The proposed focuses on improving both morbidity and mortality in older Veterans andthose recovering from COVID-19 by developing rehabilitation therapies to augment vascularendothelial function by combating the oxidative stress and inflammation associated withaging and further induced by COVID-19. The investigators expected outcomes will have animportant positive impact because they will provide scientifically sound recommendationsfor rehabilitation to improve vascular endothelial function and minimize the long-termconsequences of COVID-19.
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.
Dietary Supplement: Mitoquinone
Mito-Q is a supplement that targets mitochondrial function. Linking a
triphenyl-phosphonium cation to coenzyme-Q, to produce Mito-Q, results in a lipophilic
compound, which, due to the large mitochondrial membrane potential, selectively
accumulates within mitochondria. This targeted antioxidant approach results in 50- to
100-fold more Mito-Q accumulation compared to non-targeted antioxidant delivery.
Other Name: MitoQ
Dietary Supplement: Placebo
A placebo will be used in combination with exercise rehabilitation allowing for a double
blinded placebo controlled design.
Inclusion Criteria:
- 50 years of age or greater
- Long-COVID and COVID-recovered patients must have SARS-CoV-19 positive test near the
time of COVID-19 diagnosis
- Long-COVID and COVID-recovered patients must be 3-12 months post-initial COVID-19
diagnosis
- Ability to sign informed consent
Exclusion Criteria:
- BMI >45 kg/m2
- Unstable (<6 months) or severe coronary artery disease (CAD-RADS score = 4A),
peripheral artery disease (Ankle Brachial Index <0.40), cerebrovascular disease
(identified by previous stroke in last 12 months), severe COPD (=Stage III),
uncontrolled hypertension (>160/100 mmHg), chronic kidney disease requiring
dialysis, severe renal insufficiency (creatinine clearance <30 by the
Cockcroft-Gault formula), Alzheimer's disease, dementia
- Orthopedic limitations that would prohibit exercise
- [Current smokers and individuals that stopped smoking in the last 10 years]
- Already taking Mito-Q or unwilling to cease dietary supplements for participation
- Any other condition or event considered exclusionary by the PIs or a physician
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, United States
Investigator: P Jon White, MD
Contact: (801) 582-1565
Paul.White2@va.gov
Investigator: Joel Douglas Trinity, PhD
Joel D Trinity, PhD
(801) 582-1565 - 1199
Joel.Trinity@va.gov
Russell S Richardson, PhD
(801) 582-1565 - 4344
r.richardson@hsc.utah.edu
Joel Douglas Trinity, PhD, Principal Investigator
VA Salt Lake City Health Care System, Salt Lake City, UT