Evaluating the Long-term Health Consequences of COVID-19 and Rehabilitation Therapies to Speed Convalescence

评估 COVID-19 的长期健康影响和加速康复的康复治疗

• 批准号: 10534494
• 负责人: Russell S. Richardson
• 金额: --
• 依托单位: VA SALT LAKE CITY HEALTHCARE SYSTEM
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-01 至 2027-10-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10534494
• 关键词: Acceleration; Address; Age; Aging; Antioxidants; Arteries; COVID-19; COVID-19 impact; COVID-19 patient; COVID-19 severity; COVID-19 survivors; COVID-19 treatment; Cardiovascular system; Cerebrum; Chronic Disease; Communities; Convalescence; Data; Disease; Disease Progression; Dyspnea; Elderly; Event; Exercise; Fatigue; Fostering; Free Radicals; Health; High Prevalence; Impairment; Incidence; Inflammation; Inflammatory; Knowledge; Lead; Leg; Link; Long COVID; Mediating; Mission; Mitochondria; Morbidity - disease rate; Movement; Neurocognitive; Neurocognitive Deficit; Outcome; Oxidative Stress; Patients; Peripheral; Play; Predisposition; Quality of life; Reactive Oxygen Species; Recommendation; Recovery; Rehabilitation therapy; Reporting; Research; Risk; Risk Factors; Role; SARS-CoV-2 positive; Scientific Advances and Accomplishments; Speed; Supplementation; Symptoms; System; Testing; Time; Vascular Endothelium; Vasodilation; Veterans; age related; base; body system; cerebrovascular; combat; coronavirus disease; cytokine; evidence based guidelines; experience; functional independence; improved; indexing; innovation; long term consequences of COVID-19; long-term sequelae; military veteran; mortality; older patient; persistent symptom; prognostic value; pulmonary function; severe COVID-19; sound; therapeutic candidate; vascular endothelial dysfunction

COVID-19 induces profound vascular endothelial dysfunction, the long-term impact of which is unknown. Moreover, recovery from COVID-19 is delayed in a substantial number of COVID-19 patients (~ 30-40%) and characterized by persistent symptoms of fatigue, weakness, and neurocognitive deficits commonly referred to as “long-COVID”. The overall objective of this project is to evaluate the long-term consequences of COVID-19 in older Veterans and provide scientifically sound recommendations for vascular endothelial function-based rehabilitation in older Veterans after COVID-19 and older Veterans in general. The central hypothesis is that, given the fundamental role of oxidative stress and inflammation in long-COVID, vascular endothelial dysfunction following COVID-19 will be associated with long-term negative impacts on health and exercise-based rehabilitation with mitochondria-targeted antioxidant (Mito-Q) supplementation will synergistically improve peripheral and cerebral vascular endothelial dysfunction in older Veterans while convalescing from COVID-19. The rationale for this project is that improving COVID-19-induced vascular endothelial dysfunction by decreasing oxidative stress and inflammation with optimized rehabilitation has the potential to improve health in Veterans with long-COVID, and improve both morbidity and mortality in older Veterans. The central hypothesis will be tested by pursuing two Specific Aims: 1) determine the time course and health risks of vascular endothelial dysfunction in older Veterans with long-COVID, older Veterans who are COVID-recovered, and older Veterans who never had COVID and 2) determine the efficacy of exercise-based rehabilitation with and without Mito-Q supplementation to improve vascular endothelial function in older Veterans with long-COVID, older Veterans who are COVID-recovered, and older Veterans who never had COVID. Under Specific Aim 1, single passive leg movement (sPLM), flow-mediated dilation (FMD), and the breath-hold acceleration index (BHAI) will be used to evaluate microvascular, conduit artery, and cerebral vascular endothelial function in older patients twice annually for 4 years to determine long-term impact of COVID-19 on vascular endothelial function. Additionally, patient health risks, negative outcomes, [neurocognitive function, and pulmonary function] will be tracked during this time to determine the prognostic ability of the peripheral and cerebral vascular endothelial function assessments. For Specific Aim 2, microvascular (sPLM), conduit artery (FMD), and cerebral (BHAI) vascular endothelial function will be assessed before and after either exercise-based rehabilitation or exercise-based rehabilitation combined with Mito-Q supplementation to determine their efficacy to improve peripheral and cerebral vascular endothelial function in COVID-impacted Veterans and older Veterans in general. The research proposed in this application is innovative because it focuses on lead therapeutic candidates to rehabilitate peripheral and cerebral vascular endothelial function by combatting the underlying issue of a sustained elevation in oxidative stress and inflammation associated with aging and further impacted by COVID-19. The proposed research is significant because it is expected to provide scientifically sound recommendations for rehabilitation to improve health in older Veterans and those struggling to recover from COVID-19.

COVID-19 会引起严重的血管内皮功能障碍，其长期影响尚不清楚。 此外，大量 COVID-19 患者 (~ 30-40%) 的恢复时间较晚，并且 其特征是持续的疲劳、虚弱和神经认知缺陷症状，通常称为 该项目的总体目标是评估 COVID-19 的长期后果。 为老年退伍军人提供基于血管内皮功能的科学合理的建议 COVID-19 后老年退伍军人和一般老年退伍军人的康复中心假设是， 鉴于氧化应激和炎症在长期新冠肺炎、血管内皮功能障碍中的根本作用 遵循 COVID-19 将对健康和基于运动的长期负面影响相关 补充线粒体靶向抗氧化剂（Mito-Q）将协同改善康复 老年退伍军人在 COVID-19 康复期间的外周和脑血管内皮功能障碍。 该项目的基本原理是通过减少 氧化应激和炎症通过优化康复有可能改善退伍军人的健康 并改善老年退伍军人的发病率和死亡率。 测试所追求的两个具体目标：1）确定血管内皮细胞的时间进程和健康风险 长期感染新冠病毒的老年退伍军人、新冠病毒康复的老年退伍军人以及老年退伍军人的功能障碍 从未患过新冠病毒的人以及 2) 确定使用或不使用 Mito-Q 的基于运动的康复的效果 补充药物以改善患有长期新冠肺炎的老年退伍军人的血管内皮功能 已康复的新冠肺炎患者以及从未患过新冠肺炎的老年退伍军人 根据特定目标 1，单腿被动。 运动 (sPLM)、血流介导扩张 (FMD) 和屏气加速指数 (BHAI) 将用于 每年两次评估老年患者的微血管、导管动脉和脑血管内皮功能 另外，为期 4 年以确定 COVID-19 对患者血管内皮功能的长期影响。 在此期间将跟踪健康风险、负面结果、[神经认知功能和肺功能] 确定预后能力的时间是外周血管和脑血管内皮功能的评估。 对于特定目标 2，微血管 (sPLM)、导管动脉 (FMD) 和脑 (BHAI) 血管内皮 将在基于运动的康复或基于运动的康复之前和之后评估功能 与 Mito-Q 补充剂相结合，以确定其改善外周和脑血管的功效 这项研究提出了受新冠肺炎影响的退伍军人和老年退伍军人的内皮功能。 该应用程序具有创新性，因为它专注于恢复外周和大脑功能的主要治疗候选药物 通过对抗氧化应激持续升高的根本问题来改善血管内皮功能 与衰老相关的炎症以及受 COVID-19 进一步影响的炎症这项研究具有重要意义。 因为它有望为改善健康的康复提供科学合理的建议 老年退伍军人和那些努力从 COVID-19 中恢复的人。