Okur H K, Yalcin K, Tastan C, Demir S, Yurtsever B, Karakus G S, Kancagi D D, Abanuz S, Seyis U, Zengin R, Hemsinlioglu C, Kara M, Yildiz M E, Deliceo E, Birgen N, Pelit N B, Cuhadaroglu C, Kocagoz A S, Ovali E
Acibadem Altunizade Hospital, Chest Disease Unit, Istanbul, Turkey.
Acibadem Labcell Cellular Therapy Laboratory, Istanbul, Turkey.
New Microbes New Infect. 2020 Sep;37:100756. doi: 10.1016/j.nmni.2020.100756. Epub 2020 Sep 7.
Dornase alfa, the recombinant form of the human DNase I enzyme, breaks down neutrophil extracellular traps (NET) that include a vast amount of DNA fragments, histones, microbicidal proteins and oxidant enzymes released from necrotic neutrophils in the highly viscous mucus of cystic fibrosis patients. Dornase alfa has been used for decades in patients with cystic fibrosis to reduce the viscoelasticity of respiratory tract secretions, to decrease the severity of respiratory tract infections, and to improve lung function. Previous studies have linked abnormal NET formations to lung diseases, especially to acute respiratory distress syndrome (ARDS). It is well known that novel coronavirus disease 2019 (COVID-19) pneumonia progresses to ARDS and even multiple organ failure. High blood neutrophil levels are an early indicator of COVID-19 and predict severe respiratory diseases. Also it is reported that mucus structure in COVID-19 is very similar to that in cystic fibrosis due to the accumulation of excessive NET in the lungs. In this study, we showed the recovery of three individuals with COVID-19 after including dornase alfa in their treatment. We followed clinical improvement in the radiological analysis (two of three cases), oxygen saturation (Spo), respiratory rate, disappearance of dyspnoea, coughing and a decrease in NET formation and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load after the treatment. Also here, we share our preliminary results suggesting that dornase alfa has an anti-viral effect against SARS-CoV-2 infection in a green monkey kidney cell line, Vero, and a bovine kidney cell line, MDBK, without determined cytotoxicity on healthy peripheral blood mononuclear cells.
重组人脱氧核糖核酸酶I（DNase I）即度洛西丁，可分解中性粒细胞胞外诱捕网（NET），这些诱捕网包含大量DNA片段、组蛋白、杀菌蛋白和氧化酶，它们由囊性纤维化患者高粘性黏液中坏死的中性粒细胞释放。几十年来，度洛西丁一直用于治疗囊性纤维化患者，以降低呼吸道分泌物的粘弹性，减轻呼吸道感染的严重程度，并改善肺功能。先前的研究已将异常的NET形成与肺部疾病联系起来，尤其是与急性呼吸窘迫综合征（ARDS）相关。众所周知，2019年新型冠状病毒病（COVID-19）肺炎会发展为ARDS，甚至多器官功能衰竭。高血中性粒细胞水平是COVID-19的早期指标，并可预测严重的呼吸道疾病。另据报道，由于肺部NET过度积累，COVID-19中的黏液结构与囊性纤维化中的非常相似。在本研究中，我们展示了三名COVID-19患者在治疗中加入度洛西丁后的康复情况。我们跟踪了治疗后放射学分析（三例中的两例）、血氧饱和度（Spo）、呼吸频率、呼吸困难消失、咳嗽以及NET形成减少和严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒载量降低等临床改善情况。此外，我们在此分享初步结果，表明度洛西丁在绿色猴肾细胞系Vero和牛肾细胞系MDBK中对SARS-CoV-2感染具有抗病毒作用，且对健康外周血单个核细胞无明显细胞毒性。
