Persistent Exertional Intolerance after COVID-19: Insights from Invasive Cardiopulmonary Exercise Testing.

Singh, Inderjit; Joseph, Phillip; Heerdt, Paul M.; Cullinan, Marjorie; Lutchmansingh, Denyse D.; Gulati, Mridu; Possick, Jennifer D.; Systrom, David M.; Waxman, Aaron B.

Background Some Coronavirus disease 2019 (COVID-19) patients who have recovered from their acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that is often unexplained by conventional investigative studies. Research question What is the patho-physiological mechanism of exercise intolerance that underlies the post-COVID-19 long haul syndrome following COVID-19 in patients without cardio-pulmonary disease? Study Design and Methods This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 post-COVID-19 patients without cardio-pulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results to 10 age- and sex matched controls. These data were then used to define potential reasons for exertional limitation in the post-COVID-19 cohort. Results Post-COVID-19 patients exhibited markedly reduced peak exercise aerobic capacity (VO2) compared to controls (70±11%predicted vs. 131±45%predicted; p<0.0001). This reduction in peak VO2 was associated with impaired systemic oxygen extraction (i.e., narrow CaVO2/CaO2) compared to controls (0.49±0.1 vs. 0.78±0.1, p<0.0001) despite a preserved peak cardiac index (7.8±3.1 vs. 8.4±2.3 L/min, p>0.05). Additionally, post-COVID-19 patients demonstrated greater ventilatory inefficiency (i.e., abnormal VE/VCO2 slope: 35±5 vs. 27±5, p=0.01) compared to controls without an increase in dead space ventilation. Interpretation Post-COVID-19 patients without cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a peripheral rather than a central cardiac limit along with an exaggerated hyper-ventilatory response during exercise.