Heat thErapy And mobiLity in COVID-19 Survivors

Post-acute sequelae of SARS-CoV-2 infection (PASC) affects 5 out of 10 patients hospitalized for the coronavirus disease 2019 (COVID-19) and \~11% of all adults infected by SARS-CoV-2, which makes this condition a growing public health concern. It is associated with important disabilities, cognitive dysfunction, and increased risks for cardiovascular and metabolic diseases. Although exercise-based intervention is a promising rehabilitation strategy, participation rates are commonly low in clinical population. In addition, post-exertional malaise, a common symptom with PASC, is a major safety concern in these patients, which may prevent a significant proportion of these individuals to receive adequate rehabilitation. In this context, there is a critical need to develop well-tolerated and effective strategies at home that ameliorates health and functional capacity in individuals with PASC. One promising approach that offers numerous health benefits is whole-body heat therapy. Whether this intervention is effective when confined to the lower body and well tolerated at home in people with PASC is, however, unknown. The overall objective of this project is to determine the safety, tolerability, and efficacy of home-based lower body heat therapy in late middle-age and older adults with PASC. Investigators will test the central hypothesis that home-based lower body heat therapy is safe, well adhered, and can improve functional capacity and several surrogate markers for metabolic and vascular health in late-middle age and older adults with PASC. Specific Aim 1 will test the hypothesis that lower body heat therapy at home is safe, well adhered, and improve both cognitive and physical function in middle-age and older adults with PASC. Selected participants will be randomly allocated to perform 8 weeks of home-based lower body heat therapy (HT, skin temperature 38-40˚C, 40-55 min, 5 per week at home), a thermoneutral condition (CT, skin temperature 33˚C, same duration and frequency), or a walking intervention using wearable technology (WT, 1,500-3,000 additional steps from baseline, 3-5 days per week). We will compare the 6 min walking distance, the short physical performance battery test score, gait speed, cognitive function, incidence of adverse events, and participant's adherence to intervention between groups. Specific Aim 2 will test the hypothesis that heat therapy will attenuate inflammation, which will then decrease arterial stiffness, and improve both vascular endothelial function and muscle intracellular oxygen availability in participants with PASC. Investigators will use in vitro assays on blood samples and Doppler ultrasound techniques to assess changes in inflammation, redox status, pulse-wave velocity, and flow-mediated dilation. Muscle intracellular oxygen availability will be measured by magnetic resonance spectroscopy in vivo. Specific Aim 3 will test the hypothesis that lower body heat therapy will improve glucose control as a result of enhanced mitochondrial function. All these effects will not be statistically inferior to the WT group. The proposed research is highly significant as it is easily translatable and is expected to guide future rehabilitation strategies to mitigate long-term disabilities in patients with PASC.