• Xiao-Jun Chen, Kai Li, Lei Xu, You-Jia Yu, Bo Wu, Yuan-Lin He, Wen-E Zhao, Ding Li, Chang-Xing Luan, Li Hu, Jie Wang, Jing-Jing Ding, Yan-Fang Yu, Jing-Xin Li, Zhong-Ming Tan, Xiao-Fei Liu, Dong Wei, Zhi-Hong Zhang, Xue-Jiang Guo, Chuan Su, Zhi-Bin Hu, Yue-Shuai Guo, Jing-Yu Chen, and Feng Chen.
• Department of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Pathogen Biology, Nanjing Medical University, Nanjing, China.
• Eur. J. Clin. Invest. 2021 Jan 1; 51 (1): e13443.

BackgroundTo 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 MethodsA 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.ResultsThe 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.ConclusionsOur 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.© 2020 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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