Associations between Serum Interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10) and Disease Severity of COVID-19: A Systematic Review and Meta-Analysis

BACKGROUND: To investigate the association between interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10) and the disease severity of coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: We systematically searched records investigating the role of interleukins (IL-1β, IL-2, IL-4, IL-6, IL-8, and IL-10) in COVID-19 patients in Web of Science, Pubmed, and Embase through December 2020. Data were extracted and pooled, and the weighted mean difference (WMD) and its 95% confidence interval (CI) were calculated. The funnel plot and the nonparametric trim and fill method were used to visualize and adjust the publication bias. RESULTS: In total, 61 studies enrolled 14,136 subjects (14,041 patients and 95 healthy subjects) were enrolled in this meta-analysis. Our results showed that serum IL-2, IL-4, IL-6, and IL-10 levels were elevated in COVID-19 patients compared to healthy controls, and IL-6, IL-8, and IL-10 levels were increased in severe COVID-19 cases compared to nonsevere patients. Additionally, the levels of IL-1β, IL-6, and IL-8 were elevated in nonsurvivor patients compared to survivors. For patients in the intensive care unit (ICU), IL-6 and IL-8 levels were increased than that in non-ICU patients. CONCLUSIONS: Elevated levels of IL-6, IL-8, and IL-10 were associated with the disease severity of COVID-19, and elevated levels of IL-1β, IL-6, and IL-8 were related to the prognosis of COVID-19 patients, which could be used to evaluate COVID-19 patients' disease severity and prognosis.