Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, Northwell Health, 300 Community Drive, Manhasset, NY, 11030, USA.
Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington and the Center for Immunity and Immunotherapies, Seattle Children's Research Institute, 1900 9th Ave, Seattle, WA, 98101, USA.
Mol Med. 2020 Sep 29;26(1):91. doi: 10.1186/s10020-020-00215-w.
Mechanically ventilated patients with COVID-19 have a mortality of 24-53%, in part due to distal mucopurulent secretions interfering with ventilation. DNA from neutrophil extracellular traps (NETs) contribute to the viscosity of mucopurulent secretions and NETs are found in the serum of COVID-19 patients. Dornase alfa is recombinant human DNase 1 and is used to digest DNA in mucoid sputum. Here, we report a single-center case series where dornase alfa was co-administered with albuterol through an in-line nebulizer system.
Demographic and clinical data were collected from the electronic medical records of five mechanically ventilated patients with COVID-19-including three requiring veno-venous extracorporeal membrane oxygenation-treated with nebulized in-line endotracheal dornase alfa and albuterol, between March 31 and April 24, 2020. Data on tolerability and response were analyzed.
The fraction of inspired oxygen requirements was reduced for all five patients after initiating dornase alfa administration. All patients were successfully extubated, discharged from hospital and remain alive. No drug-associated toxicities were identified.
Results suggest that dornase alfa will be well-tolerated by patients with severe COVID-19. Clinical trials are required to formally test the dosing, safety, and efficacy of dornase alfa in COVID-19, and several have been recently registered.
COVID-19 机械通气患者的死亡率为 24-53%，部分原因是远端黏液脓性分泌物干扰通气。中性粒细胞胞外陷阱（NETs）的 DNA 有助于黏液脓性分泌物的粘性，并且 COVID-19 患者的血清中存在 NETs。Dornase alfa 是重组人 DNAse 1，用于消化黏液中的 DNA。在这里，我们报告了一项单中心病例系列研究，其中 dornase alfa 与沙丁胺醇通过在线雾化器系统联合使用。
从 2020 年 3 月 31 日至 4 月 24 日期间，通过在线气管内 dornase alfa 和沙丁胺醇雾化器系统治疗的五例 COVID-19 机械通气患者的电子病历中收集了人口统计学和临床数据，包括三名需要静脉-静脉体外膜肺氧合的患者。分析了可耐受性和反应数据。
所有五例患者在开始使用 dornase alfa 后，吸入氧气的分数要求降低。所有患者均成功拔管，出院并存活。未发现与药物相关的毒性。
结果表明，dornase alfa 将被 COVID-19 严重患者耐受良好。需要进行临床试验来正式测试 dornase alfa 在 COVID-19 中的剂量、安全性和疗效，最近已经注册了几项临床试验。
