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Clinical analysis and pluripotent stem cells-based model reveal possible impacts of ACE2 and lung progenitor cells on infants vulnerable to COVID-19.
Zhang, Zhao; Guo, Liyan; Lu, Xiaoxia; Zhang, Che; Huang, Li; Wang, Xianfeng; Duan, Fuyu; Liang, Huiying; Chen, Peikai; Zeng, Liang; Shao, Jianbo; Li, Hui; Li, Le; Liu, Li; Li, Cheng; Zhang, Jinqiu; Ma, Chui Yan; Kwan, Ka Yi; Liu, Wei; Xu, Yi; Gu, Xiaoqiong; Jiang, Hua; Du, Hui; Zhang, Ting; Wu, Yanheng; Yu, Guangyin; Chen, Junhui; Luo, Ruibang; Liao, Can; Tse, Hung-Fat; Chen, Zhiwei; Chen, Huanhuan Joyce; Xia, Huimin; Lian, Qizhou.
  • Zhang Z; Prenatal Diagnostic Center and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Guo L; Department of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Lu X; Prenatal Diagnostic Center and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Zhang C; Department of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Huang L; Department of Paediatrics, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, Hubei, China.
  • Wang X; Prenatal Diagnostic Center and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Duan F; Department of Paediatrics, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, Hubei, China.
  • Liang H; Department of Pediatric, Third People's Hospital of Shenzhen, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China.
  • Chen P; Prenatal Diagnostic Center and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Zeng L; The Pritzker school of Molecular Engineering, the Ben May department of Cancer Research, The University of Chicago, Chicago, USA.
  • Shao J; Guangdong Provincial Children's Medical Research Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Li H; School of Biomedical Sciences, the University of Hong Kong, Hong Kong SAR, China.
  • Li L; Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Liu L; Department of Pediatric, Third People's Hospital of Shenzhen, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, Guangdong, China.
  • Li C; Department of Haematology, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Zhang J; Department of Haematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Ma CY; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Kwan KY; Department of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Liu W; Prenatal Diagnostic Center and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Xu Y; Department of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Gu X; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Jiang H; Department of Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Du H; Department of Emergency Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Zhang T; Department of Clinical Biological Resource Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Wu Y; Department of Haematology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Yu G; Department of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Chen J; Department of Pathology, Fuyang People's Hospital, Anhui, China.
  • Luo R; Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, Australia.
  • Liao C; Department of Pathology, Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen, China.
  • Tse HF; Department of Pathology, Intervention and Cell Therapy Center, Peking University Shenzhen Hospital, Shenzhen, China.
  • Chen Z; Department of Computer Science, the University of Hong Kong, Hong Kong SAR, China.
  • Chen HJ; Prenatal Diagnostic Center and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Xia H; Department of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Lian Q; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
Theranostics ; 11(5): 2170-2181, 2021.
Article in English | MEDLINE | ID: covidwho-1016389
Semantic information from SemMedBD (by NLM)
1. Stem cells PART_OF Lung
Subject
Stem cells
Predicate
PART_OF
Object
Lung
2. Infant LOCATION_OF angiotensin converting enzyme 2
Subject
Infant
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
3. Child LOCATION_OF angiotensin converting enzyme 2
Subject
Child
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
4. COVID-19 PROCESS_OF Child
Subject
COVID-19
Predicate
PROCESS_OF
Object
Child
5. Lung LOCATION_OF Biopsy
Subject
Lung
Predicate
LOCATION_OF
Object
Biopsy
6. Biopsy ADMINISTERED_TO Child
Subject
Biopsy
Predicate
ADMINISTERED_TO
Object
Child
7. Pneumonia PROCESS_OF Infant
Subject
Pneumonia
Predicate
PROCESS_OF
Object
Infant
8. Lung LOCATION_OF angiotensin converting enzyme 2
Subject
Lung
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
9. angiotensin converting enzyme 2 INTERACTS_WITH Type-II Pneumocytes
Subject
angiotensin converting enzyme 2
Predicate
INTERACTS_WITH
Object
Type-II Pneumocytes
10. Pseudovirus PROCESS_OF Child
Subject
Pseudovirus
Predicate
PROCESS_OF
Object
Child
11. COVID-19 PROCESS_OF Infant
Subject
COVID-19
Predicate
PROCESS_OF
Object
Infant
12. Lung Development PROCESS_OF young child
Subject
Lung Development
Predicate
PROCESS_OF
Object
young child
13. Stem cells PART_OF Lung
Subject
Stem cells
Predicate
PART_OF
Object
Lung
14. Infant LOCATION_OF angiotensin converting enzyme 2
Subject
Infant
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
15. Child LOCATION_OF angiotensin converting enzyme 2
Subject
Child
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
16. COVID-19 PROCESS_OF Child
Subject
COVID-19
Predicate
PROCESS_OF
Object
Child
17. Lung LOCATION_OF Biopsy
Subject
Lung
Predicate
LOCATION_OF
Object
Biopsy
18. Biopsy ADMINISTERED_TO Child
Subject
Biopsy
Predicate
ADMINISTERED_TO
Object
Child
19. Pneumonia PROCESS_OF Infant
Subject
Pneumonia
Predicate
PROCESS_OF
Object
Infant
20. Lung LOCATION_OF angiotensin converting enzyme 2
Subject
Lung
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
21. angiotensin converting enzyme 2 INTERACTS_WITH Type-II Pneumocytes
Subject
angiotensin converting enzyme 2
Predicate
INTERACTS_WITH
Object
Type-II Pneumocytes
22. Pseudovirus PROCESS_OF Child
Subject
Pseudovirus
Predicate
PROCESS_OF
Object
Child
23. COVID-19 PROCESS_OF Infant
Subject
COVID-19
Predicate
PROCESS_OF
Object
Infant
24. Lung Development PROCESS_OF young child
Subject
Lung Development
Predicate
PROCESS_OF
Object
young child
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+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.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Stem Cells / Angiotensin-Converting Enzyme 2 / COVID-19 / Lung Type of study: Controlled clinical trial / Etiology study / Prognostic study / Risk factors Limits: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male / Infant, Newborn Language: English Journal: Theranostics Year: 2021 Document Type: Article Affiliation country: Thno.53136

Full text: Available Collection: International databases Database: MEDLINE Main subject: Stem Cells / Angiotensin-Converting Enzyme 2 / COVID-19 / Lung Type of study: Controlled clinical trial / Etiology study / Prognostic study / Risk factors Limits: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male / Infant, Newborn Language: English Journal: Theranostics Year: 2021 Document Type: Article Affiliation country: Thno.53136