Oxygen uptake kinetics and chronotropic responses to exercise are impaired in survivors of severe COVID-19.

The post-acute phase of coronavirus disease 2019 (COVID-19) is often marked by several persistent symptoms and exertional intolerance, which compromise survivors' exercise capacity. This was a cross-sectional study aiming to investigate the impact of COVID-19 on oxygen uptake (V̇o 2 ) kinetics and cardiopulmonary function in survivors of severe COVID-19 about 3-6 mo after intensive care unit (ICU) hospitalization. Thirty-five COVID-19 survivors previously admitted to ICU (5 ± 1 mo after hospital discharge) and 18 controls matched for sex, age, comorbidities, and physical activity level with no prior history of SARS-CoV-2 infection were recruited. Subjects were submitted to a maximum-graded cardiopulmonary exercise test (CPX) with an initial 3-min period of a constant, moderate-intensity walk (i.e., below ventilatory threshold, VT). V̇o 2 kinetics was remarkably impaired in COVID-19 survivors as evidenced at the on-transient by an 85% ( P = 0.008) and 28% ( P = 0.001) greater oxygen deficit and mean response time (MRT), respectively. Furthermore, COVID-19 survivors showed an 11% longer ( P = 0.046) half-time of recovery of V̇o 2 (T 1/2 V̇o 2 ) at the off-transient. CPX also revealed cardiopulmonary impairments following COVID-19. Peak oxygen uptake (V̇o 2peak ), percent-predicted V̇o 2peak , and V̇o 2 at the ventilatory threshold (V̇o 2VT ) were reduced by 17%, 17%, and 12% in COVID-19 survivors, respectively (all P < 0.05). None of the ventilatory parameters differed between groups (all P > 0.05). In addition, COVID-19 survivors also presented with blunted chronotropic responses (i.e., chronotropic index, maximum heart rate, and heart rate recovery; all P < 0.05). These findings suggest that COVID-19 negatively affects central (chronotropic) and peripheral (metabolic) factors that impair the rate at which V̇o 2 is adjusted to changes in energy demands. NEW & NOTEWORTHY Our findings provide novel data regarding the impact of COVID-19 on submaximal and maximal cardiopulmonary responses to exercise. We showed that V̇o 2 kinetics is significantly impaired at both the onset (on-transient) and the recovery phase (off-transient) of exercise in these patients. Furthermore, our results suggest that survivors of severe COVID-19 may have a higher metabolic demand at a walking pace. These findings may partly explain the exertional intolerance frequently observed following COVID-19.