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?:abstract
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OBJECTIVE 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 hemorrhage. Viral particles were observed in the cytoplasm of macrophages. CD3+ CD4- T cells 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.
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