Novel insight from the first lung transplant of a COVID‐19 patient

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...

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Published in:	European journal of clinical investigation Vol. 51; no. 1; pp. e13443 - n/a
Main Authors:	Chen, Xiao‐Jun, Li, Kai, Xu, Lei, Yu, You‐Jia, Wu, Bo, He, Yuan‐Lin, Zhao, Wen‐E., Li, Ding, Luan, Chang‐Xing, Hu, Li, Wang, Jie, Ding, Jing‐Jing, Yu, Yan‐Fang, Li, Jing‐Xin, Tan, Zhong‐Ming, Liu, Xiao‐Fei, Wei, Dong, Zhang, Zhi‐Hong, Guo, Xue‐Jiang, Su, Chuan, Hu, Zhi‐Bin, Guo, Yue‐Shuai, Chen, Jing‐Yu, Chen, Feng
Format:	Journal Article
Language:	English
Published:	England Blackwell Publishing Ltd 01-01-2021
Subjects:	B-Lymphocytes - pathology B-Lymphocytes - ultrastructure B-Lymphocytes - virology Biological activity CD3 antigen CD4 antigen Cell activation Chromatography, Liquid COVID-19 COVID-19 - genetics COVID-19 - metabolism COVID-19 - pathology COVID-19 - surgery Cytokine storm Cytokines Cytoplasm Fibrosis Flow Cytometry Gene expression Gene Expression Profiling Hemorrhage Hemorrhage - pathology Humans Immune system Immunohistochemistry Inflammation Interleukin-1beta - metabolism Interleukin-6 - metabolism Killer Cells, Natural - pathology Killer Cells, Natural - ultrastructure Killer Cells, Natural - virology Leukocytes (neutrophilic) Lung - metabolism Lung - pathology Lung - ultrastructure Lung - virology Lung diseases Lung Transplantation Lungs Lymph Nodes - metabolism Lymph Nodes - pathology Lymph Nodes - ultrastructure Lymph Nodes - virology Lymphocytes Lymphocytes B Lymphocytes T Macrophages Macrophages, Alveolar - pathology Macrophages, Alveolar - ultrastructure Macrophages, Alveolar - virology Male Middle Aged Monocytes Monocytes - pathology Monocytes - ultrastructure Monocytes - virology Neutrophils - pathology Neutrophils - ultrastructure Neutrophils - virology Nitric Oxide Synthase Type II - metabolism Nitric-oxide synthase Optical microscopes Pathogenesis pathology Proteomes Proteomics Pulmonary Fibrosis - genetics Pulmonary Fibrosis - metabolism Pulmonary Fibrosis - pathology Pulmonary Fibrosis - surgery RNA-Seq SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 Severity of Illness Index T-Lymphocytes - pathology T-Lymphocytes - ultrastructure T-Lymphocytes - virology Tandem Mass Spectrometry Transcription Transplantation Transplants & implants Viral diseases Viruses COVID-19 SARS-CoV-2 lung transplantation pathology inflammation
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Summary:	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.
Bibliography:	ObjectType-Case Study-2 SourceType-Scholarly Journals-1 ObjectType-Feature-4 content type line 23 ObjectType-Report-1 ObjectType-Article-3
ISSN:	0014-2972 1365-2362
DOI:	10.1111/eci.13443