Why Can’t Long COVID Patients Exercise Normally?

Their bodies struggle to extract and use oxygen efficiently. This study of 59 long COVID patients found O2 pulse at only 79% of predicted values, with 41% showing reduced exercise capacity and significant chronotropic intolerance (inability to reach normal heart rate). The findings point to impaired energy metabolism as a key mechanism.

Chronic fatigue, exercise intolerance, and post-exertional malaise are among the most debilitating symptoms of long COVID, affecting 10-20% of survivors. Researchers used gold-standard cardiopulmonary exercise testing (CPET) to understand why these patients struggle with physical activity.

What the Data Show

Patient Characteristics:

• 59 patients tested (34 men, 25 women), mean age 53.9 years
• Time since infection: Average 167 days (about 5.5 months)
• Hospitalization rate: 56% had been hospitalized with acute COVID
• ICU admission: 42% of hospitalized patients required ICU care
• Mechanical ventilation: 87% of ICU patients needed ventilators

Oxygen Extraction and Energy Metabolism:

• O2 pulse peak: 79% ± 12.9% of predicted (significantly reduced)
• Mean VO2 peak: 89.2% ± 22.2% of predicted
• Reduced exercise capacity: 41% of patients (VO2 peak ≤84% predicted)
• Test duration: Only 79.6% of predicted

Heart Rate Response (Chronotropic Intolerance):

• Mean HR peak % predicted: ≤75% in the full cohort
• Non-ICU patients with maximal tests: HR peak only 69% ± 7.7% predicted
• Patients with normal VO2 capacity: Still showed HR peak of only 65.5% (should reach 80%+)
• Diagnosis: Chronotropic intolerance confirmed in those unable to reach 80% of age-predicted HR max

Pulmonary Function:

• FVC: Only 74% predicted (range 64-90%)
• FEV1: 82.2% predicted
• Breathing inefficiency: 30.5% showed high VE/VCO2 slope (≥34)

Differences by Exercise Capacity:

Dr. Kumar’s Take

This is important research that validates what long COVID patients experience. The data show their exercise intolerance has real, measurable physiological causes.

The O2 pulse finding is particularly significant. O2 pulse reflects both cardiac output (stroke volume) and how well tissues extract oxygen from blood. At 79% of predicted, these patients’ bodies simply aren’t producing energy efficiently during exercise.

The chronotropic intolerance finding is equally striking. Even patients with “normal” oxygen consumption still showed blunted heart rate responses (65.5% versus the expected 80%+). This indicates autonomic nervous system dysfunction affecting how the heart responds to exercise demands.

I find it telling that the researchers specifically recommend therapies that “optimize bioenergetics and improve oxygen utilization.” Oxygen-enhanced exercise protocols may be particularly relevant for this population.

Why Energy Metabolism Fails in Long COVID

The researchers hypothesize multiple contributing factors:

Impaired Mitochondrial Function: Mitochondria are the cell’s energy factories. Post-COVID damage may impair their ability to produce ATP, leaving muscles unable to sustain exercise.

Poor Oxygen Conductance: Even with adequate blood flow, oxygen may not move efficiently from blood to muscle cells. This creates an energy bottleneck at the tissue level.

Autonomic Dysfunction: The blunted heart rate response indicates the nervous system isn’t properly regulating cardiovascular responses to exercise. This affects blood flow distribution and exercise tolerance.

Ventilatory Inefficiency: Nearly a third of patients showed breathing inefficiency (high VE/VCO2 slope), meaning they needed to breathe more to achieve the same oxygen uptake.

Post-Exertional Malaise Connection

Post-exertional malaise (PEM) is defined as “inappropriate loss of physical and mental stamina, rapid muscular and cognitive fatigability” after activity. Symptoms can be immediate or delayed 24-72 hours.

The researchers note their findings mirror patterns seen in ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome), suggesting similar underlying mechanisms of impaired energy metabolism.

Gender Differences

Women with reduced exercise capacity:

• Higher VE/VCO2 slope (38.8) suggesting hyperventilation
• Lower RER peak (1.0 vs 1.1) indicating submaximal effort

Men with reduced exercise capacity:

• Worse pulmonary function values (FVC, FEV1, PEF)
• May indicate more severe COVID-19 disease or preexisting conditions

Study Limitations

The researchers acknowledge:

• No data on comorbid conditions or symptom severity
• Timing of CPET varied widely (days post-diagnosis)
• DLCO (lung diffusion capacity) wasn’t measured
• Heterogeneous sample (ICU and mild COVID together)
• Single CPET may overestimate capacity in patients with PEM

They recommend 2-day CPET protocols to assess whether patients can reproduce their performance 24 hours later.

Practical Takeaways

• Long COVID exercise intolerance has measurable physiological causes
• O2 pulse and chronotropic intolerance are key biomarkers
• Impaired oxygen extraction and energy metabolism drive symptoms
• Therapies targeting bioenergetics and oxygen utilization may help
• Sub-symptom, low-intensity aerobic exercise may provide therapeutic stimulus
• Exercise improves nitric oxide, which has vasodilator and antiviral effects
• Supervised, graduated exercise programs should be individualized

Related Studies and Research

• Supplemental Oxygen and Muscle Metabolism in Mitochondrial Myopathy
• Hyperbaric Oxygen Therapy on Long COVID: Systematic Review
• Effect of Physical Exercise-based Rehabilitation on Long COVID
• Hyperbaric Oxygen Addresses Pathophysiology of Long COVID

FAQs

What is O2 pulse and why does it matter?

O2 pulse measures oxygen consumed per heartbeat. It equals stroke volume multiplied by arterial-venous oxygen difference. In this study, O2 pulse of 79% predicted indicates that either the heart isn’t pumping efficiently, tissues aren’t extracting oxygen well, or both. This explains why patients fatigue quickly during activity.

What is chronotropic intolerance?

Chronotropic intolerance means the heart rate doesn’t rise appropriately during exercise. Diagnosis requires inability to reach 80% of age-predicted maximum heart rate during maximal exercise testing. In this study, even patients with “normal” exercise capacity showed HR peaks of only 65.5% predicted, indicating widespread autonomic dysfunction.

Does exercise make long COVID worse?

It can for some patients. Post-exertional malaise causes symptom worsening after activity, sometimes delayed 24-72 hours. Any exercise program should be sub-symptom threshold, meaning intensity should stay below the level that triggers symptoms. The researchers suggest low-intensity aerobic exercise may help by improving mitochondrial function and nitric oxide production.

Could oxygen therapy help these patients?

The study’s conclusions specifically support “therapies that optimize bioenergetics and improve oxygen utilization.” Given the impaired O2 pulse and oxygen extraction findings, supplemental oxygen during exercise rehabilitation could theoretically address the oxygen delivery bottleneck these patients experience.

Bottom Line

This study of 59 long COVID patients reveals specific physiological mechanisms behind exercise intolerance. With O2 pulse at only 79% of predicted and chronotropic intolerance affecting most patients, the data demonstrate impaired oxygen extraction and autonomic dysfunction. The 41% rate of reduced exercise capacity and blunted heart rate responses explain why these patients struggle with activity. The findings support therapies targeting bioenergetics and oxygen utilization, while emphasizing that careful, sub-symptom exercise may help improve mitochondrial function and overall oxygen metabolism.

Read the full study