Gene Expression Risk Scores for COVID-19 Illness Severity

Peterson, D. R.; Baran, A. M.; Bhattacharya, S.; Branche, A. R.; Croft, D. P.; Corbett, A. M.; Walsh, E. E.; Falsey, A. R.; Mariani, T. J.

doi:10.1101/2021.08.24.457521

bioRxiv · 10.1101/2021.08.24.457521

Gene Expression Risk Scores for COVID-19 Illness Severity

Peterson, D. R.·Baran, A. M.·Bhattacharya, S.·Branche, A. R.·Croft, D. P.·Corbett, A. M.·Walsh, E. E.·Falsey, A. R.·Mariani, T. J.

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Abstract

BackgroundThe correlates of COVID-19 illness severity following infection with SARS-Coronavirus 2 (SARS-CoV-2) are incompletely understood. MethodsWe 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 non-severe COVID. ResultsGene expression patterns in participants with mild and moderate illness were similar, but significantly different from severe illness. When comparing severe versus non-severe illness, we identified >4000 genes differentially expressed (FDR<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 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. ConclusionThese data suggest that gene expression classifiers may provide clinical utility as predictors of COVID-19 illness severity.

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Peterson, D. R., Baran, A. M., Bhattacharya, S., Branche, A. R., Croft, D. P., Corbett, A. M., Walsh, E. E., Falsey, A. R., Mariani, T. J.. 2021-08-24. Gene Expression Risk Scores for COVID-19 Illness Severity. https://doi.org/10.1101/2021.08.24.457521

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