Open Access

SHORT REVIEW

Interleukin-6 and severe COVID-19: a systematic review and meta-analysis

Helia Mojtabavi^1,2, Amene Saghazadeh^1,2, Nima Rezaei^2,3,4

1 Universal Scientific Education and Research Network (USERN), Systematic Review and Meta-Analysis Expert Group (SRMEG), Tehran, Iran
2 Tehran University of Medical Sciences, Children’s Medical Center, Research Center for Immunodeficiencies, Tehran, Iran
3 Tehran University of Medical Sciences, School of Medicine, Department of Immunology, Tehran, Iran
4 Universal Scientific Education and Research Network (USERN), Network of Immunity in Infection, Malignancy and Autoimmunity (NIIMA), Tehran, Iran

* Corresponding Authors: Nima Rezaei, ;

European Cytokine Network 2020, 31(2), 44-49. https://doi.org/10.1684/ecn.2020.0448

Accepted 04 May 2020;

Abstract

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 non-severe 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.

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Keywords

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