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Distinct Disease Severity Between Children and Older Adults With Coronavirus Disease 2019 (COVID-19): Impacts of ACE2 Expression, Distribution, and Lung Progenitor Cells.
Zhang, Zhao; Guo, Liyan; Huang, Li; Zhang, Che; Luo, Ruibang; Zeng, Liang; Liang, Huiying; Li, Qiuhui; Lu, Xiaoxia; Wang, Xianfeng; Ma, Chui Yan; Shao, Jianbo; Luo, Weiren; Li, Le; Liu, Li; Li, Ziyue; Zhou, Xiaoya; Zhang, Xiaoxian; Liu, Jie; Yang, Jinjuan; Kwan, Ka Yi; Liu, Wei; Xu, Yi; Jiang, Hua; Liu, Hongsheng; Du, Hui; Wu, Yanheng; Yu, Guangyin; Chen, Junhui; Wu, Jieying; Zhang, Jinqiu; Liao, Can; Chen, Huanhuan Joyce; Chen, Zhiwei; Tse, Hung-Fat; Xia, Huimin; Lian, Qizhou.
  • Zhang Z; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Guo L; CardiologyDivision,Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Huang L; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Zhang C; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Luo R; Institute of Drug Clinical Trial, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, Hubei, China.
  • Zeng L; Department of Pediatrics, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, Hubei, China.
  • Liang H; Department of Computer Science, the University of Hong Kong, Hong Kong SAR, China.
  • Li Q; Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Lu X; Guangdong Provincial Children's Medical Research Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Wang X; Department of Computer Science, the University of Hong Kong, Hong Kong SAR, China.
  • Ma CY; Department of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
  • Shao J; Department of Pediatrics, Third People's Hospital of Shenzhen, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
  • Luo W; CardiologyDivision,Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Li L; Department of Pediatrics, Third People's Hospital of Shenzhen, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
  • Liu L; Department of Pathology, Third People's Hospital of Shenzhen, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China.
  • Li Z; Department of Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Zhou X; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Zhang X; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Liu J; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Yang J; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Kwan KY; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Liu W; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Xu Y; 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.
  • Liu H; Department of Emergency Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Du H; Department of Hematology & Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Wu Y; Department of Radiology, 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; Australian Institute for Bioengineering and Nanotechnology (AIBN), the University of Queensland, Brisbane, Australia.
  • Wu J; Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, China.
  • Zhang J; Intervention and Cell Therapy Centre, Peking University Shenzhen Hospital, Shenzhen, China.
  • Liao C; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Chen HJ; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Chen Z; Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
  • Tse HF; The Pritzker school of Molecular Engineering, the Ben May department of Cancer Research, the University of Chicago, Chicago, Illinois, USA.
  • Xia H; AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
  • Lian Q; CardiologyDivision,Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China.
Clin Infect Dis ; 73(11): e4154-e4165, 2021 12 06.
Article in English | MEDLINE | ID: covidwho-1559099
Semantic information from SemMedBD (by NLM)
1. Stem cells PART_OF Lung
Subject
Stem cells
Predicate
PART_OF
Object
Lung
2. Stem cells INTERACTS_WITH angiotensin converting enzyme 2
Subject
Stem cells
Predicate
INTERACTS_WITH
Object
angiotensin converting enzyme 2
3. COVID-19 PROCESS_OF Elderly (population group)
Subject
COVID-19
Predicate
PROCESS_OF
Object
Elderly (population group)
4. COVID-19 PROCESS_OF Child
Subject
COVID-19
Predicate
PROCESS_OF
Object
Child
5. 2019 novel coronavirus PROCESS_OF Child
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2019 novel coronavirus
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PROCESS_OF
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Child
6. 2019 novel coronavirus PROCESS_OF Patients
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2019 novel coronavirus
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PROCESS_OF
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Patients
7. COVID-19 PROCESS_OF Patients
Subject
COVID-19
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PROCESS_OF
Object
Patients
