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February 27, 2024
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‘Frightening’ connections between long COVID, fibromyalgia, fatigue warrant more research

Fact checked byShenaz Bagha
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SCOTTSDALE, Ariz. — Long COVID, fibromyalgia and chronic fatigue syndrome demonstrate overlapping characteristics that warrant further investigation, according to a speaker at the Basic and Clinical Immunology for the Busy Clinician symposium.

Fatigue is the real kind of final frontier where we feel powerless in our clinics,” Leonard Calabrese, DO, RJ Fasenmyer chair of clinical immunology at the Cleveland Clinic, and chief medical editor of Healio Rheumatology, told attendees during the hybrid meeting. “It is not an insignificant symptom in our world, yet we run for the hills when patients talk about this.

Leonard Calabrese, DO, speaks at the Basic and Clinical Immunology for the Busy Clinician symposium.
“Fatigue is the real kind of final frontier where we feel powerless in our clinics,” Leonard Calabrese, DO, told attendees. “It is not an insignificant symptom in our world, yet we run for the hills when patients talk about this.”

“The question should be, what is the relationship between a number of these diseases?” he added.

According to Calabrese, a study from the Post-Acute COVID-19 Syndrome Clinic at Stanford University produced one “pretty frightening” data point, when researchers led by Hector F. Bonilla, MD, found that 43% of 140 patients referred there met Institute of Medicine criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). He cautioned that the sample was “very highly biased” and not population-based, but added the result suggests COVID-19 has the capacity to “make people display the features that meet fairly widely accepted criteria for ME/CFS.”

Calabrese also pointed to data suggesting connections between long COVID with fibromyalgia. Specifically, researchers have found that fibromyalgia can be a sequela to viral, bacterial or parasitic infections.

Also, analysis of National Databank for Rheumatic Diseases data found 41% of self-reported long COVID patients having a history of fibromyalgia vs. 13% of those who fully recovered from their infection, suggesting fibromyalgia “either can be indistinguishable or can be a big confounder,” Calabrese said. However, he granted there is “a lot” to go against fibromyalgia “being equivalent to long COVID,” and added that the whole question is ripe for further study.

“There are over 10,000 papers peer-reviewed and written about long COVID, and you can count the number that deal with fibromyalgia on fingers and toes,” Calabrese said. “Somehow it is not an acceptable paradigm in that community at the present time. It’s distressing to me.”

He added that it is important to know if long COVID and fibromyalgia are similar pathophysiologically because, if they are, then non-pharmacological interventions shown to be effective in fibromyalgia, such as graded exercise, cognitive behavioral therapy and mind-body techniques, may also improve long COVID outcomes.

Calabrese proposed a long COVID “research agenda” of the following questions:

  • What percent of patients meeting some long COVID definition meet fibromyalgia diagnostic criteria?
  • Do these patients differ from patients meeting the Institute of Medicine criteria for ME/CFS alone?
  • What is the prevalence of post-exertional malaise in primary fibromyalgia and immune-mediated inflammatory disease-associated fibromyalgia?

“These instruments are readily available, and we’re in the process of starting this project,” Calabrese said, referring to the first question.

He later added: “We are involved in several clinical trials of therapy, including an FcRn inhibitor, in dysautonomia from COVID-19.”