50-gene risk profiles in peripheral blood predict COVID-19 outcomes: A retrospective, multicenter cohort study
File(s)
Published version
Author(s)
Type
Journal Article
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 (HR:5·26, 95%CI:1·81-15·27, P = 0·0013) and Imperial College of London (HR:4·31, 95%CI:1·81-10·23, 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.
Date Issued
2021-07-01
Date Acceptance
2021-06-01
Citation
EBioMedicine, 2021, 69
ISSN
2352-3964
Publisher
Elsevier
Journal / Book Title
EBioMedicine
Volume
69
Copyright Statement
© 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
Sponsor
National Institute for Health Research
British Lung Foundation
Action for Pulmonary Fibrosis
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/34157486
PII: S2352-3964(21)00232-2
Grant Number
CS-2013-13-017
C17-3
n/a
Subjects
50-gene risk profiles
COVID-19
Dendritic Cells and Neutrophils
IPF
Monocytes
Mortality
Publication Status
Published
Coverage Spatial
Netherlands
Article Number
ARTN 103439
Date Publish Online
2021-06-20