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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.
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1 Inflammatix, Inc., Burlingame, USA
2 Stanford University, Institute for Immunity, Transplantation and Infection, School of Medicine, Palo Alto, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Stanford University, Center for Biomedical Informatics Research, Department of Medicine, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956)
3 Westmead Institute for Medical Research, Centre for Immunology and Allergy Research, Sydney, Australia (GRID:grid.452919.2) (ISNI:0000 0001 0436 7430); Nepean Hospital, Department of Intensive Care Medicine, Sydney, Australia (GRID:grid.413243.3) (ISNI:0000 0004 0453 1183); University of Sydney, Nepean Genomic Research Group, Nepean Clinical School, Sydney, Australia (GRID:grid.1013.3) (ISNI:0000 0004 1936 834X); Marie Bashir Institute for Infectious Diseases and Biosecurity, Sydney, Australia (GRID:grid.1013.3)
4 Westmead Hospital, Department of Emergency Medicine, Sydney, Australia (GRID:grid.413252.3) (ISNI:0000 0001 0180 6477)
5 National University Hospital Singapore, Department of Emergency Medicine, Singapore, Singapore (GRID:grid.412106.0) (ISNI:0000 0004 0621 9599)
6 Royal North Shore Hospital, Department of Emergency Medicine, Sydney, Australia (GRID:grid.412703.3) (ISNI:0000 0004 0587 9093)
7 St Vincent Hospital, Department of Emergency Medicine, Sydney, Australia (GRID:grid.412703.3)
8 Westmead Institute for Medical Research, Centre for Immunology and Allergy Research, Sydney, Australia (GRID:grid.452919.2) (ISNI:0000 0001 0436 7430); Nepean Hospital, Department of Intensive Care Medicine, Sydney, Australia (GRID:grid.413243.3) (ISNI:0000 0004 0453 1183)
9 Instituto de Investigación Biomédica de Salamanca (IBSAL), Group for Biomedical Research in Sepsis (BioSepsis), Salamanca, Spain (GRID:grid.452531.4); Hospital Universitario Río Hortega, Valladolid, Spain (GRID:grid.411280.e) (ISNI:0000 0001 1842 3755)
10 Servicio de Urgencias de Atención Primaria, Salamanca, Spain (GRID:grid.411280.e)
11 National and Kapodistrian University of Athens, Medical School, 4th Department of Internal Medicine, Athens, Greece (GRID:grid.5216.0) (ISNI:0000 0001 2155 0800)
12 Inflammatix, Inc., Burlingame, USA (GRID:grid.5216.0)
13 Stanford University, Institute for Immunity, Transplantation and Infection, School of Medicine, Palo Alto, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Stanford University, Cancer Biology Program, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956)
14 Stanford University, Institute for Immunity, Transplantation and Infection, School of Medicine, Palo Alto, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Stanford University, Immunology Program, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956)
15 Stanford University, Institute for Immunity, Transplantation and Infection, School of Medicine, Palo Alto, USA (GRID:grid.168010.e) (ISNI:0000000419368956); Stanford University, Division of Critical Care Medicine, Department of Pediatrics, School of Medicine, Stanford, USA (GRID:grid.168010.e) (ISNI:0000000419368956)