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Updated: Nov 19, 2025
A Streamlined Approach for Mass Spectrometry-Based Proteomics Using Selected Tissue Regions
Published on: April 18, 2025
Multi-organ proteomic landscape of COVID-19 autopsies
Xiu Nie1, Liujia Qian2, Rui Sun2
1Department of Pathology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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.
Insights
This study analyzed proteins in COVID-19 autopsy samples, revealing widespread organ damage and metabolic changes. Cathepsin L1, not ACE2, was elevated in lungs, highlighting new therapeutic targets for multi-organ injury.
Area of Science:
- * Molecular pathology
- * Proteomics
- * COVID-19 research
Background:
- * The molecular mechanisms underlying multi-organ injuries in COVID-19 are not fully understood.
- * This knowledge gap hinders the development of effective therapeutics.
- * Autopsy studies provide crucial insights into disease pathology.
Purpose of the Study:
- * To conduct a comprehensive proteomic analysis of multiple organs from COVID-19 deceased patients.
- * To identify key molecular alterations and pathways involved in COVID-19 multi-organ pathology.
- * To elucidate the proteomic landscape of COVID-19 autopsy samples.
Main Methods:
- * Proteomic analysis of 144 autopsy samples from seven organs in 19 COVID-19 patients.
- * Quantification of over 11,000 proteins.
- * Comparison of protein expression profiles between COVID-19 patients and controls.
Main Results:
- * 5,336 proteins were perturbed in COVID-19 patients compared to controls.
- * Cathepsin L1 was significantly upregulated in the lung, while ACE2 was not.
- * Systemic hyperinflammation, metabolic dysregulation (glucose, fatty acid), and altered hypoxia, angiogenesis, coagulation, and fibrosis factors were observed across multiple organs.
- * Specific testicular injuries including reduced Leydig cells, suppressed cholesterol biosynthesis, and impaired sperm mobility were identified.
Conclusions:
- * This study provides a detailed multi-organ proteomic landscape of COVID-19 autopsies.
- * Findings reveal systemic hyperinflammation and metabolic dysregulation as key features of severe COVID-19.
- * The identification of upregulated cathepsin L1 in the lung suggests its potential role in COVID-19 lung pathology.
- * The observed testicular injuries highlight the systemic impact of the virus.
