Chronic Illness Research7 min read7 September 2026

Long COVID and ME/CFS: what these studies can tell us

Promising questions, small studies and the distance between a finding and a treatment.

A blood test tells us about what it measured. It cannot answer every question about a changing illness. These studies explore several possible mechanisms; their findings need to be read with their sample sizes, methods and limits in view.

What is going on

One Genomic Signature Runs Under Five Diagnoses

ME/CFS, long COVID, PTSD, rheumatoid arthritis and multiple sclerosis look unrelated on a chart. Underneath, several of them share the same regulatory wiring.

Researchers led by Ewan Hunter used a 3D genomics platform called EpiSwitch, which maps how DNA physically folds so that distant regions of the genome can contact each other and switch nearby genes on or off, to compare genetic data across ME/CFS, long COVID, PTSD, rheumatoid arthritis and multiple sclerosis. The five conditions share almost none of the same individual genes. What they do share is a set of regulatory pathways: cytokine signalling (the immune system's chemical messaging), the interferon response that usually handles viral infections, and mitochondrial function, the cell's energy-producing machinery.

→Five separate diagnoses may be running through some of the same regulatory circuitry, not five unrelated coincidences.

A Named Virus Behind the Worst Outcomes

COVID does not just infect. In a large hospitalised cohort, it woke up eleven other viruses that were already lying dormant in the body.

A team led by Jessica Maguire at Boston Children's Hospital tracked 1,154 hospitalised COVID-19 patients across 20 US research hospitals and found eleven latent viruses reactivating within the first 40 days, most often Epstein-Barr virus, herpes simplex virus 1, cytomegalovirus and a virus family called Anelloviridae that most adults carry without ever noticing. Anelloviridae reactivation specifically tracked with long-term physical disability and long COVID. The mechanism looked unexpected too: Epstein-Barr and cytomegalovirus seemed to reactivate in response to inflammation itself, not because the immune system had been suppressed, which is the explanation doctors had reached for until now.

→The original infection may not be the only thing still active in the body. Something it woke up could be.

Testing a possible prevention approach

Trials have investigated metformin during acute COVID-19. Their outcomes and limitations need careful interpretation.

The ACTIV-6 trial investigated metformin during acute COVID-19 and outcomes six months later. This is research about a prescribed medicine in a defined trial population, not evidence for treating established long COVID with Coji or for starting medication yourself. Discuss treatment questions with a clinician.

→Prevention studies and studies treating an established condition answer different questions.

POTS Has Its Own Immune Signature

Not every case of a racing heart and crashing blood pressure after long COVID looks the same under the microscope. One subtype has a specific immune fingerprint.

Postural orthostatic tachycardia syndrome, or POTS, is a type of dysautonomia (a nervous system that struggles to automatically regulate things like heart rate and blood pressure) that causes heart rate to spike and blood pressure to swing when standing up. A 2026 study of 106 long COVID patients found that people meeting POTS criteria carried a distinct immune signature: a strong cellular immune response to the coronavirus spike protein, alongside raised IgG antibodies (the long-lasting kind the body produces after an infection) against the virus's nucleocapsid protein, a structural protein separate from the spike. That signature set them apart from other long COVID patients with cardiovascular dysautonomia and from those with neither. General inflammatory markers and common autoantibodies showed no such link, meaning the standard bloodwork most patients are offered would not have caught this signature at all.

→A negative general antibody panel does not rule out an immune cause. It may just mean the wrong antibody was tested.

What a small imaging study found

Long COVID brain fog was widely assumed to mean brain-wide inflammation. New imaging says the picture is more specific, and more useful, than that.

A small University of Turku imaging study included 14 people with long COVID. It found no overall increase in its measures of brain inflammation compared with healthy controls, while some regional signals were associated with symptoms. It did not locate a single cause of brain fog.

→This study leaves the causes of persistent cognitive symptoms open. Larger studies are needed.

What this could mean in practice

So what helps?

These studies leave questions open. A symptom record and a discussion with a clinician can help connect research to your own circumstances.

These studies ask different questions about long COVID and ME/CFS. Findings about genes, viruses and brain imaging are not interchangeable, and none can establish what is happening in a particular reader. Discuss clinical questions with a professional who knows your history.

"The right test for this may not have been run yet"

Metformin taken early in an acute COVID infection now has trial-level evidence behind it as prevention, worth raising with a GP ahead of a future infection rather than only after symptoms set in.

Shared regulatory pathways across five conditions point toward blood-based biomarkers eventually replacing today's diagnosis-by-elimination process, where every other explanation has to be ruled out first.

A neuroinflammation signal specific to certain brain regions, rather than the whole brain, may explain why some brain fog eases with time while a normal-looking scan does not.

Bring questions about a study to a clinician who knows your circumstances. A research finding and an available treatment are different things.

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