Gene Expression Risk Scores for COVID-19 Illness Severity

Department

Infectious Diseases

Document Type

Article

Publication Title

Journal of Infectious Diseases

Abstract

Background: The correlates of coronavirus disease 2019 (COVID-19) illness severity following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are incompletely understood.

Methods: We assessed peripheral blood gene expression in 53 adults with confirmed SARS-CoV-2 infection clinically adjudicated as having mild, moderate, or severe disease. Supervised principal components analysis was used to build a weighted gene expression risk score (WGERS) to discriminate between severe and nonsevere COVID-19.

Results: Gene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus nonsevere illness, we identified > 4000 genes differentially expressed (false discovery rate < 0.05). Biological pathways increased in severe COVID-19 were associated with platelet activation and coagulation, and those significantly decreased with T-cell signaling and differentiation. A WGERS based on 18 genes distinguished severe illness in our training cohort (cross-validated receiver operating characteristic-area under the curve [ROC-AUC] = 0.98), and need for intensive care in an independent cohort (ROC-AUC = 0.85). Dichotomizing the WGERS yielded 100% sensitivity and 85% specificity for classifying severe illness in our training cohort, and 84% sensitivity and 74% specificity for defining the need for intensive care in the validation cohort.

Conclusions: These data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity.

First Page

322

Last Page

331

DOI

10.1093/infdis/jiab568

Volume

227

Issue

3

Publication Date

2-1-2023

Comments

See full list of authors at journal website.

Record updated with published article citation 2023-02-09 LB.

Published online ahead of print 2021-11-30.

PubMed ID

34850892

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