Persistent Exertional Intolerance After COVID-19 Insights From Invasive Cardiopulmonary Exercise Testing

BACKGROUND: Some patients with COVID-19 who have recovered from the acute infection after experiencing only mild symptoms continue to exhibit persistent exertional limitation that often is unexplained by conventional investigative studies. RESEARCH QUESTION: What is the pathophysiologic mechanism of exercise intolerance that underlies the post-COVID-19 long-haul syndrome in patients without cardiopulmonary disease? STUDY DESIGN AND METHODS: This study examined the systemic and pulmonary hemodynamics, ventilation, and gas exchange in 10 patients who recovered from COVID-19 and were without cardiopulmonary disease during invasive cardiopulmonary exercise testing (iCPET) and compared the results with those from 10 age- and sex-matched control participants. These data then were used to define potential reasons for exertional limitation in the cohort of patients who had recovered from COVID-19. RESULTS: The patients who had recovered from COVID-19 exhibited markedly reduced peak exercise aerobic capacity (oxygen consumption [VO2]) compared with control participants (70 +/- 11% predicted vs 131 +/- 45% predicted; P < .0001). This reduction in peak VO(2 )was associated with impaired systemic oxygen extraction (ie, narrow arterial-mixed venous oxygen content difference to arterial oxygen content ratio) compared with control participants (0.49 +/- 0.1 vs 0.78 +/- 0.1; P < .0001), despite a preserved peak cardiac index (7.8 +/- 3.1 L/min vs 8.4 +/- 2.3 L/min; P > .05). Additionally, patients who had recovered from COVID-19 demonstrated greater ventilatory inefficiency (ie, abnormal ventilatory efficiency [VE/VCO2] slope: 35 +/- 5 vs 27 +/- 5; P = .01) compared with control participants without an increase in dead space ventilation. INTERPRETATION: Patients who have recovered from COVID-19 without cardiopulmonary disease demonstrate a marked reduction in peak VO2 from a peripheral rather than a central cardiac limit, along with an exaggerated hyperventilatory response during exercise.