Department of Pediatrics.
Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, and.
J Clin Invest. 2021 Jan 4;131(1). doi: 10.1172/JCI140766.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) novel coronavirus 2019 (COVID-19) global pandemic has led to millions of cases and hundreds of thousands of deaths. While older adults appear at high risk for severe disease, hospitalizations and deaths due to SARS-CoV-2 among children have been relatively rare. Integrating single-cell RNA sequencing (scRNA-seq) of developing mouse lung with temporally resolved immunofluorescence in mouse and human lung tissue, we found that expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1), and TMPRSS2 expression increased with aging in mice and humans. Analysis of autopsy tissue from fatal COVID-19 cases detected SARS-CoV-2 RNA most frequently in ciliated and secretory cells in airway epithelium and AT1 cells in peripheral lung. SARS-CoV-2 RNA was highly colocalized in cells expressing TMPRSS2. Together, these data demonstrate the cellular spectrum infected by SARS-CoV-2 in lung epithelium and suggest that developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）新型冠状病毒 2019（COVID-19）全球大流行导致了数百万人患病和数十万人死亡。虽然老年人患严重疾病、住院和因 SARS-CoV-2 而死亡的风险较高，但儿童因 SARS-CoV-2 住院和死亡的情况相对较少。我们通过对发育中的小鼠肺部进行单细胞 RNA 测序（scRNA-seq），并结合小鼠和人肺部组织中具有时间分辨能力的免疫荧光，发现 SARS-CoV-2 Spike 蛋白前体 TMPRSS2 在纤毛细胞和 I 型肺泡上皮细胞（AT1）中的表达最高，并且 TMPRSS2 的表达在小鼠和人类中随年龄增长而增加。对死于 COVID-19 的病例的尸检组织进行分析，在气道上皮细胞的纤毛细胞和分泌细胞以及外周肺的 AT1 细胞中最常检测到 SARS-CoV-2 RNA。SARS-CoV-2 RNA 与表达 TMPRSS2 的细胞高度共定位。这些数据共同表明了 SARS-CoV-2 在肺上皮细胞中感染的细胞谱，并表明 TMPRSS2 的发育调控可能是婴儿和儿童免受严重呼吸道疾病的相对保护的基础。
