A 6-mRNA host response whole-blood classifier trained on pre-pandemic data accurately predicts severity in COVID-19 and other acute viral infections
Abstract
Background
Determining the severity of COVID-19 remains an unmet medical need. Our objective was to develop a blood-based host-gene-expression classifier for the severity of viral infections and validate it in independent data, including COVID-19.
Methods
We developed the classifier for the severity of viral infections and validated it in multiple viral infection settings including COVID-19. We used training data (N=705) from 21 retrospective transcriptomic clinical studies of influenza and other viral illnesses looking at a preselected panel of host immune response messenger RNAs.
Results
We selected 6 host RNAs and trained logistic regression classifier with a cross-validation area under curve of 0.90 for predicting 30-day mortality in viral illnesses. Next, in 1,417 samples across 21 independent retrospective cohorts the locked 6-RNA classifier had an area under curve of 0.91 for discriminating patients with severe vs. non-severe infection. Next, in independent cohorts of prospectively (N=97) and retrospectively (N=100) enrolled patients with confirmed COVID-19, the classifier had an area under curve of 0.89 and 0.87, respectively, for identifying patients with severe respiratory failure or 30-day mortality. Finally, we developed a loop-mediated isothermal gene expression assay for the 6-messenger-RNA panel to facilitate implementation as a rapid assay.
Conclusions
With further study, the classifier could assist in the risk assessment of COVID-19 and other acute viral infections patients to determine severity and level of care, thereby improving patient management and reducing healthcare burden.
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