Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Pharmacol Res. 2020 Jul;157:104866. doi: 10.1016/j.phrs.2020.104866. Epub 2020 May 6.
COVID-19 is a medical emergency, with 20 % of patients presenting with severe clinical manifestations. From the pathogenetic point of view, COVID-19 mimics two other well-known diseases characterized by cytokine storm and hyper-activation of the immune response, with consequent organ damage: acute graft-versus-host disease (aGVHD) and macrophage activation syndrome (MAS). Hematologists are confident with these situations requiring a prompt therapeutic approach for switching off the uncontrolled cytokine release; here, we discuss pros and cons of drugs that are already employed in hematology in the light of their possible application in COVID-19. The most promising drugs might be: Ruxolitinib, a JAK1/2 inhibitor, with a rapid and powerful anti-cytokine effect, tyrosine kinase inhibitors (TKIs), with their good anti-inflammatory properties, and perhaps the anti-Cd26 antibody Begelomab. We also present immunological data from gene expression experiments where TKIs resulted effective anti-inflammatory and pro-immune drugs. A possible combined treatment algorithm for COVID-19 is here proposed.
新型冠状病毒肺炎是一种医学急症，20%的患者表现出严重的临床症状。从发病机制的角度来看，新型冠状病毒肺炎类似于另外两种由细胞因子风暴和免疫反应过度激活引起的、导致器官损伤的知名疾病：急性移植物抗宿主病（aGVHD）和巨噬细胞活化综合征（MAS）。血液科医生对这些需要迅速采取治疗措施以阻断失控的细胞因子释放的情况非常熟悉；在这里，我们根据这些药物在血液学中的可能应用，讨论了已经在血液学中使用的药物的优缺点。最有前途的药物可能有：JAK1/2 抑制剂芦可替尼，具有快速而强大的抗细胞因子作用；酪氨酸激酶抑制剂（TKI），具有良好的抗炎特性；或许还有抗 CD26 抗体贝洛单抗。我们还展示了来自基因表达实验的免疫学数据，其中 TKI 被证明是有效的抗炎和免疫调节药物。本文提出了一种用于新型冠状病毒肺炎的可能联合治疗方案。
