Yessayan Lenar T, Neyra Javier A, Westover Angela J, Szamosfalvi Balazs, Humes H David
Department of Internal Medicine (Nephrology), University of Michigan, Ann Arbor, MI.
Department of Internal Medicine (Nephrology, Bone and Mineral Metabolism), University of Kentucky, Lexington, KY.
Crit Care Explor. 2022 May 19;4(5):e0694. doi: 10.1097/CCE.0000000000000694. eCollection 2022 May.
To evaluate safety and clinical outcomes of extracorporeal immunomodulation treatment with a selective cytopheretic device (SCD) in COVID-19 ICU patients with multiple organ failure.
Two-center, prospective, single-arm treatment clinical trial.
ICUs at two academic medical centers between September 2020 and July 2021.
Twenty-two COVID-10 patients in the ICU with acute respiratory distress syndrome who required mechanical ventilation. Nearly all included patients in the intervention group except one had acute kidney injury requiring continuous renal replacement therapy (CRRT). Sixteen subjects meeting enrollment criteria were selected as contemporaneous controls from a concurrent prospective registry CRRT trial.
Treatment with an SCD integrated into a continuous renal replacement extracorporeal blood circuit for up to 10 days to provide autologous leukocyte cell processing to immunomodulate the hyperinflammatory disease state of COVID-19.
SCD treatment in COVID-19 ICU patients with multiple organ failure demonstrated an acceptable safety profile with no device-related serious adverse events. Treatment of these patients resulted in the selective removal of highly activated circulating leukocytes as determined by flow cytometry. Significant reductions were observed in the elevated plasma levels of eight cytokines and biomarkers, including interleukin (IL)6, IL15, IL10, and soluble ST2, which are predictive of mortality in COVID-19 patients. Significant improvements of leukocytosis and Po/Fio ratios occurred during treatment not observed in the control group. SCD-treated subjects had a reduction in 60-day mortality of 50% compared with 81% in the control cohort. The subjects who received greater than 96 hours of SCD treatment, per protocol, had a further reduction in mortality to 31% ( < 0.012).
Extracorporeal immunomodulation therapy with an SCD demonstrated safety without any device-related serious adverse events. As a rescue therapy in COVID-19 ICU patients progressing to multiple organ failure despite maximal pharmacologic and organ support interventions, SCD treatment resulted in improved clinical outcomes. This autologous leukocyte cell processing technology may provide a new approach in the treatment of unremitting hyperinflammation of COVID-19.
评估采用选择性血细胞分离装置（SCD）对多器官功能衰竭的新冠重症监护病房（ICU）患者进行体外免疫调节治疗的安全性和临床结局。
两中心、前瞻性、单臂治疗临床试验。
2020年9月至2021年7月期间两个学术医学中心的ICU。
22例入住ICU的新冠患者，患有急性呼吸窘迫综合征，需要机械通气。干预组中几乎所有纳入患者（除1例）均有急性肾损伤，需要持续肾脏替代治疗（CRRT）。从一项同期前瞻性注册CRRT试验中选取16名符合纳入标准的受试者作为同期对照。
将SCD集成到持续肾脏替代体外血液回路中进行治疗，最长10天，以提供自体白细胞处理，从而对新冠的高炎症疾病状态进行免疫调节。
对多器官功能衰竭的新冠ICU患者进行SCD治疗显示出可接受的安全性，未发生与设备相关的严重不良事件。通过流式细胞术测定，对这些患者的治疗导致高度活化的循环白细胞被选择性清除。观察到包括白细胞介素（IL）6、IL15、IL10和可溶性ST2在内的8种细胞因子和生物标志物的血浆水平显著降低，这些指标可预测新冠患者的死亡率。治疗期间观察到白细胞增多症和氧合指数显著改善，而对照组未观察到。与对照组81%的死亡率相比，接受SCD治疗的受试者60天死亡率降低了50%。按照方案接受SCD治疗超过96小时的受试者死亡率进一步降至31%（P<0.012）。
采用SCD进行体外免疫调节治疗显示出安全性，未发生与设备相关的严重不良事件。作为对尽管接受了最大程度的药物和器官支持干预但仍进展为多器官功能衰竭的新冠ICU患者的一种挽救治疗方法，SCD治疗改善了临床结局。这种自体白细胞处理技术可能为治疗新冠持续高炎症提供一种新方法。
