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: 10684750
• 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/10684750
• 关键词: Acceleration; Aging; Antioxidants; Arteries; Blood Vessels; 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; 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; body system; cerebrovascular; combat; coronavirus disease; cytokine; efficacy evaluation; evidence based guidelines; exercise rehabilitation; experience; functional independence; human old age (65+); 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诱导深层血管内皮功能障碍，其长期影响尚不清楚。 此外，在大量的Covid-19患者（〜30-40％）和 以疲劳，无力和神经认知缺陷的持续症状为特征 作为“长期杂种”。该项目的总体目的是评估Covid-19的长期后果 在老年退伍军人中，为基于血管内皮功能的科学明智建议 COVID-19之后的老年退伍军人和一般年长的退伍军人的康复。中心假设是， 鉴于氧化应激和注射在长长的血管内皮功能障碍中的基本作用 遵循Covid-19将与对健康和基于运动的长期负面影响有关 用线粒体靶向抗氧化剂（MITO-Q）补充的康复将协同改善 老年退伍军人的外周和脑血管内皮功能障碍，同时从康维德（Covid-19）康复。 该项目的基本原理是通过减少来改善COVID-19引起的血管内皮功能障碍 通过优化的康复进行氧化应激和炎症有可能改善退伍军人的健康状况 长期旋转，并改善老年退伍军人的发病率和死亡率。中心假设将是 通过追求两个具体目的测试：1）确定血管内皮的时间过程和健康风险 长期养老的老退伍军人的老年退伍军人的功能障碍，被录制的老兵和年长的退伍军人 谁从来没有共同和2）确定有或没有Mito-Q的基于运动的康复的效率 补充以改善长期老年退伍军人的老年退伍军人的血管内皮功能 他们被共同夺回的人和从未有过共同的老年退伍军人。在特定的目标1下，单一被动腿 移动（SPLM），流介导的字典（FMD）和呼吸持续加速度指数（BHAI）将用于 每年两次评估老年患者的微血管，导管伪像和脑血管内皮功能 4年以确定Covid-19对血管内皮功能的长期影响。另外，病人 在此期间，将跟踪健康风险，负结果，[神经认知功能和肺功能] 是时候确定周围和脑血管内皮功能评估的预后能力。 对于特定目标2，微血管（SPLM），导管动脉（FMD）和脑（Bhai）血管内皮 功能将在基于运动的康复或基于运动的康复之前和之后进行评估 结合补充MITO-Q，以确定其效率以改善周围和脑血管 一般而言，在互联的退伍军人和年长的退伍军人中，内皮功能。这项研究提出了 应用具有创新性，因为它专注于铅治疗候选者，以恢复外围和脑 血管内皮功能通过打击氧化应激持续升高的潜在问题和 与衰老相关的炎症，并进一步受到COVID-19的影响。拟议的研究很重要 因为预计它将为改善健康提供科学上合理的建议 在年长的退伍军人和那些努力从Covid-19中恢复的人。