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EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-311148


Early recognition of risk and start of treatment may improve unfavorable outcome of COVID-19. In the SAVE-MORE double-blind randomized trial, 594 patients with pneumonia without respiratory dysfunction at risk as defined by plasma suPAR (soluble urokinase plasminogen activator receptor) ≥ 6 ng/ml were 1:2 randomized to subcutaneous placebo or 100 mg anakinra once daily for 10 days;85.9% were co-administered dexamethasone. After 28 days, anakinra-treated patients were distributed to lower strata of the 11-point World Health Organization ordinal Clinical Progression Scale (WHO-CPS) (adjusted odds ratio-OR 0.36;95%CI 0.26–0.50;P < 0.001);anakinra protected from severe disease or death (≥ 6 points of WHO-CPS) (OR: 0.46;P: 0.010). The median WHO-CPS decrease in the placebo and anakinra groups was 3 and 4 points (OR 0.40;P < 0.0001);the median decrease of SOFA score was 0 and 1 points (OR 0.63;P: 0.004). 28-day mortality decreased (hazard ratio: 0.45;P: 0.045) and hospital stay was shorter. (Sponsored by the Hellenic Institute for the Study of Sepsis identifier, NCT04680949)

Sci Rep ; 12(1): 889, 2022 01 18.
Article in English | MEDLINE | ID: covidwho-1630723


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.

COVID-19 , Gene Expression Regulation , RNA, Messenger/blood , SARS-CoV-2/metabolism , Acute Disease , COVID-19/blood , COVID-19/mortality , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Retrospective Studies