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

2019年底出现的新型冠状病毒SARS-CoV-2（COVID-19）导致全球数百万人受到影响。虽然临床医生和科学家对最初COVID-19感染的各种表现和表现有了更好的了解，但现在注意力已转向COVID-19的恢复轨迹和长期后遗症。许多住院患者需要与危重疾病和长期住院相关的后续护理，然而，即使是从未住院和/或最初出现COVID-19症状较轻的患者，也仍然需要康复。通常被称为长途运输者或长期COVID，据估计，23%的COVID-19康复者将出现COVID-19急性后后遗症（PASC），即影响日常功能和生活质量的持续症状。疲劳、呼吸困难、胸痛/胸闷已被报告为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。有效使用有氧运动训练作为心肺康复干预，可能对患者的功能和生活质量结果产生高度影响。 这项随机对照试验的总体目标是确定AET是否有利于改善COVID-19幸存者的功能结局和恢复。所有参与者将进行基线评估，包括身体，认知测试，患者报告的结果和血管功能。此后，参与者将被随机分配到2组中的任一组，持续10周：1）有氧运动训练+教育（AET+）组，或2）仅提供教育的等待名单对照组（CON）。10周后，两组将重复基线时进行的相同评估（10周随访）。在此次访视后，CON组的受试者将交叉并在现场或远程进行10周的AET，然后进行第三次评估访视（20周随访）。受试者还将在基线研究访视时开始佩戴腕表加速度计，直至随访时间点（AET+为10周，CON为20周），以连续收集自由生活体力活动和睡眠质量。此外，所有参与者将在一年内定期接受监测，以捕获随时间推移的身体活动，睡眠质量和健康相关QOL结果。 招募将在长期恢复阶段和受试者不再具有传染性时进行。主要结局指标是6分钟步行试验中的步行距离，次要结局变量包括患者报告的结局、自由生活体力活动和睡眠质量。探索性结局包括最大运动试验期间的心肺功能测量（如肺气体交换）、血管功能、临床结局、认知、血液生物标志物、代谢组学和基于超声的肌肉测量。我们正在与各个NIH研究所合作，利用他们的专业知识/资源进行多系统方法。在研究设计中使用交叉对照组将允许检查COVID-19幸存者的身体功能、生活质量结局、自由生活体力活动和睡眠质量的自发恢复。 入组的受试者总数= 41 当年入组的受试者总数= 8 筛选失败的入组受试者总数= 4 入组但退出的受试者总数= 5 目前的研究旨在研究AET改善COVID-19幸存者结局的可行性，这些幸存者报告持续疲劳和/或影响日常生活的身体功能障碍。有效使用有氧运动作为康复干预措施可能对COVID-19幸存者的个人和公共健康结果产生高度影响。 截至2023财年末，11例受试者完成了现场研究程序，并处于1年随访期。20例受试者完全完成了研究参与。未报告严重不良事件。该研究处于收集阶段，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.