Multi-organ Proteomic Landscape of COVID-19 Autopsies
Author:
Nie Xiu, Qian Liujia, Sun Rui, Huang Bo, Dong Xiaochuan, Xiao Qi, Zhang Qiushi, Lu Tian, Yue Liang, Chen Shuo, Li Xiang, Sun Yaoting, Li Lu, Xu Luang, Li Yan, Yang Ming, Xue Zhangzhi, Liang Shuang, Ding Xuan, Yuan Chunhui, Peng Li, Liu Wei, Yi Xiao, Lyu Mengge, Xiao Guixiang, Xu Xia, Ge Weigang, He Jiale, Fan Jun, Wu Junhua, Luo Meng, Chang Xiaona, Pan Huaxiong, Cai Xue, Zhou Junjie, Yu Jing, Gao Huanhuan, Xie Mingxing, Wang Sihua, Ruan Guan, Chen Hao, Su Hua, Mei Heng, Luo Danju, Zhao Dashi, Xu Fei, Li Yan, Zhu YiORCID, Xia Jiahong, Hu Yu, Guo Tiannan
Abstract
ABSTRACTThe molecular pathology of multi-organ injuries in COVID-19 patients remains unclear, preventing effective therapeutics development. Here, we report an in-depth multi-organ proteomic landscape of COVID-19 patient autopsy samples. By integrative analysis of proteomes of seven organs, namely lung, spleen, liver, heart, kidney, thyroid and testis, we characterized 11,394 proteins, in which 5336 were perturbed in COVID-19 patients compared to controls. Our data showed that CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients. Dysregulation of protein translation, glucose metabolism, fatty acid metabolism was detected in multiple organs. Our data suggested upon SARS-CoV-2 infection, hyperinflammation might be triggered which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart and thyroid. Evidence for testicular injuries included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility. In summary, this study depicts the multi-organ proteomic landscape of COVID-19 autopsies, and uncovered dysregulated proteins and biological processes, offering novel therapeutic clues.HIGHLIGHTSCharacterization of 5336 regulated proteins out of 11,394 quantified proteins in the lung, spleen, liver, kidney, heart, thyroid and testis autopsies from 19 patients died from COVID-19.CTSL, rather than ACE2, was significantly upregulated in the lung from COVID-19 patients.Evidence for suppression of glucose metabolism in the spleen, liver and kidney; suppression of fatty acid metabolism in the kidney; enhanced fatty acid metabolism in the lung, spleen, liver, heart and thyroid from COVID-19 patients; enhanced protein translation initiation in the lung, liver, renal medulla and thyroid.Tentative model for multi-organ injuries in patients died from COVID-19: SARS-CoV-2 infection triggers hyperinflammatory which in turn induces damage of gas exchange barrier in the lung, leading to hypoxia, angiogenesis, coagulation and fibrosis in the lung, kidney, spleen, liver, heart, kidney and thyroid.Testicular injuries in COVID-19 patients included reduced Leydig cells, suppressed cholesterol biosynthesis and sperm mobility.
Publisher
Cold Spring Harbor Laboratory
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