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.

与成人相比，儿童的严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2) 感染率和 2019 年发生严重冠状病毒病的风险显着降低。然而，对年轻群体进行保护的分子机制仍然未知。在这里，我们描述了 SARS-CoV-2 阴性（n  = 18）和年龄匹配的 SARS-CoV-2 阳性（n  = 24）儿童和成人相应样本（n  = 44)，涵盖 4 周至 77 岁的年龄范围。儿童表现出更高的相关模式识别受体基础表达，例如 MDA5 ( IFIH1 ) 和 RIG-I ( DDX58) 在上呼吸道上皮细胞、巨噬细胞和树突状细胞中，导致对 SARS-CoV-2 感染的先天抗病毒反应比成人更强。我们进一步检测到不同的免疫细胞亚群，包括KLRC1 (NKG2A) ⁺细胞毒性 T 细胞和具有主要发生在儿童中的记忆表型的 CD8 ^{+ T 细胞群。}我们的研究提供的证据表明，儿童的气道免疫细胞已准备好进行病毒感应，导致对 SARS-CoV-2 感染的早期先天抗病毒反应比成人更强。