50-gene risk profiles in peripheral blood predict COVID-19 outcomes: A retrospective, multicenter cohort study
نویسندگان
چکیده
AbstractBackground COVID-19 has been associated with Interstitial Lung Disease features. The immune transcriptomic overlap between Idiopathic Pulmonary Fibrosis (IPF) and not investigated. Methods we analyzed blood transcript levels of 50 genes known to predict IPF mortality in three two cohorts. Scoring Algorithm Molecular Subphenotypes (SAMS) was applied distinguish high versus low-risk profiles all SAMS cutoffs derived from the Discovery cohort were used intensive care unit (ICU) status, need for mechanical ventilation, in-hospital Validation cohort. A Single-cell RNA-sequencing identify cellular sources 50-gene risk profiles. same Findings discriminated severe mild (P = 0·015) predicted ICU admission, (AUC: 0·77, 0·75, 0·74, respectively, P < 0·001) In COVID-19, expressing cells a high-risk profile included monocytes, dendritic cells, neutrophils, while profile-expressing CD4+, CD8+ T lymphocytes, IgG producing plasmablasts, B NK, gamma/delta cells. Same also predictive University Chicago (HR:5·26, 95%CI:1·81–15·27, 0·0013) Imperial College London (HR:4·31, 95%CI:1·81–10·23, 0·0016) Interpretation peripheral outcomes. these gene expression changes suggest common innate adaptive responses both diseases. Funding This work supported part by National Institute Health Research Clinician Scientist Fellowship NIHR: CS-2013-13-017 (TMM); Action Mike Bray fellowship (PLM); Heart, Lung, Blood (NHLBI) through award K01-HL-130704 (AJ); South Florida (USF) Academic Support Fund USF Foundation, Ubben (JHM).
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ژورنال
عنوان ژورنال: EBioMedicine
سال: 2021
ISSN: ['2352-3964']
DOI: https://doi.org/10.1016/j.ebiom.2021.103439