Zhao Zhang1,2, Liyan Guo1, Li Huang1,3, Che Zhang4, Ruibang Luo5, Liang Zeng6, Huiying Liang7, Qiuhui Li5, Xiaoxia Lu8, Xianfeng Wang9, Chui Yan Ma2, Jianbo Shao9, Weiren Luo10, Le Li11, Li Liu12, Ziyue Li1, Xiaoya Zhou1, Xiaoxian Zhang1, Jie Liu1, Jinjuan Yang1, Ka Yi Kwan12, Wei Liu11, Yi Xu13, Hua Jiang14, Hongsheng Liu15, Hui Du8, Yanheng Wu16, Guangyin Yu17, Junhui Chen18, Jieying Wu1, Jinqiu Zhang1, Can Liao1, Huanhuan Joyce Chen19, Zhiwei Chen12, Hung-Fat Tse2,20,21,22, Huimin Xia7, Qizhou Lian1,7,21. 1. Prenatal Diagnostic Centre and Cord Blood Bank, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. 2. CardiologyDivision,Department of Medicine, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China. 3. Institute of Drug Clinical Trial, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, Hubei, China. 4. Department of Pediatrics, Affiliated Taihe Hospital of Hubei University of Medicine, Shiyan, Hubei, China. 5. Department of Computer Science, the University of Hong Kong, Hong Kong SAR, China. 6. Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. 7. Guangdong Provincial Children's Medical Research Center, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. 8. Department of Respiratory Medicine, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 9. Department of Pediatrics, Third People's Hospital of Shenzhen, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. 10. Department of Pathology, Third People's Hospital of Shenzhen, Second Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China. 11. Department of Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. 12. AIDS Institute and Department of Microbiology, Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong SAR, China. 13. Department of Emergency Medicine, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. 14. Department of Hematology & Oncology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. 15. Department of Radiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. 16. Australian Institute for Bioengineering and Nanotechnology (AIBN), the University of Queensland, Brisbane, Australia. 17. Department of Pathology, Peking University Shenzhen Hospital, Shenzhen, China. 18. Intervention and Cell Therapy Centre, Peking University Shenzhen Hospital, Shenzhen, China. 19. The Pritzker school of Molecular Engineering, the Ben May department of Cancer Research, the University of Chicago, Chicago, Illinois, USA. 20. Division of Cardiology, Department of Medicine, the University of Hong Kong Shenzhen Hospital, Shenzhen, China. 21. Shenzhen Institutes of Research and Innovation, the University of Hong Kong, Shenzhen, China. 22. Hong Kong-Guangdong Joint Laboratory on Stem Cell and Regenerative Medicine, the University of Hong Kong, Hong Kong SAR, China.
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.
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.
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