Eccentric Training in Pulmonary Rehabilitation of Post-COVID-19 Patients: An Alternative for Improving the Functional Capacity, Inflammation, and Oxidative Stress

Abstract

The purpose of this narrative review is to highlight the oxidative stress induced in COVID-19 patients (SARS-CoV-2 infection), describe longstanding functional impairments, and provide the pathophysiologic rationale that supports aerobic eccentric (ECC) exercise as a novel alternative to conventional concentric (CONC) exercise for post-COVID-19 patients. Patients who recovered from moderate-to-severe COVID-19 respiratory distress demonstrate long-term functional impairment. During the acute phase, SARS-CoV-2 induces the generation of reactive oxygen species that can be amplified to a "cytokine storm". The resultant inflammatory and oxidative stress process causes organ damage, particularly in the respiratory system, with the lungs as the tissues most susceptible to injury. The acute illness often requires a long-term hospital stay and consequent sarcopenia. Upon discharge, muscle weakness compounded by limited lung and cardiac function is often accompanied by dyspnea, myalgia, anxiety, depression, and sleep disturbance. Consequently, these patients could benefit from pulmonary rehabilitation (PR), with exercise as a critical intervention (including sessions of strength and endurance or aerobic exercises). Unfortunately, conventional CONC exercises induce significant cardiopulmonary stress and increase inflammatory and oxidative stress (OS) when performed at moderate/high intensity, which can exacerbate debilitating dyspnoea and muscle fatigue post-COVID-19. Eccentric training (ECC) is a well-tolerated alternative that improves muscle mass while mitigating cardiopulmonary stress in patients with COPD and other chronic diseases. Similar benefits could be realized in post-COVID-19 patients. Consequently, these patients could benefit from PR with exercise as a critical intervention.

Keywords: exercise; physical activity; post-COVID-19; rehabilitation.

Figure 1

Postulated sequence that generates reactive oxygen species from SARS-CoV-2. SARS-CoV-2 infection induces a decrease in ACE2 that causes Ang II to increase, which activates NADPH oxidase (NOX). This generates superoxide anion (O₂^·−) and other oxygen radicals—peroxynitrite, hydrogen peroxide and hydroxyl radical. The reactive oxygen species inflict cellular damage, further activate inflammatory cells, and amplify the increased release of cytokines. Abbreviations: ACE2, angiotensin–converting enzyme 2; Ang II, angiotensin II.

Figure 2

Overview of the factors involved in the deterioration of the functional capacity, self-autonomy, and health-related to quality of life in post-COVID-19 patients that need to be addressed by pulmonary rehabilitation. Abbreviations: IL = interleukin; IFN–γ = interferon gamma; TNF–α = tumor necrosis factor alpha; O₂⁻ = anion superoxide; H₂O₂ = hydrogen peroxide; OH⁻ = hydroxyl ion; NO⁻ = nitric oxide; NO₂⁻ = nitrite; NO₃⁻ = nitrate; ONOO⁻ = peroxynitrite; 8–iso PGF2α = 8–iso–prostagladin F2–alpha; SOD = superoxide dismutase; GPX = glutathione peroxidase; CAT = catalase; 6mWT = six-minute walking test; VO₂-peak = peak oxygen uptake.

Figure 3

Overview of concentric and eccentric exercises (as the main components of the movement) on the cardiopulmonary and muscle systems, symptoms associated with these exercises, and their effects on redox balance.