Introduction
The mechanisms underlying symptoms of persistent fatigue and severe exercise intolerance which can follow SARS-CoV-2 infection, termed 'Long COVID' (LC), are not fully understood. The objective of this study was to compare whole-body cardiopulmonary fitness (V̇O2) and local skeletal muscle measures of oxygen consumption (musV̇O2), oxidative capacity (τ) and microvascular reactivity (post-occlusive reactive hyperaemia (PORH)) between individuals with LC and healthy controls (HC).
Methods
Participants with LC were recruited from the University College London Hospital (UCLH) Long COVID Clinic and HC from students and staff at University College London. Cardiopulmonary fitness was measured using analysis of expired gases during a sub-maximal (85% of predicted maximum heart rate) ramp cardiopulmonary exercise test (CPET) performed on a semi-recumbent cycle ergometer. Near Infrared Spectroscopy (NIRS) was applied to the gastrocnemius in combination with arterial occlusions and a short bout of muscle contractions for assessment of local skeletal muscle oxygen consumption (musV̇O2), oxidative capacity (recovery of musV̇O2, τ) and microvascular time to 95% PORH. Descriptive statistics are presented as n(%) and mean±standard deviation. Outcome measures were compared between LC and HC using potential outcome means (POMs) calculated by an augmented inverse probability weighted estimator with a linear outcome model and logit treatment model. Estimates were adjusted for potential confounders (age, sex and ethnicity) and are summarised as POM(95% confidence intervals). The level of significance was set at p<0.05.
Results
Analysis includes 32 adults (10(31%) men, 44±12 years old) with LC and 19 HC (6(32%) men, 40±13 years old). In patients with LC, cardiopulmonary fitness was lower (V̇O2 at Anaerobic Threshold (AT): 12.8(11.7,13.9) versus 16.3(15.0,17.5) ml/Kg/min, p<0.001; AT: 47.7(44.1,51.2) versus 56.6(53.1,60.0) % of predicted V̇O2max, p<0.001; V̇O2 Work Rate: 8.5(8.1,9.0) versus 9.4(9.0,9.8) ml/min/W, p=0.008), oxidative capacity was poorer (τ: 38.7(31.9,45.6) versus 24.6(19.1,30.1) seconds, p=0.001) and resting musV̇O2 was lower (0.11(0.08,0.15) versus 0.15(0.12,0.18) µM/s, p=0.09) compared to healthy controls. There were no observed differences for time to 95% PORH between the groups (28.0(23.7,32.3) versus 27.3(22.3,32.4) seconds, p=0.86).
Conclusion
Results from this study suggest that, compared to healthy controls, individuals living with Long COVID have lower whole-body cardiopulmonary fitness and lower local skeletal muscle measures of oxygen utilisation and oxidative capacity but similar skeletal muscle microvascular function.