Circulating Level of Interleukin-6 Correlates With Poor Prognosis in Males With COVID-19: A Systematic Review and Meta-Analysis

Abstract

Coronavirus disease 2019 (COVID-2019), caused by severe acute respiratory syndrome coronavirus 2, has become a worldwide epidemic and claimed millions of lives. Accumulating evidence suggests that males suffer more severe symptoms and higher mortality than females, but the underlying mechanism of this sex predisposition remains unclear. We aimed to explore whether inflammatory cytokines are risk factors correlated with this sex predisposition, especially in terms of the severity and mortality of COVID-19 patients. To clarify whether inflammatory cytokines are related to male sex bias towards increased mortality, we systematically searched PubMed, Embase and Web of Science to identify related studies with the keywords "COVID-19" and "cytokines". We preliminarily screened 13468 studies from the databases. A total of 77 articles with 13468 patients were ultimately included in our study. The expression levels of interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-2 receptor (IL-2R) and tumour necrosis factor α (TNF-α) were significantly different between males and females. The serum level of IL-6 was much higher in males than in females, which implies that the increased mortality and severity in males was partly due to the higher level of IL-6. Interestingly, we also found that in the severe and non-survivor groups, European patients had elevated levels of IL-6 compared with Asian patients. These large-scale data demonstrated that the circulating level of IL-6 is a potential risk factor for severity and high mortality in COVID-19. The upregulation of IL-6 may be a driving factor for severity and high mortality in males with COVID-19.Funding Information: This work was financially supported by National Key Research and Development Project of China (2020YFA0708003).Declaration of Interests: There is no conflict of interest.