About 1 in 22 people who survive COVID-19 go on to develop a typically lifelong disease called myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), new research suggests.
Previous research has shown that ME/CFS can be triggered by viral and bacterial infections, such as Epstein-Barr virus, which causes mono, and Coxiella burnetii, which causes Q fever. The new study, published Jan. 13 in the Journal of General Internal Medicine, sought to find out how often people likely develop ME/CFS after a bout of COVID-19.
“By my rough calculations it is possible that over 7 million Americans may have developed ME/CFS following COVID,” Beth Pollack, a research scientist at MIT who studies ME/CFS and long COVID, told Live Science in an email.
Pollack, who was not involved in the study, said this estimate is based on the new research, as well as U.S. Census Bureau statistics and the CDC Household Pulse Survey, which was designed to rapidly assess impacts of the coronavirus pandemic across the United States.
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ME/CFS (formerly called “chronic fatigue syndrome”) affects roughly 1 in 100 adults in the U.S. One of its main components is post-exertional malaise, in which people’s symptoms suddenly worsen after physical or mental exertion. People with the condition often experience unrefreshing sleep, brain fog and orthostatic intolerance, or sudden blood-pressure dips upon standing. Doctors are still trying to understand the biological causes of this understudied condition, but as of yet, no approved treatments exist.
Notably, ME/CFS has many overlapping symptoms with long COVID, an umbrella term that describes a range of health issues that emerge or worsen after a COVID-19 infection. Scientists are not yet sure if ME/CFS and long COVID are separate illnesses, said Dr. Anthony Komaroff, a professor of medicine at Harvard Medical School and senior physician at Brigham and Women’s Hospital who was not involved in the study.
Emerging evidence suggests they might be “two examples of a larger illness that humans and other animals can experience after an infection or a major non-infectious injury,” Komaroff told Live Science in an email.
Tracking ME/CFS after COVID
To investigate the relationship between COVID-19 and ME/CFS, the researchers studied 11,785 U.S. adults who had contracted SARS-CoV-2, the virus that causes COVID-19. Most of the participants were vaccinated at the time of the study, and most were enrolled as the omicron variant of the virus was circulating.
The team also studied 1,439 adults who had never caught COVID-19. The status of this group was confirmed through negative results on tests that looked for the virus itself and for antibodies against it. Notably, antibody levels wane over time, so these tests can’t completely rule out infections that took place a long time ago.
At three-month intervals, all of the study participants completed questionnaires designed to track possible symptoms of ME/CFS. The researchers then grouped the participants based on symptom severity, monitoring whether they had all the symptoms needed for a diagnosis, only some symptoms or no symptoms at all.
Participants with a formal ME/CFS diagnosis before the study were excluded from the analysis. Typically, being diagnosed with ME/CFS requires meeting specific diagnostic criteria, which include fatigue accompanied by physical impairment, post-exertional malaise, unrefreshing sleep, and either cognitive impairment or orthostatic intolerance.
In the study, only 0.6% of people without a history of COVID-19 developed ME/CFS, compared with 4.5% of adults who developed the condition at least six months after having COVID-19. This suggests that COVID-19 significantly increases the risk of developing ME/CFS.
Pollack noted that 79.5% of people who developed ME/CFS in the study were female, which aligns with previous research showing that both ME/CFS and long COVID disproportionately affect females. “It will be critical to further study why this is, and to examine the roles of sex hormones and sex differences in pathological immune responses to infection,” she said.
The study also found that 88.7% of participants with ME/CFS after COVID-19 were also diagnosed with long COVID.
“Long COVID and ME/CFS have not only very similar symptoms, but very similar underlying abnormalities of the brain, immune system, energy metabolism and cardiovascular system,” Komaroff said.”In my opinion, both Long COVID and ME/CFS are likely to be examples of post-acute infection syndromes,” he said.
To strengthen their conclusions, the researchers used a technique called propensity score matching. This means they compared participants in the COVID-19 group with uninfected participants with similar demographics and preexisting conditions, to help minimize baseline differences between the groups.
But the team noted that some participants may have had undiagnosed ME/CFS before having COVID-19, which could be a limitation of the work. The questionnaire-based nature of the study presented another limitation, because participants may have struggled to remember whether their symptoms started before or after they had COVID-19.
Despite these limitations, the findings do suggest that COVID-19 raises the risk of ME/CFS. And currently, neither ME/CFS nor long COVID have approved treatments.
“This study’s findings underscore the urgent need for treatments,” Pollack said. “ME/CFS can be caused by multiple triggers in addition to SARS-CoV-2, and it has been among the least funded illnesses for research, despite its severity.”
