1. Dysregulated proteasome activity and steroid hormone biosynthesis are associated with mortality among patients with acute COVID-19.
- Author
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Liu F, Yang H, Yang T, Zhang Z, Guan L, Gao L, Ma H, Zhang H, Song N, Tong Z, and Li J
- Subjects
- Humans, Male, Female, Middle Aged, Aged, SARS-CoV-2, Prognosis, Adult, Steroids biosynthesis, Steroids blood, Acute Disease, Case-Control Studies, Machine Learning, COVID-19 mortality, COVID-19 blood, Proteasome Endopeptidase Complex metabolism, Biomarkers blood
- Abstract
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 metabolite (urocortisone), to predict mortality among COVID-19 patients (area under the receiver operating characteristic curve: 0.976) on the first day of hospitalization. Our systematic analysis provides a novel method for the early prediction of mortality in hospitalized COVID-19 patients., (© 2024. The Author(s).)
- Published
- 2024
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