Inflammatory phenotyping predicts clinical outcome in COVID-19
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RESEARCH
Open Access
Inflammatory phenotyping predicts clinical outcome in COVID-19 H. Burke1,2*†, A. Freeman1,2†, D. C. Cellura1, B. L. Stuart3, N. J. Brendish1,2, S. Poole1,2,4, F. Borca2,5, H. T. T. Phan3,5, N. Sheard2, S. Williams2, C. M. Spalluto1, K. J. Staples1,2,3,6, T. W. Clark1,2,3,7†, T. M. A. Wilkinson1,2† and on behalf of the REACT COVID investigators
Abstract Background: The COVID-19 pandemic has led to more than 760,000 deaths worldwide (correct as of 16th August 2020). Studies suggest a hyperinflammatory response is a major cause of disease severity and death. Identitfying COVID-19 patients with hyperinflammation may identify subgroups who could benefit from targeted immunomodulatory treatments. Analysis of cytokine levels at the point of diagnosis of SARS-CoV-2 infection can identify patients at risk of deterioration. Methods: We used a multiplex cytokine assay to measure serum IL-6, IL-8, TNF, IL-1β, GM-CSF, IL-10, IL-33 and IFN-γ in 100 hospitalised patients with confirmed COVID-19 at admission to University Hospital Southampton (UK). Demographic, clinical and outcome data were collected for analysis. Results: Age > 70 years was the strongest predictor of death (OR 28, 95% CI 5.94, 139.45). IL-6, IL-8, TNF, IL-1β and IL-33 were significantly associated with adverse outcome. Clinical parameters were predictive of poor outcome (AUROC 0.71), addition of a combined cytokine panel significantly improved the predictability (AUROC 0.85). In those ≤70 years, IL-33 and TNF were predictive of poor outcome (AUROC 0.83 and 0.84), addition of a combined cytokine panel demonstrated greater predictability of poor outcome than clinical parameters alone (AUROC 0.92 vs 0.77). Conclusions: A combined cytokine panel improves the accuracy of the predictive value for adverse outcome beyond standard clinical data alone. Identification of specific cytokines may help to stratify patients towards trials of specific immunomodulatory treatments to improve outcomes in COVID-19. Keywords: COVID-19, SARS-CoV-2, IL-33, TNF-α, Point-of-care testing
Background Coronavirus disease 2019 (COVID-19) has been confirmed in 21,294,845 people worldwide as of 16th August 2020, carrying a mortality of nearly 4%, compared with a mortality rate of less than 1% from influenza [1]. Although this mortality rate maybe an overestimation due to lack of * Correspondence: [email protected] † H. Burke, A. Freeman, T. W. Clark and T. M. A. Wilkinson contributed equally to this work. 1 School of Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton General Hospital, LF13A, South Academic Block, Southampton SO16 6YD, UK 2 University Hospitals Southampton NHS Foundation Trust, Southampton, UK Full list of author information is available at the end of the article
adequate testing among other factors, currently more than 760,000 deaths are attributed to COVID-19 and therefore there is an urgent need for effective treatment. Accumulating evidence suggests that in addition to direct viral damage, uncontrolled
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