PATIENT RESOURCE
Long COVID & Mitochondrial Dysfunction
Written by Ayla Wolf, DAOMDoctor of Acupuncture and Oriental Medicine with advanced training in applied clinical neuroscience.
Read Dr. Wolf’s full bio →Why fatigue, brain fog, and exercise intolerance may persist — and what may help.
Long COVID can affect nearly every system in the body. While symptoms vary widely, fatigue, brain fog, muscle pain, weakness, and shortness of breath are among the most common — and they often worsen after physical or mental exertion.
One possible contributor receiving increasing attention is mitochondrial dysfunction. Mitochondria convert nutrients and oxygen into ATP — the form of energy cells can readily use. They also help regulate inflammation, oxidative stress, immune signaling, and cellular repair. Research suggests that SARS-CoV-2 may disrupt mitochondrial function in some people, which may help explain why many long-COVID symptoms appear together.
How Mitochondrial Dysfunction May Show Up in Long COVID
Persistent fatigue and post-exertional symptom worsening
When cells cannot produce or restore energy efficiently, even ordinary activities may require a disproportionate amount of effort. Some people experience post-exertional symptom exacerbation (PESE) — symptoms may intensify hours or even a day or two after physical, cognitive, or emotional exertion and can remain worse for days or weeks. This is more than ordinary tiredness and should not be approached by simply pushing through it.
Brain fog and memory difficulties
The brain uses a tremendous amount of energy. When energy metabolism is disrupted — combined with inflammation, altered blood flow, poor sleep, or autonomic dysfunction — attention, processing speed, word retrieval, and memory may suffer. People often describe losing their train of thought, struggling to find words, or needing much more effort to complete tasks that once felt automatic.
Muscle pain, weakness, and reduced endurance
Skeletal muscles rely heavily on mitochondria to sustain activity and recover afterward. Disrupted energy production and increased oxidative stress may contribute to muscle aching, weakness, heaviness, and prolonged recovery after exertion. Inflammation, altered pain processing, deconditioning, neuropathy, and circulatory or autonomic changes may also be involved.
Shortness of breath and exercise intolerance
Breathlessness after COVID can have many possible causes, including residual lung or heart problems, autonomic dysfunction, dysfunctional breathing patterns, impaired oxygen extraction, and deconditioning. New, severe, or worsening breathing difficulty, chest pain, fainting, or low oxygen levels requires medical evaluation.
Strategies That May Support Recovery
Mitochondrial support should not become a one-size-fits-all protocol. The first step is identifying which mechanisms and symptoms appear most relevant for each person and ruling out problems that need conventional medical care. Depending on the individual, the following strategies may be considered as part of a broader, personalized plan.
Creatine: Supporting the Cell's Energy-Buffering System
Creatine is best known as a sports supplement, but its role extends beyond muscle building. The body converts creatine into phosphocreatine, which acts as a rapidly available energy reserve. A 2026 pilot trial of 67 adults with long-COVID fatigue found that the 6-gram group showed a greater reduction in fatigue and an improvement in handgrip strength compared with placebo. Creatine monohydrate is the most extensively studied form; many people take 3–5 grams per day. Anyone with kidney disease, pregnancy, or significant medical conditions should discuss supplementation with a healthcare professional first.
CoQ10: Important Biology, Mixed Clinical Evidence
Coenzyme Q10 is an essential component of the mitochondrial electron transport chain and functions as an antioxidant. However, a randomized phase 2 crossover trial found that high-dose CoQ10 did not significantly reduce the number or severity of long-COVID symptoms compared with placebo. CoQ10 may still be considered in selected situations, but expectations should be realistic.
Chinese Herbal Medicine: Individualized, Symptom-Focused Care
Chinese herbal medicine offers a highly individualized approach. Rather than giving every person with long COVID the same formula, treatment is based on the person's overall pattern of symptoms, constitution, digestion, sleep, temperature regulation, pain, and respiratory function. Herbal medicine should be prescribed by a properly trained practitioner who can screen for herb–drug interactions and contraindications.
Red & Near-Infrared Light Therapy (Photobiomodulation)
Red light therapy uses specific wavelengths of light to influence cellular activity. One proposed mechanism involves cytochrome c oxidase, an enzyme in the mitochondrial electron transport chain. Small clinical trials have reported encouraging findings for selected symptoms, including persistent changes in smell and taste and cognitive dysfunction. Research in long COVID is still developing, and treatment protocols vary considerably. A device should be selected and used with guidance from a clinician familiar with photobiomodulation.
Pacing: An Essential Foundation
Supplements and therapies are only one part of the picture. For people who experience delayed symptom worsening after exertion, respecting the body's current energy limits is essential. Pacing means balancing activity and recovery to reduce crashes — breaking tasks into smaller pieces, alternating physical and cognitive demands, building in rest before symptoms spike, and tracking delayed responses to activity. Exercise may help some people with long COVID, but it needs to be symptom-titrated.
A More Complete Approach to Long-COVID Recovery
Mitochondrial dysfunction offers a compelling lens through which to understand fatigue, cognitive changes, pain, weakness, and exercise intolerance after COVID. But it is one piece of a much larger puzzle. The most effective care begins with a thorough evaluation, attention to the person's dominant symptom pattern, and a plan that can change as the nervous system, immune system, circulation, and energy metabolism recover.
The encouraging news is that research into long COVID and cellular energy metabolism is rapidly expanding. As we learn more, mitochondrial support may become an increasingly precise part of helping people rebuild function, reduce symptoms, and regain more of their lives.
View References
- Al-Aly, Z., Topol, E. J., et al. (2024). Long COVID science, research and policy. Nature Medicine, 30, 2148–2164.
- Molnar, T., et al. (2024). Mitochondrial dysfunction in long COVID. Clinical Chimica Acta, 558, 117892.
- Macnaughtan, J., et al. (2025). Mitochondrial function is impaired in long COVID patients.
- Ostojic, J., et al. (2024). Decreased cerebral creatine after severe COVID-19. Journal of Clinical Medicine, 13(14), 4128.
- Slankamenac, J., et al. (2023). Effects of six-month creatine supplementation in post-COVID-19 fatigue syndrome. Food Science & Nutrition, 11(11), 6899–6906.
- Santos, M. S. C., et al. (2026). Creatine supplementation on fatigue related to post-COVID-19 condition. Frontiers in Nutrition, 13, 1731306.
- Naeini, E. K., et al. (2025). Effect of creatine supplementation on kidney function: A systematic review.
- Lim, L., et al. (2026). Photobiomodulation for cognitive dysfunction in post-COVID-19 condition. EClinicalMedicine.
- Telles-Araujo, G. T., et al. (2025). Photobiomodulation for persistent olfactory and gustatory dysfunction post-COVID-19. Lasers in Medical Science, 40, 283.
- Hansen, K. S., et al. (2023). High-dose CoQ10 versus placebo in post COVID-19 condition. The Lancet Regional Health – Europe, 24, 100539.
- World Health Organization. Post COVID-19 condition: Clinical management and rehabilitation guidance.
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Schedule a Consultation →Key Takeaways
- ✓Mitochondrial dysfunction may contribute to fatigue, brain fog, pain, and exercise intolerance in long COVID
- ✓Post-exertional symptom worsening (PESE) is real — pushing through it often makes things worse
- ✓Creatine (3–6g/day) shows promising early evidence for long-COVID fatigue
- ✓Red light therapy is being studied for brain fog and smell/taste changes
- ✓Pacing is an essential energy-management strategy
- ✓Individualized care outperforms one-size-fits-all protocols
Strategies Discussed
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