Xiao-Jun Chen1, Kai Li2, Lei Xu1, You-Jia Yu2, Bo Wu3, Yuan-Lin He4, Wen-E Zhao5, Ding Li2, Chang-Xing Luan2, Li Hu2, Jie Wang2, Jing-Jing Ding2, Yan-Fang Yu2, Jing-Xin Li6, Zhong-Ming Tan6, Xiao-Fei Liu4, Dong Wei3, Zhi-Hong Zhang7, Xue-Jiang Guo4, Chuan Su1, Zhi-Bin Hu4,8, Yue-Shuai Guo4, Jing-Yu Chen3, Feng Chen2,9. 1. Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, China. 2. Department of Forensic Medicine, Nanjing Medical University, Nanjing, China. 3. Wuxi Lung Transplantation Center, Wuxi People's Hospital Affiliated with Nanjing Medical University, Wuxi, China. 4. State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China. 5. Analysis & Test Center, Nanjing Medical University, Nanjing, China. 6. Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China. 7. Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China. 8. Department of Epidemiology, Nanjing Medical University, Nanjing, China. 9. Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing, China.
Abstract
BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19 patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1β and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19 patient and may contribute to a better understanding of COVID-19 pathogenesis.
BACKGROUND: To reveal detailed histopathological changes, virus distributions, immunologic properties and multi-omic features caused by SARS-CoV-2 in the explanted lungs from the world's first successful lung transplantation of a COVID-19patient. MATERIALS AND METHODS: A total of 36 samples were collected from the lungs. Histopathological features and virus distribution were observed by optical microscope and transmission electron microscope (TEM). Immune cells were detected by flow cytometry and immunohistochemistry. Transcriptome and proteome approaches were used to investigate main biological processes involved in COVID-19-associated pulmonary fibrosis. RESULTS: The histopathological changes of the lung tissues were characterized by extensive pulmonary interstitial fibrosis and haemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells, neutrophils, NK cells, γ/δ T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1β and IL-6 were in the area of mild fibrosis. Multi-omics analyses revealed a total of 126 out of 20,356 significant different transcription and 114 out of 8,493 protein expression in lung samples with mild and severe fibrosis, most of which were related to fibrosis and inflammation. CONCLUSIONS: Our results provide novel insight that the significant neutrophil/ CD3+ CD4- T cell/ macrophage activation leads to cytokine storm and severe fibrosis in the lungs of COVID-19patient and may contribute to a better understanding of COVID-19 pathogenesis.
Authors: Isabella S Florissi; Eric W Etchill; Iulia Barbur; Katherine G Verdi; Christian Merlo; Errol L Bush Journal: Semin Thorac Cardiovasc Surg Date: 2022-08-28
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