COVID-19, Chronic Adaptation and Response to Exercise (COVID-CARE): A Randomized Controlled Trial

2019年底作为一种新型冠状病毒出现的SARS-CoV-2(新冠肺炎)导致了一场大流行，影响了全球数以百万计的人。随着临床医生和科学家对最初新冠肺炎感染的各种表现和表现有了更好的了解，人们的注意力现在转向了新冠肺炎的康复轨迹和长期后遗症。许多住院患者需要与危重疾病和延长住院时间相关的后续护理，然而，即使那些从未住院和/或最初出现轻微新冠肺炎症状的患者，仍需要康复治疗。据估计，23%的新冠肺炎康复者将出现新冠肺炎急性后遗症，这是影响日常功能和生活质量的持续性症状。据报道，疲劳、呼吸困难、胸痛/胸闷是常见的持续性身体症状，以及焦虑/抑郁和认知主诉等心理症状。有效利用有氧运动训练作为一种心肺功能康复干预方式，可以对患者的功能和生活质量产生高度的影响。 这项随机对照试验的总体目标是确定AET是否有利于改善新冠肺炎幸存者的功能结果和康复。所有参与者都将进行基线评估，包括身体、认知测试、患者报告的结果和血管功能。之后，参与者将被随机分到两组中的任何一组，为期10周：1)有氧运动训练+教育组(AET+)，或2)只接受教育的等待名单对照组(CON)。10周后，两组都将重复与基线相同的评估(10周随访)。在这次访问之后，CON组的参与者将交叉进行现场或远程的10周AET，然后进行第三次评估访问(20周随访)。参与者还将在基线研究访问时开始佩戴手表加速度计，并一直到后续时间点(AET+10周，CON 20周)，以持续收集自由生活的身体活动和睡眠质量。此外，所有参与者将在一年内定期接受监测，以记录一段时间内的体力活动、睡眠质量和与健康相关的生活质量结果。 招募将在长期恢复阶段和参与者不再具有传染性时进行。主要的结果衡量标准是6分钟步行测试中的步行距离，次要结果变量包括患者报告的结果、自由生活的体力活动和睡眠质量。探索性结果包括最大运动试验期间心肺功能的测量(如肺气体交换)、血管功能、临床结果、认知、血液生物标记物、代谢组学和基于超声的肌肉测量。我们正在与多个NIH研究所合作，利用他们的专业知识/资源实现多系统方法。在研究设计中使用交叉控制组将允许检查新冠肺炎幸存者的身体功能、生活质量、自由生活体力活动和睡眠质量的自发恢复情况。 注册科目总数=41 本年度报考科目总数=8 筛选失败的注册科目总数=4 退出的注册科目总数=5 目前的研究旨在探讨AET改善新冠肺炎幸存者预后的可行性，这些幸存者报告持续疲劳和/或身体功能障碍影响他们的日常生活。有效利用有氧运动作为康复干预措施可能会对新冠肺炎幸存者的个人和公共健康结果产生高度影响。 截至23财年末，11名受试者已完成现场研究程序，并处于1年随访期。20名受试者已经完全完成了这项研究。没有严重的不良事件可供报告。这项研究正在收集阶段，我们正在积极招募和招募参与者。

The emergence of SARS-CoV-2 as a novel coronavirus at the end of 2019 (COVID-19) resulted in a pandemic that has affected millions of people worldwide. While clinicians and scientists have gained a better understanding of the various presentations and manifestations of the initial COVID-19 infection, attention has now turned to the recovery trajectory and long-term sequelae of COVID-19. Many hospitalized people require follow-up care related to critical illness and prolonged hospitalization, however there remains a rehabilitation need even among those that were never hospitalized and/or initially presented with milder symptoms of COVID-19. Referred to commonly as long-haulers or long-COVID, it is estimated that 23% of those recovered from COVID-19 will experience Post-Acute Sequelae of COVID-19 (PASC), that is persistent symptoms affecting daily functioning and quality of life. Fatigue, dyspnea, chest pain/tightness have been reported as common persistent physical symptoms, as well as psychological symptoms such as anxiety/depression and cognitive complaints. Effective use of aerobic exercise training as a cardiorespiratory, rehabilitative intervention could have a high degree of impact on patient functional and quality of life outcomes. The overall aim of this randomized controlled trial is to determine whether AET is beneficial for improving functional outcomes and recovery among survivors of COVID-19. All participants will perform baseline assessments including physical, cognitive testing, patient-reported outcomes, and vascular function. Thereafter, participants will be randomized to either one of 2 arms for 10 weeks: 1) an aerobic exercise training with education (AET+) group, or 2) a wait-list control group (CON) provided with education only. After 10 weeks, both groups will repeat the same assessments as performed at baseline (10-week follow-up). Following this visit, participants in the CON group will crossover and perform 10 weeks of AET either on-site or remotely, followed by a third assessment visit (20-week follow-up). Participants will also begin wearing a wristwatch accelerometer at the baseline study visit and through to the follow-up time point (10 weeks for AET+, 20 weeks for CON), for continuous collection of free-living physical activity and sleep quality. In addition, all participants will be monitored periodically over one year to capture physical activity, sleep quality and health-related QOL outcomes over time. Recruitment will occur during the phase of long-term recovery and when participants are no longer infectious. The primary outcome measure is distance walked during a 6-minute walk test, and secondary outcome variables include patient-reported outcomes, free-living physical activity and sleep quality. The exploratory outcomes include measures of cardiorespiratory capacity during a maximal exercise test (such as pulmonary gas exchange), vascular function, clinical outcomes, cognition, blood biomarkers, metabolomics, and ultrasound-based muscle measurements. We are collaborating with various NIH institutes to capitalize on their expertise/resources for a multi-systems approach. The use of a crossover control group in the study design will allow examination of the spontaneous recovery for physical function, quality of life outcomes, free-living physical activity and sleep quality among survivors of COVID-19. Total Number of Subjects Enrolled = 41 Total Number of Subjects Enrolled in the current year = 8 Total Number of Subjects Enrolled that are screen failures = 4 Total Number of Subjects Enrolled that withdrew = 5 The current study aims to examine the feasibility of AET for improving outcomes in survivors of COVID-19 that report persistent fatigue and/or physical dysfunction affecting their daily lives. The effective use of aerobic exercise as a rehabilitative intervention could have a high degree of impact on personal and public health outcomes for COVID-19 survivors. By the end of FY23, 11 subjects had completed on-site study procedures and were in the 1-year follow-up period. Twenty subjects had fully completed participation in the study. There were no serious adverse events to report. The study is in the collection phase and we are actively recruiting and enrolling participants.