【文献速递】-Multi-organ Proteomic Lan

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 5336 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 include 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尚不清楚，阻碍了有效治疗方法的发展。在这里，我们对19例COVID-19患者的7个器官的144份尸检样本进行了蛋白质组学分析。我们在这些样本中量化了11394个蛋白质，与对照组相比，COVID-19患者中有5336个蛋白质受到干扰。我们的数据显示，COVID-19患者肺部组织蛋白酶L1显著上调，而不是ACE2。在多器官中检测到全身炎症过度和葡萄糖和脂肪酸代谢失调。我们还观察到COVID-19患者多器官缺氧、血管生成、凝血、纤维化等关键因素的异常调节。睾丸损伤的证据包括睾丸间质细胞减少，胆固醇生物合成抑制和精子灵活性。总之，本研究描绘了COVID-19尸检的多器官蛋白质组学图景，有助于我们进一步理解COVID-19病理学的生物学基础。