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Pre-activated anti-viral innate immunity in the upper airways controls early SARS-CoV-2 infection in children

Children have reduced SARS-CoV-2 infection rates and a substantially lower risk for developing severe COVID-19 than 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 children (n=24) and corresponding samples from adults (n=44), covering an age range of four weeks to 77 years. Children displayed higher basal expression of the relevant pattern recognition receptors (PRR) 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 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 responses to SARS-CoV-2 infection than adults.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001007969 Illumina NovaSeq 6000 86
Publications Citations
ELF5 is a potential respiratory epithelial cell-specific risk gene for severe COVID-19.
Nat Commun 13: 2022 4484
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