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

Coomes, Eric A.; Haghbayan, Hourmazd

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; I (2) = 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; I (2) = 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.