Long-COVID patients with severe fatigue report little relief by 20 months

Fatigued man sitting on bed

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Patients diagnosed as having long COVID and myalgic encephalitis/chronic fatigue syndrome (ME/CFS) reported that most symptoms remained severe up to 20 months after SARS-CoV-2 infection, while those with long COVID alone reported improvement, according to a recent observational study in eClinicalMedicine.

Researchers at Charite Universitatsmedizin Berlin evaluated symptom severity and biomarkers in 106 patients with long COVID (post-COVID syndrome [PCS]) who had moderate to severe fatigue and exertion intolerance. They assessed them at 9 to 16 and/or 17 to 20 months after infection from July 2020 to February 2022. The team based its findings on physician-supervised patient questionnaires and clinical, functional, and lab results.

The authors noted that some long-COVID patients with severe fatigue and exertion intolerance also meet the criteria for ME/CFS, a neuro-immunologic disease characterized by these symptoms and post-exertional aggravation of symptoms that can lead to physical disability. Patients with long COVID alone have similar symptoms but in general have milder post-exertion symptoms that resolve sooner.

Patients still fatigued at 16 months

Fifty-five patients met the Canadian Consensus Criteria (CCC) for ME/CFS and were classified as having PCS-ME/CFS, and the other 51 were classified as having PCS alone. Only 7 of the 55 patients (13%) in the former group saw improvement in their physical impairments over time.

At baseline, patients with long COVID alone had, on average, a lower Chalder Fatigue Score (CFQ) than patients with PCS-ME/CFS, with 33% of long-COVID and 55% of PCS-ME/CFS patients reporting severe fatigue (at least 28 CFQ points).

While CFQ scores remained high in the PCS-ME/CFS group over time, they declined significantly in patients with PCS alone. At 9 to 16 months, only 3% of long-COVID patients but 46% of those with PCS-ME/CFS still reported CFQ scores of 28 points or higher.

The duration, severity, and frequency of post-exertional malaise (PEM) were significantly higher in PCS-ME/CFS patients than in those with PCS alone at baseline and remained higher up to 9 to 16 months.

While neither group reported a reduction in PEM duration, PEM frequency and severity improved over time. PEM duration fell below 10 hours in seven (17%) of the PCS-ME/CFS group at 9 to 16 months, no longer fulfilling CCC. Five of the seven reported similar improvement in PEM severity and frequency.

In addition to ramping up our efforts to find effective therapies, this means we also need to quickly establish healthcare facilities where patients can receive multidisciplinary care based on current scientific findings and clinical experience.

Both PCS-alone and PCS-ME/CFS had a low median Bell disability score (40) at baseline, with only 4 of 55 PCS-ME/CFS and 1 of 51 PCS-alone patients reporting that they were too debilitated to leave their homes. A lower Bell score indicates greater disability.

But 53 of 55 PCS-ME/CFS and 43 of 51 PCS patients said that they couldn't work even part-time (Bell scale, fewer than 70 of 100). By 9 to 16 months, PCS-ME/CFS patients still had a Bell scale of 40, but PCS patients' Bell scales rose to 60, with only 12% of PCS-ME/CFS but 43% of PCS patients having a Bell score of 70 or higher.

Nineteen participants dropped out of the study; 63% of them were initially diagnosed as having PCS, and the remainder were diagnosed as having PCS-ME/CFS. Of the 70% of the dropouts who chose not to continue in the study because their symptoms had improved, two diagnosed as having PCS-ME/CFS disenrolled because of severe symptoms, and the remainder cited non–disease-related reasons.

Hand grip strength may be prognostic factor

Hand grip strength (HGS), an objective indication, was diminished in PCS-ME/CFS patients and was tied to disease severity at baseline and to symptom burden at follow-up. A low HGS average and maximum force at baseline correlated with increased fatigue, PEM, functional disability, pain, sleep disturbances, and emotional problems at 3 to 8 months.

A high HGS fatigue ratio—indicating faster fatigability—at baseline correlated with more fatigue and functional disability at 3 to 8 months and low baseline HGS recovery ratios correlated with increased fatigue and disability at 9 to 16 months. There were fewer and weaker correlations of HGS parameters at baseline with symptom outcomes at follow-up in PCS patients.

"Grip strength was not only a parameter for how severe the disease was to start with, but also a predictor of how ME/CFS would progress," co-principal investigator Carmen Scheibenbogen, MD, said in a Charite Universitatsmedizin Berlin press release. "Before we can use grip strength as a prognostic factor, though, we need further studies to confirm how meaningful it is."

Scheibenbogen said that the number of Europeans with ME/CFS has doubled since the pandemic began. "Our study shows that most people with ME/CFS remain severely ill," she said. "In addition to ramping up our efforts to find effective therapies, this means we also need to quickly establish healthcare facilities where patients can receive multidisciplinary care based on current scientific findings and clinical experience."

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