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. 2020 Oct 2;31(2):44–49. doi: 10.1684/ecn.2020.0448

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

Helia Mojtabavi 1,2, Amene Saghazadeh 1,2, Nima Rezaei 2,3,4,5,✉
PMCID: PMC7530350  PMID: 32933891

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 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.

Key words: age, COVID-19, severity, inflammation, interleukin-6, meta-analysis

Footnotes

Acknowledgments and disclosures

Ethics approval and consent to participate: not applicable. Consent for publication: not applicable. Availability of data and materials: not applicable. Conflicts of interests: the authors declare that they have no competing interests. Funding: there is no funding for the present study. Authors’ contributions: H.M. conceptualized the study, conducted database search, search results screening, detailed review, data extraction, quality assessment, and prepared the initial draft. A.S. prepared the final draft. N.R. supervised the project and critically appraised the manuscript. Acknowledgments: not applicable.

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