50-gene risk profiles in peripheral blood predict COVID-19 outcomes: A retrospective, multicenter cohort study

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 frommild 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. (C) 2021 The Authors. Published by Elsevier B.V.

Automated summary

Blood transcript levels of 50 genes can be used to predict outcomes in COVID-19 and IPF patients, suggesting common immune responses in both diseases. The 50-gene risk profiles are effective in distinguishing severe from mild COVID-19 and predicting disease progression and mortality.