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.

Integration of heparin-binding protein and interleukin-6 in the early prediction of respiratory failure and mortality in pneumonia by SARS-CoV-2 (COVID-19)

“…Another survey in only 40 patients split into those requiring MV and admission in an intensive care unit (n=20) and into those with stable diseases showed similar increase of IL-6 among the most severe cases [13]. This was also the nding of a cohort comparing 17 patients with critical COVID-19 to 85 patients with mild or moderate disease [14]. The present study goes well beyond previous prospective cohorts since it demonstrates the importance of admission levels for the early prediction of the disease course.…”

Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

“…While the number of animals enrolled in this study was not sufficient to look at species-specific differences and their effect on disease progression, we found that a higher ratio of IL-6:IL-10 cytokine in plasma was associated with disease severity. Undoubtedly, more studies are needed to prove or disprove the single contribution of IL-10 and IL-6 in the outcome of COVID-19 disease and to identify the source of these two potential key players 48 . Overall, this study uncovers critical steps in the immune events of the host response to SARS- Table 1).…”

Broncho-alveolar inflammation in COVID-19 patients: a correlation with clinical outcome

“…Moreover, authors have demonstrated a direct correlation with IL6 serum levels, suggesting that both cytokines could be used as predictors of higher risk of disease deterioration [20]. Thus, despite its well-known antiin ammatory role, an exaggerated release of IL10, together with other pro-in ammatory factors from activated macrophages is integrated in the context of the cytokine storm and considered a marker of disease severity [21]. In the present study, however, there was no signi cant variation in IL10 BAL levels either in relation to disease severity or according to survival (Fig.…”