Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19

Zhang, Zhao1,8; Guo, Liyan1; Lu, Xiaoxia13; Zhang, Che15; Huang, Li1,15; Wang, Xianfeng17; Duan, Fuyu1,16; Liang, Huiying2; Chen, Peikai11; Zeng, Liang3; Shao, Jianbo17; Li, Hui14; Li, Le6; Liu, Li9,10; Li, Cheng8; Zhang, Jinqiu1; Yan, Chui8; Kwan, Ka Yi9,10; Liu, Wei5; Xu, Yi7; Gu, Xiaoqiong4; Jiang, Hua6; Du, Hui13; Zhang, Ting18; Wu, Yanheng19; Yu, Guangyin20; Chen, Junhui20; Luo, Ruibang12; Liao, Can1; Tse, Hung-fat8; Chen, Zhiwei9,10; Chen, Huanhuan Joyce16; Xia, Huimin2; Lian, Qizhou1,8

2021

10.7150/thno.53136

Theranostics   影响因子和分区

1838-7640

["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."]

COVID-19 SARS-CoV-2 virus children lung development vulnerability ACE2 lung progenitor cells single cell RNA sequencing pluripotent stem cells

SCI

英语

其他

National Natural Science Grant of China[31571407,31970910] ; Hong Kong Health and Medical Research Fund (HMRF)[06172956] ; U.S. National Institute of Health[NCI R00 CA226353-01A1] ; Stem Cell and Regenerative Medicine Fund (Guangzhou Women and Children's Medical Center)[5001-4001010]

Research & Experimental Medicine

Medicine, Research & Experimental

WOS:000600556000013

IVYSPRING INT PUBL

Web of Science

1.Guangzhou Med Univ, Prenatal Diagnost Ctr & Cord Blood Bank, Guangzhou Women & Childrens Med Ctr, Guangzhou, Peoples R China
2.Guangzhou Med Univ, Guangdong Prov Childrens Med Res Ctr, Guangzhou Women & Childrens Med Ctr, Guangzhou, Peoples R China
3.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Pathol, Guangzhou, Peoples R China
4.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Clin Biol Resource Bank, Guangzhou, Peoples R China
5.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Surg, Guangzhou, Peoples R China
6.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Haematol, Guangzhou, Peoples R China
7.Guangzhou Med Univ, Guangzhou Women & Childrens Med Ctr, Dept Emergency Med, Guangzhou, Peoples R China
8.Univ Hong Kong, Dept Med, Hong Kong, Peoples R China
9.Univ Hong Kong, Li Ka Shing Fac Med, Aids Inst, Hong Kong, Peoples R China
10.Univ Hong Kong, Li Ka Shing Fac Med, Dept Microbiol, Hong Kong, Peoples R China
11.Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China
12.Univ Hong Kong, Dept Comp Sci, Hong Kong, Peoples R China
13.Huazhong Univ Sci & Technol, Wuhan Childrens Hosp, Tongji Med Coll, Dept Resp Med, Wuhan, Hubei, Peoples R China
14.Huazhong Univ Sci & Technol, Wuhan Childrens Hosp, Tongji Med Coll, Dept Haematol, Wuhan, Hubei, Peoples R China
15.Hubei Univ Med, Dept Paediat, Affiliated Taihe Hosp, Shiyan, Hubei, Peoples R China
16.Univ Chicago, Pritzker Sch Mol Engn, Ben May Dept Canc Res, Chicago, IL USA
17.Southern Univ Sci & Technol, Dept Pediat, Affiliated Hosp 2, Peoples Hosp Shenzhen 3, Shenzhen, Guangdong, Peoples R China
18.Fuyang Peoples Hosp, Dept Pathol, Fuyang, Anhui, Peoples R China
19.Univ Queensland, Australian Inst Bioengn & Nanotechnol AIBN, Brisbane, Qld, Australia
20.Peking Univ, Intervent & Cell Therapy Ctr, Dept Pathol, Shenzhen Hosp, Shenzhen, Peoples R China

Zhang, Zhao,Guo, Liyan,Lu, Xiaoxia,et al. Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19[J]. Theranostics,2021,11(5).

Zhang, Zhao.,Guo, Liyan.,Lu, Xiaoxia.,Zhang, Che.,Huang, Li.,...&Lian, Qizhou.(2021).Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19.Theranostics,11(5).

Zhang, Zhao,et al."Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19".Theranostics 11.5(2021).