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.
- Loske, J.
- Röhmel, J.
- Lukassen, S.
- Stricker, S.
- Magalhães, V. G.
- Liebig, J.
- Chua, R. L.
- Thürmann, L.
- Messingschlager, M.
- Seegebarth, A.
- Timmermann, B.
- Klages, S.
- Ralser, M.
- Sawitzki, B.
- Sander, L. E.
- Corman, V. M.
- Conrad, C.
- Laudi, S.
- Binder, M.
- Trump, S.
- Eils, R.
- Mall, M. A.
- Lehmann, I.
