Identification of factors impairing exercise capacity after severe COVID-19 pulmonary infection: a 3-month follow-up of prospective COVulnerability cohort

Abstract

Background Patient hospitalized for coronavirus disease 2019 (COVID-19) pulmonary infection can have sequelae such as impaired exercise capacity. We aimed to determine the frequency of long-term exercise capacity limitation in survivors of severe COVID-19 pulmonary infection and the factors associated with this limitation. Methods Patients with severe COVID-19 pulmonary infection were enrolled 3 months after hospital discharge in COVulnerability, a prospective cohort. They underwent cardiopulmonary exercise testing, pulmonary function test, echocardiography, and skeletal muscle mass evaluation. Results Among 105 patients included, 35% had a reduced exercise capacity (VO2peak < 80% of predicted). Compared to patients with a normal exercise capacity, patients with reduced exercise capacity were more often men (89.2% vs. 67.6%, p = 0.015), with diabetes (45.9% vs. 17.6%, p = 0.002) and renal dysfunction (21.6% vs. 17.6%, p = 0.006), but did not differ in terms of initial acute disease severity. An altered exercise capacity was associated with an impaired respiratory function as assessed by a decrease in forced vital capacity (p < 0.0001), FEV1 (p < 0.0001), total lung capacity (p < 0.0001) and DLCO (p = 0.015). Moreover, we uncovered a decrease of muscular mass index and grip test in the reduced exercise capacity group (p = 0.001 and p = 0.047 respectively), whilst 38.9% of patients with low exercise capacity had a sarcopenia, compared to 10.9% in those with normal exercise capacity (p = 0.001). Myocardial function was normal with similar systolic and diastolic parameters between groups whilst reduced exercise capacity was associated with a slightly shorter pulmonary acceleration time, despite no pulmonary hypertension. Conclusion Three months after a severe COVID-19 pulmonary infection, more than one third of patients had an impairment of exercise capacity which was associated with a reduced pulmonary function, a reduced skeletal muscle mass and function but without any significant impairment in cardiac function.

Evaluation of long-term sequelae by cardiopulmonary exercise testing 12 months after hospitalization for critical COVID-19

“…Impairment was predominantly related to persistent deconditioning or prior respiratory co-morbidities. These results confirm previous studies assessing exercise capacity by CPET 3 to 6 months after hospital release and reporting that remaining exercise limitation after COVID-19 is primarily related to physical deconditioning rather than to physiological impairment [5, 6, 17, 18]. Thus, recovery of physical capacities after a critical COVID-19 infection appears better than in patients with other ARDS etiologies [19, 20].…”

Reduced exercise capacity, chronotropic incompetence, and early systemic inflammation in cardiopulmonary phenotype Long COVID

“…One other group previously demonstrated that hsCRP, IL-6, and TNF-α are associated with reduced peak VO 2 three months after COVID-19 hospitalization. 36 Our findings suggest that higher levels of SARS-CoV-2 antibodies and inflammation during the early post-acute period are associated with lower peak VO 2 more than a year later. Elevated inflammatory markers, especially hsCRP, IL-6, and TNF-α could be due to higher severity of acute illness, 37 persistent immune activation, 38 and/or ongoing antigen stimulation from viral persistence.…”

“…58 Consistent with our findings that elevated hsCRP is associated with reduced exercise capacity, one other group found that hsCRP, IL-6, and TNF-alpha are associated with reduced peak VO 2 3 months after hospitalization for COVID-19. 59 Elevated inflammatory markers are associated with reduced exercise capacity and chronotropic incompetence among adolescents and adults with obesity. 44, 60 In heart failure, resting heart rate is positively associated with levels of hsCRP, but chronotropic incompetence during exercise is negatively correlated with copeptin (C-terminal portion of arginine) and norepinephrine levels.…”

Cardiopulmonary exercise testing to evaluate post-acute sequelae of COVID-19 (“Long COVID”): a systematic review and meta-analysis

“…Clinical variability may result from the spectrum of LC severity and symptomatology. 37 Although some studies suggest that acute severity may not impact exercise capacity, 38,39 most studies suggest higher acuity is associated with worse exercise capacity. 31,36,40-42 One study reported worse peak VO 2 among unvaccinated compared to vaccinated individuals.…”

“…Deconditioning was the most commonly identified pattern and the main cause of reduced exercise capacity reported by 8 studies. 39,40,42,46-51 Although ventilatory limitations were uncommon, multiple studies reported dysfunctional breathing or hyperventilation. 50,52-57 Muscular/peripheral oxygen extraction abnormalities were also commonly reported.…”