Novel insight from the first lung transplant of a COVID-19 patient
Novel insight from the first lung transplant of a COVID-19 patient
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DOI：
10.1111/eci.13443
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发表时间：
2020-11-20
影响因子：
5.5
通讯作者：
Chen, Feng
中科院分区：
文献类型：
--
作者：
Chen, Xiao-Jun;Li, Kai;Chen, Feng
背景为揭示SARS-CoV-2在全球首例成功的新冠肺炎肺移植患者肺组织中的组织病理学变化、病毒分布、免疫学特性和多组学特征。用光学显微镜和透射电子显微镜观察组织病理学特征和病毒分布。免疫细胞检测采用流式细胞仪和免疫组织化学方法。采用转录组和蛋白质组方法研究新冠肺炎肺纤维化的主要生物学过程。结果肺组织病理变化以广泛的肺间质纤维化和出血为特征。巨噬细胞胞浆内可见病毒颗粒。肺内CD3(+)、CD4(-)T细胞、中性粒细胞、NK细胞、γ/Delta T细胞和单核细胞较多，B细胞较少。促炎症细胞因子iNOS、IL-1β和IL-6水平在轻度纤维化区域较高。多组学分析显示，在20,356例轻度和重度肺纤维化患者肺组织中，共发现了126个显著差异转录和8,493个蛋白表达，其中大部分与纤维化和炎症有关。结论新冠肺炎患者肺组织中性粒细胞/CD_3(+)CD_4(-)T细胞/巨噬细胞的显著激活导致了细胞因子风暴和严重纤维化，这可能有助于更好地理解新冠肺炎的发病机制。
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, gamma/delta T cells and monocytes, but not B cells, were abundant in the lungs. Higher levels of proinflammatory cytokines iNOS, IL-1 beta 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.