Gene Expression Risk Scores for COVID-19 Illness Severity

Authors

Derick R. Peterson
Andrea M. Baran
Edward E. Walsh, Rochester Regional HealthFollow
Ann R. Falsey, Rochester Regional HealthFollow

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

Recommended Citation

Peterson, D. R., Baran, A. M., Walsh, E. E., & Falsey, A. R. (2023). Gene Expression Risk Scores for COVID-19 Illness Severity. Journal of Infectious Diseases, 227 (3), 322-331. https://doi.org/10.1093/infdis/jiab568