Dysregulated proteasome activity and steroid hormone biosynthesis are associated with mortality among patients with acute COVID-19

作者：Fengjiao Liu, Huqin Yang, Tingyu Yang, Zhijin Zhang, Lujia Guan, Leyi Gao, Haomiao Ma, Haifan Zhang, Nan Song, Zhaohui Tong, Jieqiong Li · 发表于：Journal of Translational Medicine · 年份：2024 · DOI：10.1186/s12967-024-05342-0 · 被引用次数：6 · 研究领域：COVID-19 Clinical Research Studies、Long-Term Effects of COVID-19、SARS-CoV-2 and COVID-19 Research

The persistence of coronavirus disease 2019 (COVID-19)-related hospitalization severely threatens medical systems worldwide and has increased the need for reliable detection of acute status and prediction of mortality. We applied a systems biology approach to discover acute-stage biomarkers that could predict mortality. A total 247 plasma samples were collected from 103 COVID-19 (52 surviving COVID-19 patients and 51 COVID-19 patients with mortality), 51 patients with other infectious diseases (IDCs) and 41 healthy controls (HCs). Paired plasma samples were obtained from survival COVID-19 patients within 1 day after hospital admission and 1-3 days before discharge. There were clear differences between COVID-19 patients and controls, as well as substantial differences between the acute and recovery phases of COVID-19. Samples from patients in the acute phase showed suppressed immunity and decreased steroid hormone biosynthesis, as well as elevated inflammation and proteasome activation. These findings were validated by enzyme-linked immunosorbent assays and metabolomic analyses in a larger cohort. Moreover, excessive proteasome activity was a prominent signature in the acute phase among patients with mortality, indicating that it may be a key cause of poor prognosis. Based on these features, we constructed a machine learning panel, including four proteins [C-reactive protein (CRP), proteasome subunit alpha type (PSMA)1, PSMA7, and proteasome subunit beta type (PSMB)1)] and one...