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.