Background

Evidence links COVID-19 severity to hyper-inflammation. Treatment with tocilizumab, a monoclonal antibody directed against the interleukin-6 (IL-6) receptor, was shown to lead to clinical improvement in patients with severe COVID-19. We, therefore, performed the present systematic review and meta-analysis to investigate whether the circulating levels of IL-6 is a reliable indicator of disease severity among patients affected with COVID-19.

Methods

A systematic search was conducted in PubMed, Scopus, Web of Science, and Google Scholar on April 19, 2020.

Results

Eleven studies provided data of IL-6 levels in patients with severe to critical COVID-19 (severe) and patients with mild to moderate COVID-19 (non-severe). The included studies were of moderate to high quality. The mean patients’ age was 60.9 years, ranging from 45.2 to 76.7 years in the severe group and 46.8 years, ranging from 37.9 to 61 years, in the nonsevere group. Fifty-two percent were male in the severe group, as compared to 46% in the non-severe group. An overall random effects meta-analysis showed significantly higher serum levels of IL-6 in the severe group than in the non-severe group with a mean difference of +23.1 pg/mL (95% CI: 12.42–33.79) and the overall effect of 4.24 (P-value < 0.001). Meta-regressions showed that neither age nor sex significantly influenced the mean difference of IL-6 between the groups.

Conclusions

Meta-analysis and meta-regression reveal a reliable relationship between IL-6 and COVID-19 severity, independent of age and sex. Future research is, however, required to assess the effect of BMI on the pattern of IL-6 production in patients with COVID-19. Also, there might be confounding factors that influence the relationship between IL-6 and COVID-19 severity and remain as yet unknown.

中文翻译：

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白细胞介素6和严重COVID-19：系统评价和荟萃分析。

背景

证据将COVID-19的严重程度与过度炎症联系在一起。研究表明，针对严重白介素6（IL-6）受体的单克隆抗体托珠单抗治疗可导致临床改善。因此，我们进行了系统的综述和荟萃分析，以调查IL-6的循环水平是否是受COVID-19影响的患者中疾病严重程度的可靠指标。

方法

2020年4月19日，在PubMed，Scopus，Web of Science和Google Scholar中进行了系统的搜索。

结果

十一项研究提供了重度至严重COVID-19（严重）和轻度至中度COVID-19（非严重）患者的IL-6水平数据。纳入的研究为中等至高质量。重度组患者的平均年龄为60.9岁，重度组为45.2至76.7岁，非重度组为46.8岁，为37.9至61岁。严重组中男性占52％，而非严重组中男性占46％。总体随机荟萃分析显示，严重组的血清IL-6水平显着高于非严重组，平均差异为+23.1 pg / mL（95％CI：12.42–33.79）。的4.24（P-值<0.001）。荟萃回归显示，年龄和性别均未显着影响两组间IL-6的平均差异。

结论

荟萃分析和荟萃回归显示IL-6和COVID-19严重性之间存在可靠的关系，而与年龄和性别无关。但是，需要进一步的研究来评估BMI对COVID-19患者IL-6产生模式的影响。同样，可能存在影响IL-6与COVID-19严重性之间关系的混淆因素，并且仍然未知。