Cardiopulmonary Exercise Testing Provides Insights on Long-Haul COVID Symptoms

Female Athlete Performing ECG and VO2 test on Treadmill
Female athlete having a VO2 test with VO2 mask on face, electrocartiogram pads attached, treadmill.
Researchers investigated the cause of dyspnea in individuals with long-haul COVID and also screened the patients for myalgic encephalomyelitis/chronic fatigue syndrome.

Patients with post-acute sequelae of SARS-CoV-2 infection (PASC), informally referred to as “long-haul COVID,” were found to have circulatory impairment, abnormal ventilatory pattern, and/or myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), according to results of a prospective study published in JACC: Heart Failure.

For the analysis, researchers enrolled individuals (N=41) who developed dyspnea, or new and persistent shortness of breath, for over 3 months after recovering from a COVID-19 infection. Study participants received cardiopulmonary exercise testing (CPET) and were evaluated for ME/CFS symptoms.

The participants had a mean age of 45.2±12.5 years; 23 were women; 18 were men; body mass index (BMI) was 28.3±6.4; hemoglobin was 14.0±1.3 g/dL; 9 participants had hypertension; 4 had diabetes; 2 had postural orthostatic tachycardia; 1 had prior atrial fibrillation ablation; and 1 had a history of colon cancer.

The cohort had recovered from COVID-19 an average of 8.9±3.3 (range, 3-15) months previously. Nine had been hospitalized for their symptoms and received treatment, including azithromycin (n=5), steroids (n=5), hydroxychloroquine (n=4), convalescent plasma (n=2), remdesivir (n=2), enoxaparin (n=2), and apixaban (n=1). The non-hospitalized cohort received steroids (n=7) and azithromycin (n=3).

During the CPET, peak oxygen consumption was 77%±21% of the predicted value. Oxygen consumption less than 80% of predicted value was observed among 24 patients who had low oxygen consumption (n=12), low oxygen consumption pulse (n=22), and/or elevated slope of minute ventilation to carbon dioxide production (n=23). Patients (41%) who had oxygen consumption greater than or equal to 80% of predicted value were considered to have normal exercise capacity but with reduced oxygen consumption pulse (n=2), respiratory rate greater than 55 breaths/min (n=3), and/or abnormal ventilatory patterns (n=12).

Dysfunctional breathing was observed among 63% of study participants. The dysfunctional and normal breathers did not differ for oxygen consumption, resting end tidal pressure of carbon dioxide, maximum minute ventilation, respiratory rate, or respiratory exchange ratio.

Thirty-two patients met the 1994 diagnostic criteria for ME/CFS. Excluding patients with confounding comorbidities, 46% were considered to have ME/CFS. Nearly half of this cohort (42%) also had dysfunctional breathing.

This study was limited by its sample size and single center design, and results should be replicated in an independent cohort.

The study authors concluded that most patients with PASC had circulatory impairment with dysfunctional breathing and/or ME/CFS.

“Use of CPET may be effective in objectively identifying abnormalities associated with PASC that could be targeted for treatment,” the study authors noted.


Mancini DM, Brunjes DL, Lala A, Trivieri MG, Contreras JP, Natelson BH. Use of cardiopulmonary stress testing for patients with unexplained dyspnea post–coronavirus disease. JACC Heart Fail. Published online November 29, 2021. doi:10.1016/j.jchf.2021.10.002