Mitochondria, Meaning, and the Long Goodbye of Viral Illness
Long after the fever breaks and the test turns negative, many people discover that something essential never came back online. The body is present. The labs look acceptable. The doctors are polite. And yet energy – real energy, the kind that lets you think clearly, walk uphill, or feel joy without planning it – remains stubbornly unavailable.
This is the strange aftermath of post-viral illness, now most visible under the banner of Long COVID but familiar to clinicians who have followed patients through Epstein–Barr, Lyme, influenza, and other infections that refuse to leave quietly. These syndromes are not defined by a single symptom but by a shared absence of vitality without explanation.
A growing body of research now suggests that this experience is not vague, psychological, or mysterious. As summarized in a recent comprehensive review published in Biomolecules (MDPI), “Mitochondrial Reactive Oxygen Species: A Unifying Mechanism in Long COVID and Spike Protein-Associated Injury: A Narrative Review“, post-viral syndromes can be understood as disorders of cellular energy metabolism, with mitochondria at the center of the story.
The emerging science suggests a surprisingly mundane culprit. The power is still on, but the generators are damaged.
Mitochondria are More Than Power Plants, Less Than Gods
Mitochondria are usually introduced as cellular power plants, a phrase that does them a mild disservice. They are not factories so much as translators, taking oxygen, nutrients, stress signals, and immune cues, and converting them into decisions about survival, inflammation, repair, or retreat.
Viruses know this. As outlined in the MDPI review, many viral proteins directly interact with mitochondrial membranes, electron transport chains, and intracellular signaling pathways. During acute infection, this sabotage may be strategic. The virus needs the cell alive, but distracted. Energy is rerouted. Reactive oxygen species rise. Immune alarms sound.
Normally, when the infection resolves, damaged mitochondria are cleared out like broken furniture after a house fire. Mitophagy – the cellular cleanup crew – removes the wreckage. New mitochondria are built – biogenesis. Balance returns.
In post-viral illness, that cleanup never quite finishes. The MDPI authors emphasize impaired mitophagy and persistent mitochondrial injury as key features of Long COVID and related syndromes. Instead of being recycled, dysfunctional mitochondria accumulate, leaking oxidative signals and confusing the immune system. The result is not dramatic inflammation but a low-grade metabolic stalemate. Cells remain alive, but underpowered. The lights flicker. The body adapts downward.
Oxidative Stress is When Signaling Becomes Noise
Reactive oxygen species are not villains by default. In healthy physiology, they function like punctuation marks – brief, meaningful signals that help cells adapt. Trouble begins when punctuation becomes static.
The MDPI review highlights mitochondrial reactive oxygen species (mtROS) as a unifying mechanism behind persistent post-viral symptoms. Excessive mtROS disrupts electron transport, damages membranes, and perpetuates immune activation. Over time, this oxidative hum becomes the background noise of daily life: fatigue that sleep cannot fix, brains that feel wrapped in cotton, muscles that protest mild exertion as if it were betrayal.
This framework explains why post-viral illness feels qualitatively different from ordinary fatigue, burnout, or depression. The problem is not motivation or mood, it’s chemistry.
Redox Repair for Giving Cells a Fighting Chance
If oxidative stress is part of the problem, restoring redox balance becomes a logical starting point. The MDPI authors discuss redox dysregulation not as a side effect, but as a central driver of ongoing pathology.
Antioxidant support in this context is not about megadoses or magical thinking. It is about reducing unnecessary molecular friction so mitochondria can function without constantly fighting fires.
Coenzyme Q10 supports electron transport directly, improving efficiency where energy is actually made. Alpha-lipoic acid works both as an antioxidant and as a metabolic facilitator, helping recycle other antioxidants while supporting mitochondrial enzymes. Vitamins C and E provide broad redox buffering, while polyphenols influence signaling pathways involved in mitochondrial renewal and biogenesis.
