Use of siltuximab in patients with COVID-19 pneumonia requiring ventilatory support

Gritti, G.; Raimondi, F.; Ripamonti, D.; Riva, I.; Landi, F.; Alborghetti, L.; Frigeni, M.; Damiani, M.; Mico, C.; Fagiuoli, S.; Cosentini, R.; Luca Lorini, F.; Fabretti, F.; Morgan, J.; Owens, B. M. J.; Kanhai, K.; Cowburn, J.; Rizzi, M.; Di Marco, F.; Rambaldi, A.

COVID-19 is caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SAR-CoV-2), resulting in symptoms, such as fever, cough, and shortness of breath. The SARS-CoV-2 virus has also been suggested to initiate a cytokine storm in patients with COVID-19 evidenced by elevated cytokines, such as interleukin-6 (IL-6) and C-reactive protein (CRP). We report preliminary data from 21 patients with COVID-19 who developed pneumonia/acute respiratory distress syndrome (ARDS) and participated in a compassionate-use program at Papa Giovanni XXIII hospital in Bergamo, Italy. All 21 patients received intravenous siltuximab, a chimeric mAb that binds to and blocks the effect of IL-6, at a dose ranging between 700 to 1,200 mg (median 900 mg). The median age of patients treated was 64 years, and all patients were followed for a median of eight days. Serum CRP levels reduced in all 16 patients with available data following treatment. An improvement in the clinical condition was observed in 33% (7/21) of patients, 43% (9/21) of patients stabilized as evidenced by no clinically relevant change in their condition, and 24% (5/21) experienced a worsening in their condition. Of those patients who experienced a worsening in their condition, one patient died, and one patient experienced a cerebrovascular event. This analysis is presented to inform the medical community of the potential role of siltuximab in treating patients with ARDS secondary to SARS-CoV-2 infection, and a cohort study with patients treated with standard therapy in our hospital is ongoing, and will report the 30-day mortality rates upon completion.