一项关于IL-7用于新冠重症患者的随机、双盲、安慰剂对照试验。
A randomized, double-blind, placebo-controlled trial of IL-7 in critically ill patients with COVID-19.
作者信息
Shankar-Hari Manu, Francois Bruno, Remy Kenneth E, Gutierrez Cristina, Pastores Stephen, Daix Thomas, Jeannet Robin, Blood Jane, Walton Andrew H, Salomao Reinaldo, Auzinger Georg, Striker David, Martin Robert S, Anand Nitin J, Bosanquet James, Blood Teresa, Brakenridge Scott, Moldawer Lyle L, Vachharajani Vidula, Yee Cassian, Dal-Pizzol Felipe, Morre Michel, Berbille Frederique, van den Brink Marcel, Hotchkiss Richard
机构信息
Department of Translational Critical Care Medicine, Centre for Inflammation Research, Institute for Regeneration and Repair, The University of Edinburgh, Scotland, United Kingdom.
Medical-Surgical ICU & Inserm CIC 1435 Centre Hospitalier Universitaire, Limoges, France.
出版信息
JCI Insight. 2025 Feb 4;10(6):e189150. doi: 10.1172/jci.insight.189150.
BACKGROUND
Lymphopenia and failure of lymphocytes to mount an early IFN-γ response correlate with increased mortality in COVID-19. Given the essential role of CD4 helper and CD8 cytotoxic cells in eliminating viral pathogens, this profound loss in lymphocytes may impair patients' ability to eliminate the virus. IL-7 is a pleiotropic cytokine that is obligatory for lymphocyte survival and optimal function.
METHODS
We conducted a prospective, double-blind, randomized, placebo-controlled trial of CYT107, recombinant human IL-7, in 109 critically ill, patients with lymphopenia who have COVID-19. The primary endpoint was to assess CYT107's effect on lymphocyte recovery with secondary clinical endpoints including safety, ICU and hospital length-of-stay, incidence of secondary infections, and mortality.
RESULTS
CYT107 was well tolerated without precipitating a cytokine storm or worsening pulmonary function. Absolute lymphocyte counts increased in both groups without a significant difference between CYT107 and placebo. Patients with COVID-19 receiving CYT107 but not concomitant antiviral medications, known inducers of lymphopenia, had a final lymphocyte count that was 43% greater than placebo (P = 0.067). There were significantly fewer treatment-emergent adverse events in CYT107 versus placebo-treated patients (P < 0.001), consistent with a beneficial drug effect. Importantly, CYT107-treated patients had 44% fewer hospital-acquired infections versus placebo-treated patients (P = 0.014).
CONCLUSION
Given that hospital-acquired infections are responsible for a large percentage of COVID-19 deaths, this effect of CYT107 to decrease nosocomial infections could substantially reduce late morbidity and mortality in this highly lethal disease. The strong safety profile of CYT107 and its excellent tolerability provide support for trials of CYT107 in other potential pandemic respiratory viral infections.
TRIAL REGISTRATION
NCT04379076, NCT04426201, NCT04442178, NCT04407689, NCT04927169.
FUNDING
Funding for the trial was provided by RevImmune and the Cancer Research Institute.
背景
淋巴细胞减少以及淋巴细胞无法产生早期干扰素-γ反应与COVID-19患者死亡率增加相关。鉴于CD4辅助细胞和CD8细胞毒性细胞在清除病毒病原体中的重要作用，淋巴细胞的这种严重减少可能会损害患者清除病毒的能力。白细胞介素-7（IL-7）是一种多效性细胞因子，对淋巴细胞的存活和最佳功能至关重要。
方法
我们对109例患有COVID-19的重症淋巴细胞减少患者进行了一项关于重组人IL-7（CYT107）的前瞻性、双盲、随机、安慰剂对照试验。主要终点是评估CYT107对淋巴细胞恢复的影响，次要临床终点包括安全性、重症监护病房（ICU）和住院时间、继发感染发生率和死亡率。
结果
CYT107耐受性良好，未引发细胞因子风暴或使肺功能恶化。两组的绝对淋巴细胞计数均增加，CYT107组与安慰剂组之间无显著差异。接受CYT107但未同时使用已知会导致淋巴细胞减少的抗病毒药物的COVID-19患者，其最终淋巴细胞计数比安慰剂组高43%（P = 0.067）。与安慰剂治疗的患者相比，CYT107治疗的患者出现的治疗突发不良事件明显更少（P < 0.001），这与药物的有益作用一致。重要的是，与安慰剂治疗的患者相比，接受CYT107治疗的患者医院获得性感染减少了44%（P = 0.014）。
结论
鉴于医院获得性感染在很大比例的COVID-19死亡病例中起作用，CYT107降低医院感染的这种作用可能会大幅降低这种高致死性疾病的晚期发病率和死亡率。CYT107强大的安全性及其出色的耐受性为在其他潜在的大流行性呼吸道病毒感染中进行CYT107试验提供了支持。
试验注册
NCT04379076、NCT04426201、NCT04442178、NCT04407689、NCT04927169。
资助
该试验的资金由RevImmune和癌症研究所提供。
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