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People with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) suffer from a chronic, debilitating fatigue that can leave them unable to maintain a job or take part in normal activities. Because of the condition’s unclear pathology and root causes, the disease was long dismissed as a psychiatric illness by doctors and ignored by researchers. Today, it’s estimated that 836,000 to 2.5 million Americans suffer from the disease—the vast majority of them undiagnosed—and that the illness costs billions annually in medical bills and lost incomes.
See “Could COVID-19 Trigger Chronic Disease in Some People?”
Below are the diagnostic criteria for the disease, according to the National Academy of Medicine.
 Debilitating fatigue | ME/CFS patients typically recall a sudden onset of a profound fatigue that lasts longer than six months and significantly reduces their ability to engage in normal activities. |
 Post-exertional malaise | The hallmark of the condition is a worsening of symptoms 12–48 hours after physical or mental activity, which can leave patients bedridden for days or weeks. |
 Unrefreshing sleep | Even a full night’s worth of sleep doesn’t improve symptoms, and patients often feel just as exhausted after waking up. |
 Cognitive problems | Many ME/CFS patients experience difficulties remembering things, processing new information, or concentrating. |
 Orthostatic intolerance | Some patients’ symptoms worsen after standing or sitting upright, exacerbating their fatigue and cognitive problems. |
Other symptoms | Some ME/CFS patients also report a racing heart, a sensitivity to light and sound, nausea, headaches, and muscle and joint pain. |
What causes ME/CFS?
Scientists still don’t know what causes ME/CFS, which has hampered efforts to develop treatments and diagnostic tests for the disease. However, there are several factors that appear to be involved.
 Viral infections | Many ME/CFS patients report having a viral infection prior to the onset of their symptoms, leading researchers to suspect that viruses could be involved in triggering the disease in some people. |
 Immune system | Based on findings of immune abnormalities in some ME/CFS patients, such as elevated levels of certain cytokines or poorly functioning immune cells, some researchers think the immune system may play a role in the disease’s pathology. |
 Energy and metabolism | Several studies have documented differences between ME/CFS patients and healthy controls in the way certain cells source their energy, which some researchers have suggested could explain the fatigue associated with the disease. |
 Nervous system | Investigations into ME/CFS patients’ brains and the autonomic nervous system—which controls functions such as body temperature, heart rate, and breathing rate—have revealed abnormalities in some patients. |
 Genetic factors | Observations from family and twin studies suggest that the risk for ME/CFS could be partly determined by genetics, but specific gene variants associated with the disease have remained elusive. |
Further Reading
Viral infections:
T. Pendergrast et al., “Housebound versus nonhousebound patients with myalgic encephalomyelitis and chronic fatigue syndrome,” Chronic Illn, 12:292–307, 2016.
Immune system:
A.H. Mandarano et al., “Myalgic encephalomyelitis/chronic fatigue syndrome patients exhibit altered T cell metabolism and cytokine associations,” J Clin Invest, 130:1491–505, 2020.
Energy and metabolism:
E. Sweetman et al., “A SWATH-MS analysis of myalgic encephalomyelitis/chronic fatigue syndrome peripheral blood mononuclear cell proteomes reveals mitochondrial dysfunction,” J Transl Med, 18:365, 2020.
Nervous system:
J.L. Newton et al., “Symptoms of autonomic dysfunction in chronic fatigue syndrome,” QJM: Int J Med, 100:519–26, 2007.
R.M. Escorihuela et al., “Reduced heart rate variability predicts fatigue severity in individuals with chronic fatigue syndrome/myalgic encephalomyelitis,” J Transl Med, 18:4, 2020.
Genetic factors:
D. Buchwald et al., “A twin study of chronic fatigue,” Psychosom Med, 63:936–43, 2001.
J.J. Dibble et al., “Genetic risk factors me ME/CFS: A critical review,” Hum Mol Genet, 29:R117–24, 2020.
