Anakinra for patients with COVID-19: an updated systematic review and meta-analysis

Severe COVID-19 patients can develop a maladaptive immune response with hyper-production of cytokines and chemokines which lead to alveolar damage, endothelial activation, coagulopathy and thromboembolic events. We performed a meta-analysis which included any study performed on COVID-19 patients with respiratory hypoxemic failure who received anakinra versus any comparator. Primary endpoint was mortality. Secondary endpoints were intubation rate, superinfection and thromboembolic events. Subgroups analyses included patients in general ward, with hyperinflammation and/or baseline ratio of arterial oxygen partial pressure (PaO2) to fractional inspired oxygen (FiO2) >200. Twenty-four studies were included. Mortality in anakinra patients was significantly lower than mortality of controls (19% vs. 28%; p < 0.0001). Anakinra patients had significantly lower risk of intubation (16% vs. 33%; p < 0.001). Mortality reduction was confirmed in general ward settings, in patients with hyperinflammation and with PaO2/FiO2 >200, but not when selecting randomized studies only. A trend towards increased mortality in more severe patients was observed.