Baseline Interleukin-6 Level Predicts Risk of Severe COVID-19: A Two-Center, Retrospective Study (preprint)

ABSTRACT

Background:The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic has affected almost every country. Interleukin-6 (IL-6), a cytokine secreted by CD4+ T cell, has been shown to be a reliable marker of disease severity and a useful parameter for monitoring progression of coronavirus disease-2019 (COVID-19). However its value as a predictor of severe disease has not been assessed.Methods:A total of 160 laboratory-confirmed COVID-19 patients admitted to two hospitals were enrolledand separated into two groups according to whether or not they progressed to develop severe illness. Demographic and clinical characteristics at admission were compared between the groups.Results: Patients who developed severe COVID-19 had significantly higher baseline IL-6 levels than patients who had mild disease course in hospital (P< 0.001). Patients were further grouped according to quartiles of IL-6 level. The cumulative incidence of severe illnesswas significantly higher in the third and fourth quartiles groups than in the first quartile group (55% vs. 15% and 80% vs. 15%, respectively;bothP< 0.001). In multivariate logistic regression analysis, the risk for developing severe disease was markedly higher in the highest IL-6 quartile than in the lowest quartile (odds ratio 14.95; 95% confidence interval 3.65–61.30; P< 0.001). Receiver operating characteristic curve analysis of potential predictive variables showed the area under the curve to be largest for baseline IL-6, with the value of 5.20 pg/mL having the best balance of sensitivity and specificity for predicting risk of severe COVID-19.Conclusion: Serum baseline IL-6 appears to be a reliable predictor of risk of severe COVID-19. Early intervention may be advisable in patients with serum IL-6 levels >5.20 pg/mL, even if initial symptoms are mild.