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The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis / chronic fatigue syndrome and other chronic post-viral illnesses.
Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports — one published in the Journal of the American Medical Association in July and another published in Morbidity and Mortality Weekly Report this month — chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.
Although some of the reported persistent symptoms appear specific to SARS-CoV-2 — such as cough, chest pain, and dyspnea — others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.
At the virtual meeting of the International Association for Chronic Fatigue Syndrome / Myalgic Encephalomyelitis (IACFS/ME) last Friday, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.
"It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19," IACFS/ME co-vice-president Lily Chu, MD, told Medscape Medical News.
A Hint From the SARS Outbreak
This isn't the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Moldofsky, of the Department of Psychiatry (Emeritus) at the University of Toronto, Canada, reviewed data from a previously published case-controlled study, which included 22 healthcare workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1 to 3 years following the illness. None had been able to return to work by 1 year.
"We're looking at similar symptoms now" among survivors of COVID-19, Moldofsky said. "[T]he key issue is that we have no idea of its prevalence…We need epidemiologic studies."
Distinguishing ME/CFS From Other Post-COVID-19 Symptoms
Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.
Clinically, Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, post-exertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or two after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn't typical of ME/CFS.
Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.
While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught "pacing" in which the person conserves his or her energy by balancing activity with rest. "That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional," Chu said.
If a patient appears to be exhibiting signs of ME/CFS, "don't wait until they hit the 6-month mark to start helping them manage their symptoms," she said. "Teaching pacing to COVID-19 patients who have a lot of fatigue isn't going to harm them. As they get better they're going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy."
Will COVID-19 Unleash a New Wave of ME/CFS Patients?
Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.
Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.
Another project, funded by the Open Medicine Foundation (OMF), will follow patients who are discharged from the intensive care unit following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.
"We're taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS," said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at OMF and a faculty member at Harvard Medical School. The results, he said, "might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies."
Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization's new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS.
She noted that they've also teamed up with "Long-COVID" communities including Body Politic. "Our goal is to form a coalition to study together or at least harmonize data…and understand what's going on through the power of bigger sample sizes," Whittaker said.
None of the speakers have disclosed relevant financial relationships.
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