PDF(Pubmed)
Abstract：
BACKGROUND: Post-COVID-19 Syndrome (PCS) includes neurological manifestations, especially fatigue and cognitive deficits. Immune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation are discussed as potential pathophysiological mechanisms. The post-corona-virus immune treatment (PoCoVIT) trial is a phase 2a randomized, controlled, double-blind trial designed to evaluate the effect of methylprednisolone versus placebo on cognitive impairment in PCS. This trial is designed based on the hypothesised autoimmunological pathogenesis and positive aberrations, employing a series of off-label applications.
METHODS: Recruitment criteria include a diagnosis of PCS, a minimum age of 18 years and self-reported cognitive deficits at screening. A total of 418 participants will be randomly assigned to either verum or placebo intervention in the first phase of the trial. The trial will consist of a first trial phase intervention with methylprednisolone versus placebo for six weeks, followed by a six-week treatment interruption period. Subsequently, an open second phase will offer methylprednisolone to all participants for six weeks. Outpatient follow-up visits will take place two weeks after each trial medication cessation. The third and final follow-up, at week 52, will be conducted through a telephone interview. The primary outcome measures an intra-patient change of 15 or more points in the memory satisfaction subscale of the Multifactorial Memory Questionnaire (MMQ) from baseline to follow-up 1 (week 8). Key secondary outcomes include long-term intra-patient changes in memory satisfaction from baseline to follow-up 2 (week 20), changes in other MMQ subscales (follow-up 1 and 2), and changes in neuropsychological and cognitive scores, along with assessments through questionnaires focusing on quality of life, fatigue, and mood over the same periods. Exploratory outcomes involve molecular biomarkers variations in serum and cerebrospinal fluid, as well as structural and functional brain magnetic resonance imaging (MRI) parameters changes related to cognition.
CONCLUSIONS: This trial aims to contribute novel evidence for treating patients with PCS, with a primary focus on those manifesting cognitive deficits. By doing so, it may enhance comprehension of the underlying pathophysiological mechanisms, thereby facilitating biomarker research to advance our understanding and treatment of patients with PCS.
METHODS: Recruitment criteria include a diagnosis of PCS, a minimum age of 18 years and self-reported cognitive deficits at screening. A total of 418 participants will be randomly assigned to either verum or placebo intervention in the first phase of the trial. The trial will consist of a first trial phase intervention with methylprednisolone versus placebo for six weeks, followed by a six-week treatment interruption period. Subsequently, an open second phase will offer methylprednisolone to all participants for six weeks. Outpatient follow-up visits will take place two weeks after each trial medication cessation. The third and final follow-up, at week 52, will be conducted through a telephone interview. The primary outcome measures an intra-patient change of 15 or more points in the memory satisfaction subscale of the Multifactorial Memory Questionnaire (MMQ) from baseline to follow-up 1 (week 8). Key secondary outcomes include long-term intra-patient changes in memory satisfaction from baseline to follow-up 2 (week 20), changes in other MMQ subscales (follow-up 1 and 2), and changes in neuropsychological and cognitive scores, along with assessments through questionnaires focusing on quality of life, fatigue, and mood over the same periods. Exploratory outcomes involve molecular biomarkers variations in serum and cerebrospinal fluid, as well as structural and functional brain magnetic resonance imaging (MRI) parameters changes related to cognition.
CONCLUSIONS: This trial aims to contribute novel evidence for treating patients with PCS, with a primary focus on those manifesting cognitive deficits. By doing so, it may enhance comprehension of the underlying pathophysiological mechanisms, thereby facilitating biomarker research to advance our understanding and treatment of patients with PCS.
摘要：
背景：COVID-19后综合征（PCS）包括神经系统表现，尤其是疲劳和认知缺陷。免疫失调,自身免疫,内皮功能障碍,病毒持久性，和病毒再激活被讨论为潜在的病理生理机制。电晕后病毒免疫治疗（PoCoVIT）试验是第2a期随机，控制,旨在评估甲基强的松龙与安慰剂对PCS认知障碍的影响的双盲试验。本试验是基于假设的自身免疫发病机制和阳性畸变设计的，采用一系列标签外应用程序。
方法：招募标准包括对PCS的诊断，最小年龄为18岁，筛查时自我报告的认知障碍。在试验的第一阶段，总共418名参与者将被随机分配到verum或安慰剂干预。该试验将包括甲基强的松龙与安慰剂的第一阶段干预，为期六周，随后是6周的治疗中断期。随后，开放的第二阶段将为所有参与者提供甲基强的松龙，为期六周。门诊随访将在每次试验药物停止后两周进行。第三次也是最后一次后续行动，在第52周，将通过电话进行采访。主要结果测量了从基线到随访1（第8周）的多因素记忆问卷（MMQ）的记忆满意度子量表中15个或更多个点的患者内部变化。关键的次要结果包括从基线到随访2（第20周）的患者内记忆满意度的长期变化，其他MMQ分量表的变化(随访1和2)，以及神经心理学和认知评分的变化，以及通过关注生活质量的问卷进行的评估，疲劳,和情绪在同一时期。探索性结果涉及血清和脑脊液中的分子生物标志物变异，以及与认知相关的结构和功能脑磁共振成像（MRI）参数变化。
结论：该试验旨在为治疗PCS患者提供新的证据，主要关注那些表现出认知缺陷的人。通过这样做,它可以增强对潜在病理生理机制的理解，从而促进生物标志物研究，以促进我们对PCS患者的理解和治疗。
方法：招募标准包括对PCS的诊断，最小年龄为18岁，筛查时自我报告的认知障碍。在试验的第一阶段，总共418名参与者将被随机分配到verum或安慰剂干预。该试验将包括甲基强的松龙与安慰剂的第一阶段干预，为期六周，随后是6周的治疗中断期。随后，开放的第二阶段将为所有参与者提供甲基强的松龙，为期六周。门诊随访将在每次试验药物停止后两周进行。第三次也是最后一次后续行动，在第52周，将通过电话进行采访。主要结果测量了从基线到随访1（第8周）的多因素记忆问卷（MMQ）的记忆满意度子量表中15个或更多个点的患者内部变化。关键的次要结果包括从基线到随访2（第20周）的患者内记忆满意度的长期变化，其他MMQ分量表的变化(随访1和2)，以及神经心理学和认知评分的变化，以及通过关注生活质量的问卷进行的评估，疲劳,和情绪在同一时期。探索性结果涉及血清和脑脊液中的分子生物标志物变异，以及与认知相关的结构和功能脑磁共振成像（MRI）参数变化。
结论：该试验旨在为治疗PCS患者提供新的证据，主要关注那些表现出认知缺陷的人。通过这样做,它可以增强对潜在病理生理机制的理解，从而促进生物标志物研究，以促进我们对PCS患者的理解和治疗。
