Profiling serum cytokines in COVID-19 patients reveals IL-6 and IL-10 are disease severity predictors

Abstract

Since the outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, it has rapidly spread across many other countries. While the majority of patients were considered mild, critically ill patients involving respiratory failure and multiple organ dysfunction syndrome are not uncommon, which could result death. We hypothesized that cytokine storm is associated with severe outcome. We enrolled 102 COVID-19 patients who were admitted to Renmin Hospital (Wuhan, China). All patients were classified into moderate, severe and critical groups according to their symptoms. 45 control samples of healthy volunteers were also included. Inflammatory cytokines and C-Reactive Protein (CRP) profiles of serum samples were analyzed by specific immunoassays. Results showed that COVID-19 patients have higher serum level of cytokines (TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10) and CRP than control individuals. Within COVID-19 patients, serum IL-6 and IL-10 levels are significantly higher in critical group (n = 17) than in moderate (n = 42) and severe (n = 43) group. The levels of IL-10 is positively correlated with CRP amount (r = 0.41, P < 0.01). Using univariate logistic regression analysis, IL-6 and IL-10 are found to be predictive of disease severity and receiver operating curve analysis could further confirm this result (AUC = 0.841, 0.822 respectively). Our result indicated higher levels of cytokine storm is associated with more severe disease development. Among them, IL-6 and IL-10 can be used as predictors for fast diagnosis of patients with higher risk of disease deterioration. Given the high levels of cytokines induced by SARS-CoV-2, treatment to reduce inflammation-related lung damage is critical.

Keywords: COVID-19; Interleukin 10; Interleukin 6; SARS-CoV-2; cytokine storm; inflammatory cytokines.

Figure 1.

The levels of cytokines in COVID-19 patients and controls. The serum concentration of TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10 from 102 COVID-19 patients and 42 controls were analyzed immediately after hospital admission. Median with range were presented.

Figure 2.

The levels of cytokines in COVID-19 patients with different severity. 102 COVID-19 patients were divided into three groups: moderate, severe and critical. The serum concentration of TNF-α, IFN-γ, IL-2, IL-4, IL-6 and IL-10 were analyzed. Median with range were presented.

Figure 3.

The kinetics of cytokines and CRP in COVID-19 patients during hospitalization. The serum cytokines levels and CRP of moderate, severe and critical patients during hospitalization were presented. The x-axis represents days after admission. Median with range were presented.

Figure 4.

The relationship between CRP and IL-10. Spearman rank correlation analysis was performed to evaluate the correlation of serum IL-10with CRP in the patients with COVID-19.

Figure 5.

ROC curve of cytokines and CRP. Univariate logistic regression analysis was conducted. Performance of ROC curves of TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10 and CRP for predicting COVID-19.

Figure 6.

ROC curve for diagnosis of severe and critical patients with COVID-19. Univariate logistic regression analysis was used to identify the severe and critical patients from controls and moderate COVID-19 patients. Performance of ROC curves of TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10 and CRP for predicting severe and critical COVID-19 patients.

Figure 7.

ROC curve for diagnosis of severe and critical patients with COVID-19. Univariate logistic regression analysis was used to identify the critical patients from moderate, severe COVID-19 patients and controls. Performance of ROC curves of TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10 and CRP for predicting critical COVID-19 patients.