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Principal Investigator: ALICE S. RYAN
Organization: SOUTH TEXAS VETERANS HEALTH CARE SYSTEM
Fiscal Year: 2024
Funding agency: Veterans Affairs
Findings of post-acute sequelae of Post-COVID Conditions (PCC) manifestations of fatigue, pain, dyspnea,
and muscle weakness, provide a strong rationale for rehabilitation; yet few formal studies exist and the effects
of severe acute respiratory syndrome coronavirus-2 infection on function are not well described. Notably, two-
thirds of Veterans are overweight and obese, rendering excess adiposity a significant risk factor and a high-
priority area related to PCC prevention and care. Obesity increases the risk of severe illness in Veterans
recovering from PCC, but how it does so is not fully understood.
Recent research suggests that excess adipose tissue is associated with adverse changes in adipose
cellular function, and that these variations may be involved in the biology of aging and the etiology of aging-
related diseases. Adipose tissue contains cells that have undergone cellular senescence, which induces
inflammation, cytotoxicity, and metabolic dysfunction in other cells and tissues. However, the precise role of
adipose tissue cellular composition on PCC recovery is limited.
Thus, we propose to evaluate the role of obesity and PCC on physical functioning, health-related quality of
life (HRQOL), and systemic and adipose tissue inflammatory and cellular senescence profiles in ethnically
diverse older Veterans from the Audie Murphy (San Antonio) and Baltimore VA Medical Centers. Further, we
propose a randomized controlled trial to determine whether a reduction in body weight and increased physical
function by a weight loss intervention (WL), including dietary modification and exercise, in obese Veterans with
PCC will reduce systemic and adipose tissue inflammation and senescence, which will have important
implications for PCC recovery. We will pursue the following aims:
Aim 1: To compare physical function, body composition, HRQOL, PCC symptoms, and adipose tissue
molecular profiling in four cohorts of Veterans at baseline: lean PCC naïve, lean with PCC, obese PCC naïve,
and obese with PCC (N=150).
Aim 2: To compare in Veterans with obesity: a) a 12-week randomized WL vs. weight stability (WS)
intervention (30/group) on physical function, body composition, HRQOL, and PCC symptoms together with
changes in the global molecular profile in adipose tissue in Veterans with PCC and b) the WL intervention in
PCC naïve vs. with PCC (N=30/group) on these outcomes.
Older (55-80 years) men and women Veterans will be recruited. We will perform a standard functional
battery (maximal aerobic capacity [VO2max; primary outcome], usual gait speed, six min walk distance, timed
up and go, and handgrip strength), body composition (dual energy x-ray absorptiometry and computed
tomography scans), HRQOL (NIH PROMIS-57), and PCC symptoms (COVID-19 Yorkshire Rehabilitation
Scale [C19-YRS]) and adipose tissue will be collected. Further, we will test, in a randomized controlled trial, the
hypothesis that a WL intervention, compared to weight stability (WS), improves physical function, body
composition, and HRQOL and reduces inflammation and senescent cell burden and to a similar extent as the
PCC naïve group with obesity.
A deeper understanding of the relationship between adipose tissue and PCC will likely reveal factors that
predispose to or protect against aging-related functional declines. Moreover, a better understanding of the
effects of a lifestyle intervention on the molecular profile of adipose tissue will help to determine how changes
in adipose tissue contribute to PCC and PCC recovery. Lastly, this research will provide important mechanistic
insights into how cellular senescence influences the pathophysiology of physical, mental, and social
dysfunction in older Veterans. Our findings could provide evidence-based recommendations to promote this
type of intervention in Veterans recovering from PCC.
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