Abstract
Background: Coronavirus disease 2019 (COVID-2019), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide epidemic and claimed millions of lives. Accumulating evidence suggests that cytokines storms are closely associated to COVID-19 severity and death. Here, we aimed to explore the key factors related to COVID-19 severity and death, especially in terms of the male patients and those in western countries. Methods: To clarify whether inflammatory cytokines have role in COVID-19 severity and death, we systematically searched PubMed, Embase, Cochrane library and Web of Science to identify related studies with the keywords “COVID-19″ and “cytokines”. The data were measured as the mean with 95% confidence interval (CI) by Review Manager 5.3 software. The risk of bias was assessed for each study using appropriate checklists. Results: We preliminarily screened 13,468 studies from the databases. A total of 77 articles with 13,468 patients were ultimately included in our study. The serum levels of cytokines such as interleukin-6 (IL-6), IL-10, interleukin-2 receptor (IL-2R), tumor necrosis factor (TNF)-α, IL-1β, IL-4, IL-8 and IL-17 were higher in the severity or death group. Notably, we also found that the circulating levels of IL-6, IL-10, IL-2R and TNF-α were significantly different between males and females. The serum levels of IL-6, IL-10, IL-2R and TNF-α were 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 these cytokines. Moreover, we found that in the severe and non-survivor groups, European patients had elevated levels of IL-6 compared with Asian patients. Conclusion: These large-scale data demonstrated that the circulating levels of IL-6, IL-10, IL-2R, IL-1β, IL-4, IL-8 and IL-17 are potential risk factors for severity and high mortality in COVID-19. Simultaneously, the upregulation of these cytokines may be driving factors for the sex and region predisposition.
Highlights
Coronavirus disease 2019 (COVID-2019), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised major public health crises since 2019
Seventy-three studies were published in normal journals, and four were published in preprint journals.14 cytokines were reported in these 77 studies, including IL-1β, IL-2, interleukin-2 receptor (IL-2R), IL-4, IL-5, IL-6, IL-8, IL10, IL-15, IL-17, TNF-α, interferon γ (IFN-γ), MCP-1, and CXCL-10
Eight cytokines were included in our meta-analysis, containing IL-1β, IL-2R, IL4, IL-6, IL-8, IL-10, IL-17, and TNF- α
Summary
Coronavirus disease 2019 (COVID-2019), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has raised major public health crises since 2019. Patients with COVID-19 shows a higher risk of mortality in males sex (Griffith et al, 2020). The discrepancy in COVID-19 outcomes between male and female patients may be attributed to several biological and social factors, especially cytokine storms (Griffith et al, 2020). Coronavirus disease 2019 (COVID-2019), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a worldwide epidemic and claimed millions of lives. Accumulating evidence suggests that cytokines storms are closely associated to COVID-19 severity and death. We aimed to explore the key factors related to COVID-19 severity and death, especially in terms of the male patients and those in western countries
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