Tamariz et al. (2025)
- Authors: Leonardo Tamariz, Brian Garnet, Santiago Avecillas, Elizabeth Bast, Jeff Cournoyer, Nicole DeLuca, Nancy Klimas, Ana Palacio
- Institutes: Nova Southeastern University, Fort Lauderdale, FL, USA, Miami VA Healthcare System, Miami, FL, USA
- Publisher: Research Square
- Link: DOI
Summary
This study identifies a distinct metabolic signature in Long COVID patients, where the body relies on inefficient carbohydrate burning even at rest. This finding offers a biological explanation for post-exertional malaise and fatigue, moving the understanding of the condition beyond simple deconditioning. It suggests that metabolic inflexibility could be a valuable diagnostic marker for clinicians to identify the physiological roots of patient symptoms.
What was researched?
The study investigated whether abnormal energy metabolism and substrate utilization—specifically the preference for burning carbohydrates over fat—are linked to symptom severity in patients with Long COVID.
Why was it researched?
While fatigue and post-exertional malaise (PEM) are hallmark symptoms of Long COVID, standard exercise tests often show normal cardiovascular results, necessitating a look at metabolic efficiency at the cellular level.
How was it researched?
Researchers conducted a cross-sectional study of 50 Long COVID patients and 45 controls using cardiopulmonary exercise testing (CPET) on a cycle ergometer. Indirect calorimetry was used to calculate the respiratory exchange ratio (RER) to determine how much fat versus carbohydrate was used for energy at rest and during exertion.
What has been found?
The study found that 73% of Long COVID patients relied primarily on carbohydrates for energy at rest, compared to only 20% of healthy controls. Higher carbohydrate usage was significantly associated with severe fatigue and severe PEM, even though traditional metrics like peak oxygen uptake (VO2) were similar between groups.
Discussion
A major strength is the discovery of a metabolic pattern that correlates directly with patient-reported symptom severity like PEM. However, as a cross-sectional preprint, the study cannot yet confirm if this metabolic shift is the cause or a consequence of Long COVID, and larger longitudinal trials are needed.
Conclusion & Future Work
Long COVID patients exhibit inefficient energy consumption that serves as a metabolic signature of the disease. This pattern provides a potential diagnostic feature to better categorize and manage patients suffering from severe fatigue and PEM.