Multi-organ Proteomic Landscape of COVID-19 Autopsies

Abstract

The 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.

Role of Multiomics Data to Understand Host–Pathogen Interactions in COVID-19 Pathogenesis

“…In an almost identical approach, the altered proteomic landscape of severe COVID-19 on human tissues was surveyed. 70 Interestingly, they noticed that, rather than ACE2, it was the CTSL protein that was up-regulated in the lungs. Also, glucose metabolism in the spleen, liver, and kidney was suppressed, as was fatty acid metabolism in the kidney.…”

“…Furthermore, functional impairment of Leydig cells and reduced sperm mobility was reported due to down-regulation of cholesterol metabolism, which leads to down-regulation of associated proteins using cholesterol as a precursor. 70 …”

“… 59 Further, lung autopsy samples of patients deceased due to COVID-19 have revealed that the indicators of innate immune response TNF receptor-associated factor 6 (TRAF6), TYRO protein tyrosine kinase binding protein (TYROBP) were up-regulated, as were factors responsible for the pro-inflammatory state. 70 …”

“…Their study showed up-regulation of immune checkpoint proteins CEACAM1, CD276, and CD274 that lead to suppression of adaptive immune function. 70 …”

COVID-19 plasma deep proteome reveals distinct signatures in severe patients

“…However, although SARS-CoV-2 primarily targets the respiratory tract and lung, an increasing body of work has shown the virus to infect other organs like the gastrointestinal tract, liver, kidney, cardiac muscles, central nervous system, musculoskeletal system, and even reproductive system in males. 6,7 The diagnosis of the disease has been accurate and widespread. This was possible due to increased availability and deployment of RT-PCR assays, 8 or serological test kits, and scaling up of testing rates globally.…”