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Principal Investigator: GWENAEL LAYEC
Organization: UNIVERSITY OF NEBRASKA OMAHA
Fiscal Year: 2024
Award: $665,766
Funding agency: National Institute on Aging
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. We 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 O2 availability in individuals with PASC. We 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 O2 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.
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SARS-CoV2><Post Acute Sequelae of severe acute respiratory syndrome coronavirus 2><Post-Acute Sequelae of SARS-CoV-2 Infection><Public Health><Pulse><Random Allocation><Random Selection><Randomized><Recovery of Function><Redox><Reduced mobility><Reduction in mobility><Rehabilitation><Rehabilitation therapy><Reporting><Research><Risk><Risk Factors><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 infection><SARS-CoV2><SARS-CoV2 infection><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><Safety><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute 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strategy><rehabilitative><rehabilitative paradigms><rehabilitative therapy><restore function><restore functionality><restore lost function><surrogate bio-markers><surrogate biomarkers><three-arm study><vascular><vascular dysfunction><vasculopathy><walking intervention><wearable><wearable device><wearable electronics><wearable system><wearable technology><wearable tool><wearables>