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The first multi-organ proteomic landscape of COVID-19 autopsies completed by researchers from Westlake University and Union Hospital of Huazhong University of Science and Technology

05, 2021

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On January 9th, Beijing Time, a research paper entitled "Multi-organ Proteomic Landscape of COVID-19 Autopsies" was published online in Cell, reporting on an in-depth multi-organ quantitative proteome of COVID-19 autopsy samples. The report is a piece of joint work between Westlake University and Union Hospital of the Huazhong University of Science and Technology. The molecular landscape helps clinicians and researchers to better understand how and why tissue injuries and multi-organ failure happen in COVID-19 victims.

This is the first comprehensive and systematic proteomics analysis of multi-organ responses to SARS-CoV-2 in COVID-19 patients, promoting molecular understanding of COVID-19 pathology. The study also offers a rich resource for developing therapies against the pandemic. 

Multi-organ injuries, especially pulmonary lesions, have been reported according to the clinical diagnosis and morphological characterization of autopsies. However, most previous mechanistic studies on COVID-19 are based on cell line models to predict the effects of the virus on multiple organs of COVID-19 patients. Few studies have characterized host responses at the molecular level from multiple organs of COVID-19 patients. This has limited our knowledge concerning how the SARS-CoV-2 virus induces injuries in multiple organs, and how to prevent and revert them.

Autopsies from lung, spleen, liver, kidney, heart, testis and thyroid of 19 COVID-19 victims were included in this study. Through the comparisons of proteomic profiling and classical microscopic pathological examination between COVID-19 and non-COVID-19 groups, the team found that the receptor for virus entry, angiotensin-converting enzyme 2 (ACE2), did not show significant regulation in the lung in the study. Interestingly, CTSL, the serine protease of SARS-CoV-2 in the endosomal pathway, was significantly upregulated in the lung. It suggests that ACE2 inhibitors might not be an effective therapy for severe and critical COVID-19 patients, while CTSL could be a potential therapeutic target for COVID-19.

Based on further systemic analysis, the team found that spleen and lung exhibited decreased adaptive immune response patterns. In addition, although the microscopically substantial fibrosis was only exhibited in the lung, the proteome results showed that fibrosis processes have been triggered in multiple organs, including the liver and kidney. The molecular changes might be exploited to instruct tissue fibrosis treatment for COVID-19 patients. This study also provided molecular evidence for testicular injuries, including reduced Leydig cells, inhibited cholesterol biosynthesis, impairment of spermatogenesis and sperm motility. It suggests that the fertility of male COVID-19 patients might be affected. However, this study was based on the tissue samples from COVID-19 autopsies, therefore, further studies are needed to investigate whether the similar changes will exhibit in the mild and severe patients, and whether such changes are reversible.

This study is from the Center for Infectious Disease Research, Westlake Laboratory of Life Sciences and Biomedicine, Westlake University, and Union Hospital the Huazhong University of Science and Technology. Part of the research was assisted by Westlake University Supercomputer Center and the Mass Spectrometry & Metabolomics Core Facility at the Center for Biomedical Research Core Facilities of Westlake University. Tencent Charitable Foundation and Westlake Education Foundation also supported the project.