Associations between Interleukin-4 and COVID-19 severity: A systematic review and meta-analysis

ABSTRACT

Introduction: This systematic review and meta-analysis aimed to determine the correlation between IL-4 concentrations and COVID-19 severity. Methods: This study was designed as a systematic review and meta-analysis and was performed in accordance to the PRISMA statement. Titles, abstracts, and full texts of articles were independently reviewed by at least 2 authors. Continuous variables were compared by the mean difference (MD) with 95% confidence interval (CI). Results: Thirty-three studies reported IL-4 levels among severe versus non-severe COVID-19 patients. Pooled analysis showed that levels of IL-4 among those groups varied and amounted to 2.72 ± 3.76 pg/mL vs 3.08 ± 4.14 pg/mL (MD =-0.26;95%CI-0.43 to-0.10;p = 0.002. In addition, eight studies reported levels of IL-4 among COVID-19 patients who survived vs deceased and was 2.61 ± 0.49 pg/mL vs (3.44 ± 16.4 pg/mL, respectively (MD = 0.22;95%CI 0.08 to 0.37;p = 0.002). Discussion: This detailed systematic review and meta-analysis revealed that the plasma concentration of IL-4 is a potential risk factor for COVID-19 severity and mortality. Specifically, old age and male gender were associated with high IL-4 levels. Lung damage could result from the change in IL-4 concentration, thus making critical and severe COVID-19 cases at a very high risk of dying, thereby reducing their quality of life. Therefore, strategies such as using monoclonal antibodies to inhibit Th2 cytokines could be explored in developing an effective treatment regimen for COVID-19 patients. Take-home message An independent risk factor for the severity and fatality of COVID-19 is the plasma levels of IL-4. High IL-4 levels are specifically related to old age and male gender. Lung damage may be a result of the change in IL-4 concentration, placing COVID-19 critically and severely ill at a high risk of dying. © 2022 by the authors.