What the scan actually measures
Researchers scanning the brains of people with long COVID found something a standard blood panel would never catch: the cells themselves are running short on usable energy.
The tool is called phosphorus magnetic resonance spectroscopy, or 31P-MRS, and it does something a normal MRI cannot. Instead of imaging brain structure, it measures the chemical compounds that power every brain cell in real time, including adenosine triphosphate (ATP) and phosphocreatine (PCr).
The energy-buffering system behind every thought
ATP is the molecule cells burn for fuel. Phosphocreatine is the reserve tank: when ATP demand spikes, an enzyme called creatine kinase pulls a phosphate group off PCr and hands it to ADP to regenerate ATP almost instantly.
That reaction is why the ATP-to-phosphocreatine ratio matters as a biomarker. A lower ratio generally signals that cells are leaning harder on the phosphocreatine buffer relative to their steady-state ATP output, a pattern researchers associate with cellular energetic strain rather than a simple fuel shortage.
This is the same buffering system that creatine supplementation is designed to support in skeletal muscle, and it operates identically in neurons.
What the study found in post-COVID patients
The study, published in Biological Psychiatry in September 2026, used 31P-MRS to compare brain energy metabolism in people with neuropsychiatric post-COVID condition, the cluster of symptoms including brain fog, fatigue, depression, and cognitive slowing that can persist long after the initial infection clears.
The researchers found reduced ATP-to-phosphocreatine ratios in these patients relative to comparison groups, pointing to a measurable disruption in how brain cells generate and buffer energy. That finding lands this condition in the same neuroimaging territory as chronic fatigue syndrome and certain mood disorders, both of which have shown similar bioenergetic signatures on phosphorus spectroscopy in prior research.
Why the brain is especially vulnerable to an energy deficit
The brain makes up roughly 2% of body weight but consumes about 20% of the body’s resting energy budget, almost entirely to keep neurons firing and maintain ion gradients across cell membranes. Unlike muscle, neurons have almost no capacity to store fuel locally.
They depend on a constant, tightly regulated supply chain of ATP, and the phosphocreatine system is the first line of defense when that supply gets interrupted. A chronically strained buffer would help explain why post-COVID brain fog often behaves less like ordinary tiredness and more like a hard ceiling on mental stamina, one that worsens with cognitive exertion and doesn’t fully resolve with rest.
Mitochondrial dysfunction is the leading suspect
The mitochondria inside neurons are where most ATP gets produced, and a growing body of post-COVID research has pointed toward mitochondrial impairment as a downstream consequence of the initial viral infection. Persistent low-grade inflammation, microclotting in small vessels, and direct effects on mitochondrial enzymes have all been proposed as mechanisms.
A reduced ATP-to-phosphocreatine ratio on brain imaging doesn’t identify which of these mechanisms is driving the problem in any individual patient. It does provide an objective, measurable marker of the downstream effect, which matters in a condition that has historically been diagnosed almost entirely on self-reported symptoms.
Where creatine research fits into this picture
The study did not test creatine supplementation, and it would be a mistake to read it as evidence that creatine treats long COVID. But the mechanism it highlights, a strained phosphocreatine buffering system, is exactly the pathway that creatine research in other contexts has targeted.
Oral creatine raises the size of the muscle phosphocreatine pool, and separate lines of research have examined whether the same holds true in the brain, with some trials reporting modest cognitive benefits under conditions of sleep deprivation or mental fatigue. Whether boosting brain phosphocreatine stores could meaningfully help people with post-COVID energy deficits is an open question that this study doesn’t answer, but it is the logical next one.
What this means for patients right now
For the roughly one in ten COVID patients who go on to develop persistent symptoms, this kind of finding offers something that has been in short supply: a physiological marker that shows up on a scan rather than a symptom checklist. That distinction matters for a condition that has faced skepticism partly because standard blood tests and MRIs typically look normal.
It does not yet translate into a treatment, and 31P-MRS remains a specialized research tool rather than something available in routine clinical practice. What it does is give researchers a concrete biological target: a specific, measurable deficit in how the post-COVID brain generates and buffers its own fuel.
The bigger picture
Long COVID has spent years being described almost entirely in terms of symptoms nobody could quite pin down. A reduced ATP-to-phosphocreatine ratio doesn’t explain everything about why some people’s brains never fully recover from a COVID infection, but it reframes the question in terms biology can actually test.
The next studies to watch will be the ones that try to move the needle on that ratio, whether through pacing and rehabilitation, targeted anti-inflammatory approaches, or interventions aimed directly at the creatine kinase system that keeps every neuron’s lights on.