None of these nutrients are cures. They are scaffolding – temporary supports that allow damaged systems to stabilize while deeper repair unfolds.
NAD⁺ The Cellular Currency of Resilience
If mitochondria are generators, NAD⁺ is the currency they trade in. Every meaningful energy transaction in the cell depends on it. NAD⁺ fuels ATP production, regulates sirtuin activity, supports DNA repair, and governs how cells respond to metabolic stress.
The MDPI review situates NAD⁺ depletion squarely within the biology of post-viral illness. Infection-driven inflammation, oxidative stress, and immune activation accelerate NAD⁺ consumption, leaving cells energy-poor and metabolically inflexible.
Restoring NAD⁺ availability is therefore less about stimulation and more about permission – permission for cells to do what they already know how to do.
Oral NAD⁺ precursors such as nicotinamide riboside and NMN provide raw materials the body can use to rebuild intracellular pools. Experimental and early human studies suggest these compounds improve mitochondrial efficiency and reduce oxidative stress. Clinically, they often work slowly and quietly, which is exactly how foundational repair tends to happen.
IV NAD Therapy: The Elevator Instead of the Stairs
Intravenous NAD therapy takes a different approach. Instead of encouraging the body to rebuild NAD⁺ gradually, it attempts to deliver it directly, like carrying fuel straight to the generator room. We often observe significant healing and energy return with a series of NAD infusions.
Although IV NAD therapy is not yet addressed directly in the MDPI review, the paper’s emphasis on NAD⁺ depletion and mitochondrial bioenergetics provides a clear mechanistic rationale for why such an approach might help some patients.
Patients often report transient improvements – clearer thinking, increased energy, a sense that the fog has lifted just enough to remember what normal felt like. For some, this is motivating. For others, the effect fades as quickly as it arrived.
The science here is still catching up to the enthusiasm. Robust clinical trials are limited, and oral precursors may achieve similar intracellular effects over time. IV NAD can be uncomfortable if infused too quickly and is costly enough to demand discernment rather than devotion.
Used thoughtfully, IV NAD may function as a metabolic jump-start rather than a solution. It can create a window – a brief reminder to the system that energy production is still possible – while longer-term strategies take root.
Lifestyle Is Not Optional Biology
No mitochondrial therapy works in a vacuum. Movement, nutrition, sleep, and stress are not “supportive care.” They are signals.
The MDPI authors underscore that mitochondrial health is exquisitely sensitive to environmental and behavioral inputs. Gentle, well-timed exercise tells mitochondria they are still needed. Excessive exertion tells them to shut down. Sleep synchronizes repair cycles that mitochondria depend on. Nutrition supplies not just calories but information – polyphenols, micronutrients, fatty acids – that shape metabolic behavior. Chronic stress, meanwhile, acts like a background toxin, quietly impairing mitochondrial function through hormonal and inflammatory pathways.
Recovery happens when these signals stop contradicting each other.
A Different Kind of Medicine
Post-viral illness forces medicine to confront an uncomfortable truth. Many of our best tools are designed to suppress, block, or destroy. Mitochondria require something else. They require support and cooperation.
The MDPI review reframes Long COVID and related syndromes not as lingering infections, but as mitochondrial and redox disorders – a shift that helps explain both the persistence of symptoms and the failure of purely symptomatic treatments.
This is slower medicine. Quieter medicine. Functional medicine. The kind that rarely makes headlines but occasionally restores a life.
Author
Scott Rollins, MD, is Board Certified with the American Board of Family Practice and the American Board of Anti-Aging and Regenerative Medicine. He specializes in bioidentical hormone replacement for men and women, thyroid and adrenal disorders, fibromyalgia and other complex medical conditions. He is founder and medical director of the Integrative Medicine Center of Western Colorado (www.imcwc.com) and Bellezza Laser Aesthetics (www.bellezzalaser.com). Call (970) 245-6911 for an appointment or more information.
