tetano
Editor, Senior Moderator
Theranostics
. 2021 Jan 1;11(5):2170-2181.
doi: 10.7150/thno.53136. eCollection 2021.
Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19
Zhao Zhang[SUP] 1 2 [/SUP], Liyan Guo[SUP] 1 [/SUP], Xiaoxia Lu[SUP] 3 [/SUP], Che Zhang[SUP] 4 [/SUP], Li Huang[SUP] 1 4 [/SUP], Xianfeng Wang[SUP] 5 [/SUP], Fuyu Duan[SUP] 1 6 [/SUP], Huiying Liang[SUP] 7 [/SUP], Peikai Chen[SUP] 8 [/SUP], Liang Zeng[SUP] 9 [/SUP], Jianbo Shao[SUP] 5 [/SUP], Hui Li[SUP] 10 [/SUP], Le Li[SUP] 11 [/SUP], Li Liu[SUP] 12 [/SUP], Cheng Li[SUP] 2 [/SUP], Jinqiu Zhang[SUP] 1 [/SUP], Chui Yan Ma[SUP] 2 [/SUP], Ka Yi Kwan[SUP] 12 [/SUP], Wei Liu[SUP] 13 [/SUP], Yi Xu[SUP] 14 [/SUP], Xiaoqiong Gu[SUP] 15 [/SUP], Hua Jiang[SUP] 11 [/SUP], Hui Du[SUP] 3 [/SUP], Ting Zhang[SUP] 16 [/SUP], Yanheng Wu[SUP] 17 [/SUP], Guangyin Yu[SUP] 18 [/SUP], Junhui Chen[SUP] 18 [/SUP], Ruibang Luo[SUP] 19 [/SUP], Can Liao[SUP] 1 [/SUP], Hung-Fat Tse[SUP] 2 [/SUP], Zhiwei Chen[SUP] 12 [/SUP], Huanhuan Joyce Chen[SUP] 6 [/SUP], Huimin Xia[SUP] 7 [/SUP], Qizhou Lian[SUP] 2 1 [/SUP]
Affiliations
Abstract
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[SUP]+[/SUP]SOX9[SUP]+[/SUP] 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.
Keywords: ACE2; COVID-19; SARS-CoV-2 virus; children; lung development; lung progenitor cells; pluripotent stem cells; single cell RNA sequencing; vulnerability.
. 2021 Jan 1;11(5):2170-2181.
doi: 10.7150/thno.53136. eCollection 2021.
Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19
Zhao Zhang[SUP] 1 2 [/SUP], Liyan Guo[SUP] 1 [/SUP], Xiaoxia Lu[SUP] 3 [/SUP], Che Zhang[SUP] 4 [/SUP], Li Huang[SUP] 1 4 [/SUP], Xianfeng Wang[SUP] 5 [/SUP], Fuyu Duan[SUP] 1 6 [/SUP], Huiying Liang[SUP] 7 [/SUP], Peikai Chen[SUP] 8 [/SUP], Liang Zeng[SUP] 9 [/SUP], Jianbo Shao[SUP] 5 [/SUP], Hui Li[SUP] 10 [/SUP], Le Li[SUP] 11 [/SUP], Li Liu[SUP] 12 [/SUP], Cheng Li[SUP] 2 [/SUP], Jinqiu Zhang[SUP] 1 [/SUP], Chui Yan Ma[SUP] 2 [/SUP], Ka Yi Kwan[SUP] 12 [/SUP], Wei Liu[SUP] 13 [/SUP], Yi Xu[SUP] 14 [/SUP], Xiaoqiong Gu[SUP] 15 [/SUP], Hua Jiang[SUP] 11 [/SUP], Hui Du[SUP] 3 [/SUP], Ting Zhang[SUP] 16 [/SUP], Yanheng Wu[SUP] 17 [/SUP], Guangyin Yu[SUP] 18 [/SUP], Junhui Chen[SUP] 18 [/SUP], Ruibang Luo[SUP] 19 [/SUP], Can Liao[SUP] 1 [/SUP], Hung-Fat Tse[SUP] 2 [/SUP], Zhiwei Chen[SUP] 12 [/SUP], Huanhuan Joyce Chen[SUP] 6 [/SUP], Huimin Xia[SUP] 7 [/SUP], Qizhou Lian[SUP] 2 1 [/SUP]
Affiliations
- PMID: 33500718
- PMCID: PMC7797681
- DOI: 10.7150/thno.53136
Abstract
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[SUP]+[/SUP]SOX9[SUP]+[/SUP] 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.
Keywords: ACE2; COVID-19; SARS-CoV-2 virus; children; lung development; lung progenitor cells; pluripotent stem cells; single cell RNA sequencing; vulnerability.