Fatigue and Fatigability in Veterans Following SARS-CoV-2 Infection

Project Summary/Abstract The chronic presence of elevations in fatigue suggests that individuals with post-COVID-19 fatigue (PCF) may be at risk for experiencing increased fatigability when engaging in physical activity. An individual's level of fatigability is determined by the interactions between objective declines in performance (performance fatigability) and perceptual changes regulating activity performance (i.e., perceived fatigability). Skeletal muscle alterations including reduced force capacity, fiber atrophy, and metabolic dysfunction have been observed in patients following SARS-CoV-2 infection. In addition, depression and anxiety have been identified as common pre-existing conditions in patients with PCF. Thus, psychological as well as physiological consequences of SARS-CoV-2 may provide insight into co-occurring mechanisms by which increased fatigability occurs and persists following SARS-CoV-2 infection. While there have been widespread calls for the implementation of rehabilitation for individuals recovering from SARS-CoV-2 infection, relatively little is known about the potential benefits of physical exercise in this population. Home-based exercise programs maybe particularly advantageous due to its ability to provide an exercise option to combat sedentary behavior imposed by lockdowns, quarantines, and restrictions on community activity caused by the COVID-19 pandemic. To date, the safety and feasibility of home-based exercise has yet to be thoroughly investigated in people previously infected by SARS-CoV-2. The overall goal of this project is to advance our understanding of underlying mechanisms impacting performance fatigability and perceived fatigability in Veterans with PCF and explore the safety and feasibility of a home-based "minimal-dose" resistance exercise program in this population. The central hypothesis is that declines in force capacity, skeletal muscle oxygen extraction, and affective responses to physical activity offer potential mechanisms through which fatigability is increased in Veterans with PCF. Moreover, home-based resistance exercise delivered remotely may provide a safe and feasible treatment option for this population. To address this hypothesis, the following aims are proposed: Aim 1: Compare fatigability, and the underlying neuromuscular and neurobiological factors, in Veterans with post- COVID-19 fatigue to Veterans previously infected by SARS-CoV-2 without fatigue. Hypothesis 1a. Veterans with post-COVID-19 fatigue will exhibit greater performance fatigability and perceived fatigability compared to Veterans previously infected with SARS-CoV-2 not reporting post-COVID-19 fatigue. Hypothesis 1b. Veterans with post-COVID-19 fatigue will exhibit reductions in knee extensor force capacity, muscle oxygen extraction, and affective valence compared to Veterans previously infected with SARS-CoV-2 not reporting post-COVID-19 fatigue. Aim 2: Determine the safety and feasibility of an 8-week home-based "minimal-dose" resistance exercise program for Veterans with post-COVID-19 fatigue. Hypothesis 2a. 8 weeks of home-based minimal- dose resistance exercise will be safe and feasible in Veterans with post-COVID-19 fatigue. To test aim 2, we will use a randomized controlled feasibility trial. Skeletal muscle force will be assessed during isometric and dynamic knee extensor contractions using dynamometry and muscle oxygen extraction of the vastus lateralis will be estimated using near-infrared spectroscopy. Affective responses will be measured using the Feeling Scale. Secondary measures include motor unit properties, functional outcomes, and health-related quality of life.