Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Key Laboratory of Structural Biology of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou 310024, China; Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Hangzhou 310024, China; Institute of Basic Medical Sciences, Westlake Institute for Advanced Study, Hangzhou 310024, China.
Cell. 2021 Feb 4;184(3):775-791.e14. doi: 10.1016/j.cell.2021.01.004. Epub 2021 Jan 9.
The molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report a proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients. We quantified 11,394 proteins in these samples, in which 5,336 were perturbed in the COVID-19 patients compared to controls. Our data showed that cathepsin L1, rather than ACE2, was significantly upregulated in the lung from the COVID-19 patients. Systemic hyperinflammation and dysregulation of glucose and fatty acid metabolism were detected in multiple organs. We also observed dysregulation of key factors involved in hypoxia, angiogenesis, blood coagulation, and fibrosis in multiple organs from the COVID-19 patients. Evidence for testicular injuries includes reduced Leydig cells, suppressed cholesterol biosynthesis, and sperm mobility. In summary, this study depicts a multi-organ proteomic landscape of COVID-19 autopsies that furthers our understanding of the biological basis of COVID-19 pathology.
COVID-19 患者多器官损伤的分子病理学仍不清楚,这阻碍了有效的治疗方法的发展。在这里,我们报告了对 COVID-19 患者的 19 例 7 个器官的 144 个尸检样本的蛋白质组学分析。我们对这些样本中的 11394 种蛋白质进行了定量分析,其中 5336 种蛋白质在 COVID-19 患者中与对照组相比发生了改变。我们的数据表明,COVID-19 患者肺组织中的组织蛋白酶 L1 而不是 ACE2 显著上调。在多个器官中检测到全身性炎症反应过度和葡萄糖及脂肪酸代谢失调。我们还观察到 COVID-19 患者多个器官中与缺氧、血管生成、血液凝固和纤维化相关的关键因素失调。睾丸损伤的证据包括莱迪希细胞减少、胆固醇生物合成抑制和精子活动力降低。总之,本研究描绘了 COVID-19 尸检的多器官蛋白质组图谱,进一步了解了 COVID-19 病理学的生物学基础。