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Multi-organ proteomic landscape of COVID-19 autopsies.

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. 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; Westlake Omics (Hangzhou) Biotechnology Co., Ltd., Hangzhou 310024, 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; Department of Anatomy, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Department of Anatomy, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China. Department of Anatomy and Physiology, College of Basic Medical Sciences, Shanghai Jiao Tong University, Shanghai 200025, 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. Electronic address: zhuyi@westlake.edu.cn. Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: jiahong.xia@hust.edu.cn. Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: dr_huyu@126.com. 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. Electronic address: guotiannan@westlake.edu.cn.

Cell. 2021;(3):775-791.e14
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Abstract

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.

Methodological quality

Publication Type : Clinical Trial ; Multicenter Study

Metadata

MeSH terms : Proteome ; SARS-CoV-2