Giudice Valentina, Pagliano Pasquale, Vatrella Alessandro, Masullo Alfonso, Poto Sergio, Polverino Benedetto Maria, Gammaldi Renato, Maglio Angelantonio, Sellitto Carmine, Vitale Carolina, Serio Bianca, Cuffa Bianca, Borrelli Anna, Vecchione Carmine, Filippelli Amelia, Selleri Carmine
Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana" University of Salerno, Baronissi, Italy.
Clinical Pharmacology Unit, University Hospital "San Giovanni di Dio e Ruggi d'Aragona", Salerno, Italy.
Front Pharmacol. 2020 Jun 5;11:857. doi: 10.3389/fphar.2020.00857. eCollection 2020.
To date, there are no specific therapeutic strategies for treatment of COVID-19. Based on the hypothesis that complement and coagulation cascades are activated by viral infection, and might trigger an acute respiratory distress syndrome (ARDS), we report clinical outcomes of 17 consecutive cases of SARS-CoV-2-related ARDS treated (N = 7) with the novel combination of ruxolitinib, a JAK1/2 inhibitor, 10 mg/twice daily for 14 days and eculizumab, an anti-C5a complement monoclonal antibody, 900 mg IV/weekly for a maximum of three weeks, or with the best available therapy (N = 10). Patients treated with the combination showed significant improvements in respiratory symptoms and radiographic pulmonary lesions and decrease in circulating D-dimer levels compared to the best available therapy group. Our results support the use of combined ruxolitinib and eculizumab for treatment of severe SARS-CoV-2-related ARDS by simultaneously turning off abnormal innate and adaptive immune responses.
迄今为止，尚无针对治疗新型冠状病毒肺炎（COVID-19）的特异性治疗策略。基于补体和凝血级联反应被病毒感染激活并可能引发急性呼吸窘迫综合征（ARDS）这一假设，我们报告了17例连续的严重急性呼吸综合征冠状病毒2（SARS-CoV-2）相关ARDS患者的临床结局，其中7例接受了鲁索替尼（一种JAK1/2抑制剂，10毫克/每日两次，共14天）和依库珠单抗（一种抗C5a补体单克隆抗体，900毫克静脉注射/每周一次，最多三周）的新联合治疗，另外10例接受了最佳可用治疗。与最佳可用治疗组相比，接受联合治疗的患者在呼吸症状和胸部影像学肺部病变方面有显著改善，循环D-二聚体水平降低。我们的结果支持联合使用鲁索替尼和依库珠单抗，通过同时抑制异常的固有免疫和适应性免疫反应来治疗严重的SARS-CoV-2相关ARDS。
