Reduced Exercise Tolerance in Long-COVID Patients

Introduction: Because many patients report long-term symptoms including dyspnea and fatigue after an acute COVID-19 infection, we recently developed a comprehensive follow-up clinic to understand and manage these patients. We conducted cardiopulmonary exercise tests (CPET) to characterize the respiratory responses to exercise as a potential cause of dyspnea in long-COVID patients. Methods: Seven long-COVID patients (mean age 53±4 years, 100% female) and seven age, sex and height-matched healthy controls (mean age 55±10 years) completed a pulmonary function test and an incremental CPET to exhaustion. These seven long-COVID patients were assessed due to persistent dyspnea after recovery from the acute infection;three long-COVID patients required hospitalization during the acute infection. The CPET was performed on average 158±59 days since COVID-19 diagnosis. Arterial saturation (SpO2) and breath-by-breath respiratory data, including ventilatory equivalents for carbon dioxide (VE/VCO2), were collected continuously, while inspiratory capacity (IC), inspiratory reserve volume (IRV), and dyspnea (modified Borg scale) were evaluated throughout exercise. Statistical analyses were performed using unpaired t-tests with a significance level of 0.05. Results: Prior to testing, COVID-19 patients reported resting dyspnea (mean modified Medical Research Council Dyspnea scale 2.1±0.7) and elevated post-COVID functional scale (mean 2.1±1.2), revealing persistent symptoms. Spirometric assessment at rest was within expected normal limits, though a reduction in FEV1 was seen in the COVID-19 patients (88.9±16.6% predicted) compared to matched controls (111.1±13.2% predicted;p = 0.02). Lung volumes and diffusion capacity were similar between both groups. Most notably, COVID-19 patients (19.6±7.4 mL/kg/min) had a reduced VO2peak when compared to controls (29.1±8.3 mL/kg/min, p<0.01). As well, VE/VCO2 at rest and anaerobic threshold were elevated in COVID-19 patients as compared to controls. SpO2 at peak exercise was not different between COVID-19 patients and controls (95±4% vs. 94±3%, p=0.57). At peak exercise, there were no between-group differences in tidal volume, breathing frequency, IC, IRV observed. Patient-reported dyspnea and leg fatigue at peak exercise were also similar between groups. Conclusion: Initial results suggest that long-COVID patients demonstrate reduced exercise tolerance and elevated VE/VCO2;however, SpO2, operating lung volumes and dyspnea responses to exercise are similar to healthy controls, suggesting that there may be a non-pulmonary cause for the observed exercise intolerance. Further investigation is required to understand this limitation and its relationship to symptoms in long-COVID patients.