Conclusion In summary, in these severe and critically ill patients, itolizumab was able to reduce IL-6 concentrations. Notably, itolizumab-related adverse events were not reported. Patients with baseline IL-6 levels below 200 pg/ml, showed prompt clinical and radiological recovery. We anticipate that the timely use of this anti-inflammatory antibody in combination with the appropriate antiviral and anticoagulant therapy could reduce the mortality associated with COVID-19. The analysis of the complete-series will be published shortly. Summary points Inflammatory cytokine-release syndrome is associated with the progression of the coronavirus disease (COVID-19). No current therapy has proven effective for the management of this syndrome so far. Itolizumab is a humanized monoclonal antibody that recognizes human CD6 and its effect is associated with the reduction of pro-inflammatory cytokines release. We present three COVID-19 cases who developed severe respiratory distress together with multifocal interstitial pneumonia. The patients were treated with itolizumab combined with antiviral therapies. Itolizumab reduced circulating IL-6 concentrations in the three COVID-19 patients. Two patients showed rapid ventilatory and radiological improvement and were fully recovered. Itolizumab-related adverse events were not reported. These cases show that the timely use of this anti-inflammatory antibody in combination with the appropriate antiviral and anticoagulant therapy could reduce the mortality associated with COVID-19.