Aguareles José, Forné Carles, García-Casas Ana, Santamaría-Corral Guillermo, Carnevali-Ruiz Daniel, Sotres-Fernández Gabriel, Solera Javier T, Guisado-Vasco Pablo
Internal Medicine Department, Hospital Universitario Quirónsalud Madrid, Madrid, Spain.
Department of Medicine, Faculty of Medicine, Health and Sports, European University of Madrid, Madrid, Spain.
BMC Infect Dis. 2025 May 8;25(1):676. doi: 10.1186/s12879-025-11001-6.
Our aim in this work is to find biomarkers to optimize therapy with IL-6 inhibitors, as not all clinical trials have shown clear benefits on mortality or mechanical ventilation progression. Given the link between delayed seroconversion and higher complication risks, we aim to test if evaluating SARS-CoV-2 spike protein antibody status before treatment could enhance IL-6 inhibitor therapy effectiveness in COVID-19 patients.
We conducted a post hoc analysis of the COVACTA study, a phase 3, randomized, double-blind, placebo-controlled trial of the efficacy and safety of tocilizumab in hospitalized patients with severe COVID-19. Cox and logistic regression analysis were used to assess the tocilizumab's efficacy in severe COVID-19 patients on survival and ICU stay at day 28, based on SARS-CoV-2 S-spike and neutralizing antibody levels.
Tocilizumab reduced 28-day mortality over placebo in patients with low S-spike antibody titers (20% vs. 29%). No benefit was observed for higher antibody levels. Patients with low S-spike antibody levels treated with tocilizumab exhibited a lower probability of ICU stay at day 28 compared to those treated with placebo (63% vs. 82%). No significant differences were noted in mortality and ICU stay based on whole neutralizing antibody titers.
Our findings suggest that using IL-6 inhibitors in severe COVID-19 patients with low S-spike antibody titers may improve clinical outcomes.
Not applicable.
我们这项研究的目的是寻找生物标志物，以优化白细胞介素-6抑制剂的治疗，因为并非所有临床试验都显示出对死亡率或机械通气进展有明显益处。鉴于血清学转换延迟与更高的并发症风险之间存在关联，我们旨在测试在治疗前评估严重急性呼吸综合征冠状病毒2（SARS-CoV-2）刺突蛋白抗体状态是否能提高白细胞介素-6抑制剂对2019冠状病毒病（COVID-19）患者的治疗效果。
我们对COVACTA研究进行了事后分析，这是一项关于托珠单抗治疗重症COVID-19住院患者疗效和安全性的3期随机双盲安慰剂对照试验。基于SARS-CoV-2 S刺突蛋白和中和抗体水平，采用Cox回归分析和逻辑回归分析评估托珠单抗对重症COVID-19患者第28天生存和入住重症监护病房（ICU）情况的疗效。
在S刺突蛋白抗体滴度较低的患者中，托珠单抗降低了28天死亡率（20%对29%）。抗体水平较高时未观察到益处。与接受安慰剂治疗的患者相比，接受托珠单抗治疗的S刺突蛋白抗体水平较低的患者在第28天入住ICU的可能性较低（63%对82%）。基于整体中和抗体滴度的死亡率和入住ICU情况未发现显著差异。
我们的研究结果表明，在S刺突蛋白抗体滴度较低的重症COVID-19患者中使用白细胞介素-6抑制剂可能改善临床结局。
不适用。
