학술논문
A 6-mRNA host response classifier in whole blood predicts outcomes in COVID-19 and other acute viral infections.
Document Type
Article
Author
Buturovic, Ljubomir; Zheng, Hong; Tang, Benjamin; Lai, Kevin; Kuan, Win Sen; Gillett, Mark; Santram, Rahul; Shojaei, Maryam; Almansa, Raquel; Nieto, Jose Ángel; Muñoz, Sonsoles; Herrero, Carmen; Antonakos, Nikolaos; Koufargyris, Panayiotis; Kontogiorgi, Marina; Damoraki, Georgia; Liesenfeld, Oliver; Wacker, James; Midic, Uros; Luethy, Roland
Source
Subject
*COVID-19
*MESSENGER RNA
*GENE amplification
*RESPIRATORY insufficiency
*VIRUS diseases
*INFLUENZA
*LOGISTIC regression analysis
*GENE expression
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Language
ISSN
2045-2322
Abstract
Predicting 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. We developed a logistic regression-based 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. 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 1417 samples across 21 independent retrospective cohorts the locked 6-RNA classifier had an area under curve of 0.94 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. 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. [ABSTRACT FROM AUTHOR]