pages 319-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41587-021-01037-9
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Funding
- BIH COVID-19 research program
- fightCOVID@DKFZ initiative, the European commission (ESPACE) [874719]
- German Federal Ministry for Education and Research (BMBF) [de.NBI, 031A537B, 031A533A, 031A538A, 031A533B, 031A535A, 031A537C, 031A534A, 031A532B]
- BMBF [01ZZ1802A -01ZZ1802Z, 01IK20337, 82DZL0098B1]
- German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) [CRC-TR 84 B08, CRC-1449 Z01, ID 272983813-TRR179]
- DFG COVID-19 focus funding project [BI1693/2-1]
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Children exhibit higher basal expression of relevant pattern recognition receptors in airway immune cells, resulting in stronger early innate antiviral responses to SARS-CoV-2 infection compared to adults. Unique immune cell subpopulations, including cytotoxic T cells and memory CD8+ T cells, predominantly occur in children.
Single-cell sequencing reveals pre-activated immunity as important for milder COVID-19 symptoms in children. Children have reduced severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection rates and a substantially lower risk for developing severe coronavirus disease 2019 compared with adults. However, the molecular mechanisms underlying protection in younger age groups remain unknown. Here we characterize the single-cell transcriptional landscape in the upper airways of SARS-CoV-2-negative (n = 18) and age-matched SARS-CoV-2-positive (n = 24) children and corresponding samples from adults (n = 44), covering an age range of 4 weeks to 77 years. Children displayed higher basal expression of relevant pattern recognition receptors such as MDA5 (IFIH1) and RIG-I (DDX58) in upper airway epithelial cells, macrophages and dendritic cells, resulting in stronger innate antiviral responses upon SARS-CoV-2 infection than in adults. We further detected distinct immune cell subpopulations including KLRC1 (NKG2A)(+) cytotoxic T cells and a CD8(+) T cell population with a memory phenotype occurring predominantly in children. Our study provides evidence that the airway immune cells of children are primed for virus sensing, resulting in a stronger early innate antiviral response to SARS-CoV-2 infection than in adults.
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