Interleukin-6 in Covid-19: A systematic review and meta-analysis

Abstract

Coronaviruses may activate dysregulated host immune responses. As exploratory studies have suggested that interleukin-6 (IL-6) levels are elevated in cases of complicated Covid-19, we undertook a systematic review and meta-analysis to assess the evidence in this field. We systematically searched MEDLINE and EMBASE for studies investigating the immunological response in Covid-19; additional grey literature searches were undertaken. Study selection and data abstraction was undertaken independently by two authors. Meta-analysis was undertaken using random effects models to compute ratios of means with 95% confidence intervals (95%CIs). Eight published studies and two preprints (n = 1798) were eligible for inclusion. Meta-analysis of mean IL-6 concentrations demonstrated 2.9-fold higher levels in patients with complicated Covid-19 compared with patients with noncomplicated disease (six studies; n = 1302; 95%CI, 1.17-7.19; I² = 100%). Consistent results were found in sensitivity analyses exclusively restricted to studies comparing patients requiring ICU admission vs no ICU admission (two studies; n = 540; ratio of means = 3.24; 95%CI, 2.54-4.14; P < .001; I² = 87%). Nine of ten studies were assessed to have at least moderate risk of bias. In patients with Covid-19, IL-6 levels are significantly elevated and associated with adverse clinical outcomes. Inhibition of IL-6 may be a novel target for therapeutics for the management of dysregulated host responses in patients with Covid-19 and high-quality studies of intervention in this field are urgently required.

Keywords: Covid-19; IL6; SARS-CoV-2; Tocilizumab; cytokine storm; interleukin.

FIGURE 1

Study selection flow

FIGURE 2

Meta‐analysis of serum IL‐6 levels in COVID‐19. A, Patients with complicated COVID‐19 vs noncomplicated; B, Patients requiring ICU admission vs not requiring ICU admission; C, Patients with severe or critical COVID‐19 vs mild COVID‐19