Will There Be a Post-COVID-19 Form of ME/CFS?

By Anthony L. Komaroff, MD

Will some people who get COVID-19 subsequently develop ME/CFS? After all, many people with ME/CFS say that their illness began with some kind of infection: “a virus,” “a flu,” “a bad cold.” When it started, their illness didn’t feel that different from similar illnesses in the past, so no tests were done to determine what kind of infection it was. Their doctors thought there was no need, since these minor infections typically get better. Only this one didn’t get better, and the cause of the initial illness remained a mystery.

Other times, there is no mystery; the initial infection is clearly diagnosed. It might be infectious mononucleosis (“mono”), or it might be Lyme disease. The mystery then becomes why, after the clearly diagnosed illness has been treated, does the person remain sick for months and years thereafter?

Sometimes, people who develop ME/CFS—after what appears to be an infection—seem to have been part of a larger epidemic. That is, within a narrow window of time, large numbers of people in the same geographic area become sick with an illness that seems like an infection and then develop ME/CFS. Often these initial “infectious-like” illnesses are not severe, i.e. not that different from common infections. So doctors say, “it’s just something going around,” and don’t order tests. But the illness doesn’t get better.

Many such epidemics have been reported, all around the world, over the past 70 years. Organizations like the U.S. Centers for Disease Control and Prevention (CDC) have studied these apparent epidemics but often have been unable to find the cause of the initial infection. (1-3)

Other epidemics of more severe, clearly diagnosed infectious diseases—like SARS, (4) West Nile Virus, (5) dengue, (6) and Ebola virus (7)—can be followed by ME/CFS or a very similar illness.

So, there is abundant evidence that ME/CFS can follow either an apparently infectious illnesses of uncertain cause, or a clearly diagnosed infectious illness—including illnesses causes by viruses, bacteria, and even certain parasites.

Perhaps the best study of whether ME/CFS can develop following an infectious illness is a study supported by the CDC but conducted in a small, isolated, rural town in Australia, a town where people rarely leave to travel elsewhere. The town had one hospital, one laboratory, and a small group of doctors, making it easy to identify virtually every case of an infection that might lead to ME/CFS—and to follow people to see if they did develop ME/CFS. (8)

In this study, 253 individuals who developed an infection with either Epstein-Barr virus (a DNA virus), Coxiella burnetti (intracellular bacterium), or Ross River virus (an RNA virus) were followed for the next year. The study found that ME/CFS developed in 11% of the people. The strongest predictor of a “post-infective fatigue syndrome” was the severity of the initial illness, as judged both by symptoms and by laboratory test abnormalities. In other words, objective and measurable biological abnormalities predicted who would develop ME/CFS. In contrast, people with a past history of psychiatric illness were not more likely to develop ME/CFS.

It is therefore entirely plausible that some cases of ME/CFS will develop in people who get COVID-19. It is important to conduct studies that follow people with COVID-19 for several years, even after they recover, to see whether ME/CFS or other long-term complications will develop.

References

1. Shelokov, A., Habel, K., Verder, E. & Welsh, W. Epidemic neuromyasthenia: an outbreak of poliomyelitislike illness in student nurses. N Engl J Med 257, 345-355 (1957).

2. Poskanzer, D.C. et al. Epidemic neuromyasthenia: an outbreak in Punta Gorda, Florida. N Engl J Med 257, 356-364 (1957).

3. Acheson, E.D. The clinical syndrome variously called benign myalgic encephalomyelitis, Iceland disease and epidemic neuromyasthenia. Am J Med 4, 569-595 (1959).

4. Moldofsky, H. & Patcai, J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol 11, 37 (2011).

5. Sejvar, J.J. et al. Neurocognitive and functional outcomes in persons recovering from West Nile virus illness. J Neuropsychol 2, 477-99 (2008).

6. Seet, R.C., Quek, A.M. & Lim, E.C. Post-infectious fatigue syndrome in dengue infection. J Clin Virol 38, 1-6 (2007).

7. Epstein, L., Wong, K.K., Kallen, A.J. & Uyeki, T.M. Post-Ebola signs and symptoms in U.S. survivors. N Engl J Med 373, 2483-4 (2015).

8. Hickie, I. et al. Post-infective and chronic fatigue syndromes precipitated by viral and non-viral pathogens: prospective cohort study. BMJ 333, 575-8 (2006).