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

Chest. 2022 Jan;161(1):54-63. doi: 10.1016/j.chest.2021.08.010. Epub 2021 Aug 11.


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 VO2 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.

Keywords: COVID-19; cardiopulmonary exercise test; hemodynamics; iCPET; long haulers; post-COVID-19 syndrome.

MeSH terms

  • COVID-19 / complications*
  • COVID-19 / physiopathology
  • Connecticut
  • Exercise Test / methods*
  • Exercise Tolerance*
  • Female
  • Hemodynamics / physiology
  • Humans
  • Male
  • Massachusetts
  • Middle Aged
  • Oxygen Consumption / physiology
  • Post-Acute COVID-19 Syndrome
  • Respiratory Function Tests
  • SARS-CoV-2
  • Stroke Volume / physiology