61
IRUS TotalDownloads
Altmetric
50-gene risk profiles in peripheral blood predict COVID-19 outcomes: A retrospective, multicenter cohort study
File | Description | Size | Format | |
---|---|---|---|---|
1-s2.0-S2352396421002322-main.pdf | Published version | 2.92 MB | Adobe PDF | View/Open |
Title: | 50-gene risk profiles in peripheral blood predict COVID-19 outcomes: A retrospective, multicenter cohort study |
Authors: | Juan Guardela, BM Sun, J Zhang, T Xu, B Balnis, J Huang, Y Ma, S-F Molyneaux, PL Maher, TM Noth, I Michaud, G Jaitovich, A Herazo-Maya, JD |
Item 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. |
Issue Date: | 1-Jul-2021 |
Date of Acceptance: | 1-Jun-2021 |
URI: | http://hdl.handle.net/10044/1/89861 |
DOI: | 10.1016/j.ebiom.2021.103439 |
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/Funder: | National Institute for Health Research British Lung Foundation Action for Pulmonary Fibrosis |
Funder's Grant Number: | CS-2013-13-017 C17-3 n/a |
Keywords: | 50-gene risk profiles COVID-19 Dendritic Cells and Neutrophils IPF Monocytes Mortality 50-gene risk profiles COVID-19 Dendritic Cells and Neutrophils IPF Monocytes Mortality 1103 Clinical Sciences 1117 Public Health and Health Services |
Publication Status: | Published |
Conference Place: | Netherlands |
Article Number: | ARTN 103439 |
Online Publication Date: | 2021-06-20 |
Appears in Collections: | National Heart and Lung Institute Imperial College London COVID-19 |
This item is licensed under a Creative Commons License