Long COVID and Chronic Fatigue Share Same Genetic Root

A team of scientists at the University of East Anglia, working with the company Oxford BioDynamics, published a paper on September 2, 2026, that links five seemingly unrelated illnesses through one shared biological network behind chronic fatigue. The diseases are myalgic encephalomyelitis, better known as chronic fatigue syndrome, long COVID, post-traumatic stress disorder, rheumatoid arthritis and multiple sclerosis. The peer-reviewed paper appeared in the Journal of Translational Medicine, led by Professor Dmitri Pshezhetski of the Norwich Medical School, part of the University of East Anglia. Researchers from Oxford BioDynamics, the London School of Hygiene and Tropical Medicine and the Cornwall Partnership NHS Foundation Trust also worked on the study.

This is not the first time the same platform has produced a result in this field. Earlier work using the EpiSwitch technology already led to a blood test for chronic fatigue syndrome, which showed strong diagnostic accuracy and is awaiting further validation before clinical use. The new analysis builds on that work, now extended to four additional diseases that share similar symptoms but have until now been treated as entirely separate conditions.

Rather than reading the sequence of letters in DNA, the way most genetic studies do, the researchers used the EpiSwitch Orion platform, which tracks the genome’s three dimensional architecture: how the DNA strand folds and touches itself inside the cell. The analysis was entirely computational. The team combined previously published genome-wide association data for long COVID, PTSD, rheumatoid arthritis and multiple sclerosis with three dimensional genomic data from an earlier study of chronic fatigue syndrome patients. No new samples were taken from patients, so the findings rest solely on reprocessing data that already existed.

At the level of individual genes, the overlap between the five diseases was small, almost negligible. When the researchers instead mapped the networks of interactions between those genes, a very different picture emerged. The systems affected across all five conditions include immune signaling, inflammatory pathways, mitochondrial energy production, metabolic regulation, stress response and neuroendocrine signaling, the mechanisms that govern how the body manages energy and immunity. Among the hub genes the analysis singled out was LAG3, a molecule tied to what is known as T cell exhaustion, a state in which immune cells simply stop functioning efficiently after prolonged activation.

“At the level of individual genes, there was surprisingly little direct overlap between long COVID, chronic fatigue syndrome, post-traumatic stress disorder, multiple sclerosis and rheumatoid arthritis. But when we looked at how those genes interact within complex biological networks, a completely different picture emerged,” Professor Pshezhetski said in a statement from the University of East Anglia.

The team’s conclusion is that different triggers, whether a viral infection, psychological trauma or an autoimmune response, can ultimately converge on the same deep exhaustion, because they affect the same regulatory networks in the body. If confirmed, that could open the door to objective blood tests and, eventually, treatments that act on several chronic diseases at once rather than treating each one separately.

Even so, this is a preliminary finding that calls for caution. The analysis was purely computational, built on previously published data, without new patient samples or clinical testing of the mechanisms it proposes. The hub genes it identified, LAG3 included, are candidates the study flagged, not confirmed causes, and the authors themselves say further research is needed to establish what role they actually play. The study shows that five diseases share connected biological networks, not that they are the same disease, and not that a single mechanism causes all of them.