Examining Well-Being and Cognitive Function in People With Long COVID and ME/CFS, and Age-Matched Healthy Controls: A Case-Case-Control Study. — CFSMEATLAS
Examining Well-Being and Cognitive Function in People With Long COVID and ME/CFS, and Age-Matched Healthy Controls: A Case-Case-Control Study.
Sanal-Hayes, Nilihan E M, Mclaughlin, Marie, Hayes, Lawrence D et al. · The American journal of medicine · 2025 · DOI
Quick Summary
This study compared how people with long COVID and ME/CFS experience their daily well-being and thinking abilities, compared to healthy people of similar ages. Researchers found that both long COVID and ME/CFS patients reported similar struggles with fatigue, pain, sleep problems, anxiety, and difficulty with everyday activities—but their actual test performance on thinking tasks was comparable to healthy controls. The findings suggest that both conditions affect quality of life in very similar ways.
Why It Matters
This is the first direct comparison of well-being and cognitive function between long COVID and ME/CFS, demonstrating that despite different illness durations, both conditions produce similar patient-reported impacts on quality of life. Understanding these parallels could inform treatment strategies and validate long COVID patients' experiences while highlighting the urgent need for interventions addressing well-being in both populations.
Observed Findings
People with both long COVID and ME/CFS reported significantly worse fatigue severity, pain, post-exertional malaise, and sleep quality compared to healthy controls.
Both patient groups reported greater difficulty with mobility, self-care, and usual activities, as well as higher rates of anxiety and depression symptoms.
Objective cognitive test performance (SDMT, Stroop, Trails A/B) showed no significant differences between long COVID, ME/CFS, and control groups.
Neuro-symptom burden was substantially elevated in both patient groups relative to controls.
Self-efficacy was significantly reduced in both long COVID and ME/CFS patients.
Inferred Conclusions
Long COVID and ME/CFS produce comparable impairment in well-being and quality of life measures, suggesting shared disease mechanisms or symptom overlap despite different illness trajectories.
Objective cognitive dysfunction, as measured by standard neuropsychological tests, does not clearly distinguish either patient group from healthy controls, though subjective cognitive complaints are prominent.
Well-being-targeted interventions rather than condition-specific treatments may be appropriate for both long COVID and ME/CFS populations.
Remaining Questions
Will long COVID patients' well-being and cognitive profiles remain similar to ME/CFS patients as illness duration extends beyond 16 months, or will patterns diverge?
What This Study Does Not Prove
This study does not prove that long COVID and ME/CFS are identical conditions or have the same underlying biological mechanisms—only that they produce similar symptomatic profiles at these timepoints. It does not establish whether objective cognitive impairment exists that standard tests cannot detect, nor does it determine whether longer illness duration in ME/CFS leads to psychological adaptation or genuine stability. The cross-sectional design cannot establish causality or predict how long COVID patients will fare at longer illness durations.
Do objective cognitive tests lack sensitivity to detect the cognitive impairment both groups self-report, and would alternative testing methods (fMRI, eye-tracking, processing speed tasks) reveal objective deficits?
What are the underlying biological mechanisms driving the similar well-being impairment in both conditions, and are they related to post-exertional malaise or other shared pathophysiology?
Which specific interventions targeting well-being (rehabilitation, psychological support, pharmacological) would be most effective for either or both conditions?