Insights from ME/CFS research that illuminate long COVID


Sarah Annesley, Daniel Missailidis, Benjamin Heng, Elisha K Josef, Christopher W Armstrong


La Trobe University, Macquarie University, Murdoch Children’s Research Institute, University of Melbourne, Mercy Hospital for Women, Australia


Trends in Molecular Medicine, 2024 May; 30(5):443–58


Sarah Annesley and Daniel Missailidis were supported by ME Research UK with the financial support of The Fred and Joan Davies Bequest

Key findings

ME/CFS and long COVID share many of the same symptoms, and around half of patients with long COVID fulfil diagnostic criteria for ME/CFS.

It is not know how either condition progresses into a chronic disease, but a number of pathological mechanisms have been proposed, and many of these are also shared between ME/CFS and long COVID.

Drawing from a review of recent research findings, this article highlights some of the pathological changes that are similar in people with ME/CFS and those with long COVID, and discusses how research in one condition may provide insights into the other.

Dysfunction of the immune system has frequently been reported in both ME/CFS and long COVID, including the production of autoantibodies (immune cells which can attack healthy cells), impaired immune responses, and the possibility of viral persistence and reactivation.

Abnormalities in metabolism have also been reported in both diseases, including a greater reliance in using alternatives to carbohydrates in the production of energy, and an increase in damaging reactive oxygen species in muscle and white blood cells.

The gut microbiota (comprising resident bacteria essential for health) have been assessed in both ME/CFS and long COVID, and a common finding in both conditions is a reduction in bacteria that produce butyrate, a substance which has several important roles in the gut.

Multiple neurological symptoms in both conditions (such as cognitive difficulties, sleep problems and autonomic dysfunction) point to the involvement of the central nervous system. Potential mechanisms include neuroinflammation, altered brain volume and connectivity, and reduced cerebral blood flow.

Finally, ME/CFS can be associated with several abnormalities in the cardiovascular system, including abnormalities in heart function, dysfunction of the vascular endothelium (which controls blood vessels), and defects in blood clotting. Patients with long COVID also have an increased risk of developing many of these cardiovascular problems.

The authors conclude by suggesting that “long COVID may represent a unique opportunity to study early disease changes and map these changes over the duration of the disease”, while ME/CFS research (where patients often have a longer disease duration) “may provide clues as to the future disease pathology of long COVID”.

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