8. Lung LOCATION_OF Biopsy
Subject
Lung
Predicate
LOCATION_OF
Object
Biopsy
9. Elderly (population group) LOCATION_OF angiotensin converting enzyme 2
Subject
Elderly (population group)
Predicate
LOCATION_OF
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angiotensin converting enzyme 2
10. Child LOCATION_OF angiotensin converting enzyme 2
Subject
Child
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
11. Pseudovirus LOCATION_OF angiotensin converting enzyme 2
Subject
Pseudovirus
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
12. Lymphopenia PROCESS_OF Patients
Subject
Lymphopenia
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PROCESS_OF
Object
Patients
13. Pneumonia PROCESS_OF Patients
Subject
Pneumonia
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PROCESS_OF
Object
Patients
14. Inflammatory Response PROCESS_OF Patients
Subject
Inflammatory Response
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PROCESS_OF
Object
Patients
15. Patients LOCATION_OF angiotensin converting enzyme 2
Subject
Patients
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LOCATION_OF
Object
angiotensin converting enzyme 2
16. Tract PART_OF Lung
Subject
Tract
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PART_OF
Object
Lung
17. COVID-19 CAUSES Pneumonia
Subject
COVID-19
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CAUSES
Object
Pneumonia
18. Stem cells PART_OF Lung
Subject
Stem cells
Predicate
PART_OF
Object
Lung
19. Stem cells INTERACTS_WITH angiotensin converting enzyme 2
Subject
Stem cells
Predicate
INTERACTS_WITH
Object
angiotensin converting enzyme 2
20. COVID-19 PROCESS_OF Elderly (population group)
Subject
COVID-19
Predicate
PROCESS_OF
Object
Elderly (population group)
21. COVID-19 PROCESS_OF Child
Subject
COVID-19
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PROCESS_OF
Object
Child
22. 2019 novel coronavirus PROCESS_OF Child
Subject
2019 novel coronavirus
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PROCESS_OF
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Child
23. 2019 novel coronavirus PROCESS_OF Patients
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2019 novel coronavirus
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PROCESS_OF
Object
Patients
24. COVID-19 PROCESS_OF Patients
Subject
COVID-19
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PROCESS_OF
Object
Patients
25. Lung LOCATION_OF Biopsy
Subject
Lung
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LOCATION_OF
Object
Biopsy
26. Elderly (population group) LOCATION_OF angiotensin converting enzyme 2
Subject
Elderly (population group)
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
27. Child LOCATION_OF angiotensin converting enzyme 2
Subject
Child
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LOCATION_OF
Object
angiotensin converting enzyme 2
28. Pseudovirus LOCATION_OF angiotensin converting enzyme 2
Subject
Pseudovirus
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LOCATION_OF
Object
angiotensin converting enzyme 2
29. Lymphopenia PROCESS_OF Patients
Subject
Lymphopenia
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PROCESS_OF
Object
Patients
30. Pneumonia PROCESS_OF Patients
Subject
Pneumonia
Predicate
PROCESS_OF
Object
Patients
31. Inflammatory Response PROCESS_OF Patients
Subject
Inflammatory Response
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PROCESS_OF
Object
Patients
32. Patients LOCATION_OF angiotensin converting enzyme 2
Subject
Patients
Predicate
LOCATION_OF
Object
angiotensin converting enzyme 2
33. Tract PART_OF Lung
Subject
Tract
Predicate
PART_OF
Object
Lung
34. COVID-19 CAUSES Pneumonia
Subject
COVID-19
Predicate
CAUSES
Object
Pneumonia
ABSTRACT

BACKGROUND:

Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren't well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients.

METHODS:

We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19.

RESULTS:

Compared with children, older patients (>50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P = .001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P < .01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P < .025).

CONCLUSIONS:

Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Stem Cells / Angiotensin-Converting Enzyme 2 / COVID-19 Type of study: Observational study / Risk factors Limits: Aged / Child / Humans / Middle aged Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2021 Document Type: Article Affiliation country: Cid

Full text: Available Collection: International databases Database: MEDLINE Main subject: Stem Cells / Angiotensin-Converting Enzyme 2 / COVID-19 Type of study: Observational study / Risk factors Limits: Aged / Child / Humans / Middle aged Language: English Journal: Clin Infect Dis Journal subject: Communicable Diseases Year: 2021 Document Type: Article Affiliation country: Cid