Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high. Here we investigate differences in the cellular landscape and function of paediatric (<12 years), adult (30–50 years) and older adult (>70 years) ex vivo cultured nasal epithelial cells in response to infection with SARS-CoV-2. We show that cell tropism of SARS-CoV-2, and expression of ACE2 and TMPRSS2 in nasal epithelial cell subtypes, differ between age groups. While ciliated cells are viral replication centres across all age groups, a distinct goblet inflammatory subtype emerges in infected paediatric cultures and shows high expression of interferon-stimulated genes and incomplete viral replication. In contrast, older adult cultures infected with SARS-CoV-2 show a proportional increase in basaloid-like cells, which facilitate viral spread and are associated with altered epithelial repair pathways. We confirm age-specific induction of these cell types by integrating data from in vivo COVID-19 studies and validate that our in vitro model recapitulates early epithelial responses to SARS-CoV-2 infection.

感染 SARS-CoV-2 的儿童很少发展为呼吸衰竭。然而，85岁以上感染者的死亡风险仍然很高。在此，我们研究了离体培养的儿童（<12 岁）、成人（30-50 岁）和老年人（>70 岁）鼻上皮细胞在响应 SARS-CoV-2 感染时细胞结构和功能的差异。我们发现，SARS-CoV-2 的细胞趋向性以及鼻上皮细胞亚型中 ACE2 和 TMPRSS2 的表达在不同年龄组之间存在差异。虽然纤毛细胞是所有年龄段的病毒复制中心，但受感染的儿科培养物中出现了一种独特的杯状炎症亚型，并显示出干扰素刺激基因的高表达和不完整的病毒复制。相比之下，感染 SARS-CoV-2 的老年人培养物显示类基底细胞呈比例增加，这促进了病毒传播并与上皮修复途径的改变有关。我们通过整合体内 COVID-19 研究的数据来确认这些细胞类型的年龄特异性诱导，并验证我们的体外模型重现了对 SARS-CoV-2 感染的早期上皮反应。