Does COVID Infection Carry a Small Risk of Chronic Fatigue Syndrome?

Researchers in Germany say they cannot rule out a small risk for key symptoms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children who had a COVID-19 infection.

In a cross-sectional study involving more than 600 children, a crude analysis found that clustered ME/CFS symptoms were more frequently reported in those with SARS-CoV-2 seropositivity compared to those who were seronegative (40.0% vs 29.6%; risk ratio [RR] 1.35 95% CI 1.03-1.78), according to Anna-Lisa Sorg, MSc, of Ludwig-Maximilians-University Munich, and colleagues.

However, after adjusting for sex, age, and pre-existing disease, the association was smaller and no longer statistically significant (adjusted RR 1.18, 95% CI 0.90-1.53), as shown in the team’s study in JAMA Network Open.

A risk for substantial fatigue in the seropositive group was seen in both crude (11% vs 4.5%; RR 2.45, 95% CI 1.24-4.84) and adjusted (RR 2.08, 95% CI 1.05-4.13) analyses.

But the effect sizes for all outcomes were “reduced markedly” when the researchers only examined patients who were unaware of their SARS-CoV-2 status:

• Clustered ME/CFS symptoms: RR 1.08 (95% CI 0.80-1.46)
• Substantial fatigue: RR 1.43 (95% CI 0.63-3.23)

“These findings suggest that the risk of ME/CFS in children and adolescents owing to SARS-CoV-2 infection may be very small,” wrote Sorg and coauthors, adding that “recall bias may contribute to risk estimates of long COVID-19 symptoms in children.”

Data for the study — a substudy of the cross-sectional SARS-CoV-2 seroprevalence surveys in Germany (SARS-CoV-2 KIDS) — were gathered at nine hospitals and included children treated in the inpatient or outpatient setting for any reason. To assess ME/CFS symptoms, parents of the children received the the DePaul Symptom Questionnaire (DSQ), a screening tool for ME/CFS in children and adolescents ages 5 to 17 years old.

“This is a study of a small number of fatigued kids,” said Leonard Jason, PhD, creator of the DSQ and the director of the Center for Community Research at DePaul University in Chicago, who cautioned that the German researchers “may have overreached” in their conclusion.

“There’s a large difference between youth who are feeling unwell, feeling fatigue, and having something more severe called ME/CFS,” Jason told MedPage Today. “Those distinctions are critical to understanding ME/CFS.”

Jason noted that the researchers never asked parents, “‘Has your kid ever been diagnosed with CFS?’ — This is the basic question to ask.”

For their study, Sorg’s group enrolled 634 children from May to October 2021. Participants had a median age of 11.5 years and 46% were boys. Overall, 100 were seropositive and 534 were seronegative for SARS-CoV-2.

Overall, 31% reported clustered ME/CFS symptoms (n=198). This was more common among girls (37.3% vs 24.1% in boys), in kids 14 and older (41.1% vs 26.8%), and in those with a pre-existing disease (36.7% vs 26.4%).

The DSQ asks about typical ME/CFS features including “frequent and persistent fatigue or extreme tiredness, pain, sleeping problems, cognitive difficulties, flu-like symptoms, or disruptions in school activities,” the researchers explained.

Clustered ME/CFS symptoms were defined as fatigue and/or school or cognitive difficulties and at least four additional symptoms in the past 3 months, and at least half the time. Fatigue had to be at least moderate in severity.