50-gene risk profiles in peripheral blood predict COVID-19 outcomes: A retrospective, multicenter cohort study.
EBioMedicine
; 69: 103439, 2021 Jul.
Article
in English
| MEDLINE | ID: covidwho-1275277
ABSTRACT
BACKGROUND:
COVID-19 has been associated with Interstitial Lung Disease features. The immune transcriptomic overlap between Idiopathic Pulmonary Fibrosis (IPF) and COVID-19 has not been investigated.METHODS:
we analyzed blood transcript levels of 50 genes known to predict IPF mortality in three COVID-19 and two IPF cohorts. The Scoring Algorithm of Molecular Subphenotypes (SAMS) was applied to distinguish high versus low-risk profiles in all cohorts. SAMS cutoffs derived from the COVID-19 Discovery cohort were used to predict intensive care unit (ICU) status, need for mechanical ventilation, and in-hospital mortality in the COVID-19 Validation cohort. A COVID-19 Single-cell RNA-sequencing cohort was used to identify the cellular sources of the 50-gene risk profiles. The same COVID-19 SAMS cutoffs were used to predict mortality in the IPF cohorts.FINDINGS:
50-gene risk profiles discriminated severe from mild COVID-19 in the Discovery cohort (P = 0·015) and predicted ICU admission, need for mechanical ventilation, and in-hospital mortality (AUC 0·77, 0·75, and 0·74, respectively, P < 0·001) in the COVID-19 Validation cohort. In COVID-19, 50-gene expressing cells with a high-risk profile included monocytes, dendritic cells, and neutrophils, while low-risk profile-expressing cells included CD4+, CD8+ T lymphocytes, IgG producing plasmablasts, B cells, NK, and gamma/delta T cells. Same COVID-19 SAMS cutoffs were also predictive of mortality in the University of Chicago (HR5·26, 95%CI1·81-15·27, P = 0·0013) and Imperial College of London (HR4·31, 95%CI1·81-10·23, P = 0·0016) IPF cohorts.INTERPRETATION:
50-gene risk profiles in peripheral blood predict COVID-19 and IPF outcomes. The cellular sources of these gene expression changes suggest common innate and adaptive immune responses in both diseases.FUNDING:
This work was supported in part by National Institute for Health Research Clinician Scientist Fellowship NIHR CS-2013-13-017 (TMM); Action for Pulmonary Fibrosis Mike Bray fellowship (PLM); The National Heart, Lung, and Blood Institute (NHLBI) through award K01-HL-130704 (AJ); The University of South Florida (USF) Academic Support Fund and the USF Foundation, Ubben Fibrosis Fund (JHM).Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Transcriptome
/
COVID-19
Type of study:
Cohort study
/
Observational study
/
Prognostic study
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Language:
English
Journal:
EBioMedicine
Year:
2021
Document Type:
Article
Affiliation country:
J.ebiom.2021.103439
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