Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19.
Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19.
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作者：
Zhang Z;Guo L;Lu X;Zhang C;Huang L;Wang X;Duan F;Liang H;Chen P;Zeng L;Shao J;Li H;Li L;Liu L;Li C;Zhang J;Ma CY;Kwan KY;Liu W;Xu Y;Gu X;Jiang H;Du H;Zhang T;Wu Y;Yu G;Chen J;Luo R;Liao C;Tse HF;Chen Z;Chen HJ;Xia H;Lian Q
简介：据报道，越来越多的儿童患有2019年严重冠状病毒病（COVID-19），但在不同发育阶段的儿童中，疾病严重程度和血管紧张素转换酶2（ACE 2）的表达模式在很大程度上尚不清楚。方法：我们分析了173名COVID-19儿童（0-15岁）的临床特征。旧）2020年1月22日至2020年3月15日。我们通过结合儿童肺活检、多能干细胞衍生的肺细胞、RNA测序谱和离体SARS-CoV-2假病毒感染，系统地研究了ACE 2在儿童不同发育阶段的表达和分布。结果：1岁以下婴幼儿（<1岁）年龄较大的儿童（> 1岁至老年人）对肺损伤的抵抗力更强。然而，ACE 2的表达水平在儿童肺中不随年龄而变化。ACE 2不仅在肺泡II型（AT II）细胞中显着表达，而且在多能干细胞衍生物和婴儿肺部检测到的SOX 9阳性肺祖细胞中也显着表达。ACE 2 + SOX 9+细胞容易被SARS-CoV-2假病毒感染，并且在年龄较大的儿童中双阳性细胞的数量显著减少。结论：婴儿（< 1岁-感染SARS-CoV-2的老年人更容易受到肺损伤。包括SOX 9阳性祖细胞在内的多种类型肺细胞中的ACE 2表达，与尚未建立的免疫系统协同作用，可能是导致COVID-19婴儿易感性的风险因素。有必要继续监测从SARS-CoV-2感染中康复的幼儿的肺部发育。
Introduction: An increasing number of children with severe coronavirus disease 2019 (COVID-19) is being reported, yet the spectrum of disease severity and expression patterns of angiotensin-converting enzyme 2 (ACE2) in children at different developmental stages are largely unknow. Methods: We analysed clinical features in a cohort of 173 children with COVID-19 (0-15 yrs.-old) between January 22, 2020 and March 15, 2020. We systematically examined the expression and distribution of ACE2 in different developmental stages of children by using a combination of children's lung biopsies, pluripotent stem cell-derived lung cells, RNA-sequencing profiles, and ex vivo SARS-CoV-2 pseudoviral infections. Results: It revealed that infants (< 1yrs.-old), with a weaker potency of immune response, are more vulnerable to develop pneumonia whereas older children (> 1 yrs.-old) are more resistant to lung injury. The expression levels of ACE2 however do not vary by age in children's lung. ACE2 is notably expressed not only in Alveolar Type II (AT II) cells, but also in SOX9 positive lung progenitor cells detected in both pluripotent stem cell derivatives and infants' lungs. The ACE2+SOX9+ cells are readily infected by SARS-CoV-2 pseudovirus and the numbers of the double positive cells are significantly decreased in older children. Conclusions: Infants (< 1 yrs.-old) with SARS-CoV-2 infection are more vulnerable to lung injuries. ACE2 expression in multiple types of lung cells including SOX9 positive progenitor cells, in cooperation with an unestablished immune system, could be risk factors contributing to vulnerability of infants with COVID-19. There is a need to continue monitoring lung development in young children who have recovered from SARS-CoV-2 infection.