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• W4308174712 abstract "Abstract Defining the molecular mechanisms of novel diseases such as COVID-19 is crucial to identify treatable traits to improve patient care. To circumvent a priori bias and the lack of in-depth knowledge of this new disease, we opted for an unsupervised stratification approach, followed by detailed multi-modal characterization using proteome, metabolomic, genomic, and clinical features. Using the detailed circulating proteome, as measured by 4985 aptamers (SOMAmers), robust consensus clustering identified six endophenotypes (EPs) present among 731 SARS-CoV-2 PCR-positive hospitalized participants to Biobanque québécoise de la COVID-19 (BQC19) , with varying degrees of disease severity and times to intensive care unit (ICU) admission. In particular, one endophenotype, EP6, was associated with a greater proportion of ICU admission, mechanical ventilation, acute respiratory distress syndrome (ARDS) and death. Clinical features of this endophenotype showed increased levels of C-reactive protein, D-dimers, elevated neutrophils, and depleted lymphocytes. Moreover, metabolomic analysis supported a role for immuno-thrombosis in severe COVID-19 ARDS. Furthermore, Fibroblast Growth Factor Receptor (FGFR) and SH2-containing transforming protein 4 (SHC4) signaling were identified as molecular features associated with severe COVID-19. Importantly, a predictive model was developed and validated on an additional set of 631 SARS-CoV-2 PCR-positive patients to enable prediction of these endophenotypes, which reflect patients’ likelihood of admission to ICU, solely based on clinical laboratory measurements. This suggests the use of blood markers as surrogates for generalizing these EPs to new patients and automating identification of high-risk groups in the clinic." @default.
• W4308174712 created "2022-11-08" @default.
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• W4308174712 date "2022-11-04" @default.
• W4308174712 modified "2023-10-18" @default.
• W4308174712 title "Circulating proteome of hospitalized patients uncovers six endophenotypes of COVID-19 and points to FGFR and SHC4-signaling in acute respiratory distress syndrome" @default.
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• W4308174712 doi "https://doi.org/10.1101/2022.11.02.22281834" @default.
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