Assessing Brain Neurophysiology in COVID-19 Patients With Prolonged Cognitive Fatigue: A Comparison With Persistent Post-concussion Symptoms.

Introduction: Brain fog and cognitive dysfunction are frequently reported in post-viral fatigue syndromes such as long COVID, yet these symptoms remain challenging to quantify objectively. Notably, many individuals with long COVID describe clinical features that overlap with those observed in patients with persistent post-concussion symptoms (PPCS), including cognitive fatigue, exertional intolerance, mood disturbances, visual and balance problems, headaches, and neck pain. Emerging evidence suggests that PPCS is associated with distinct electrophysiological abnormalities, including altered functional connectivity (measured by electroencephalography (EEG) coherence), spatial changes in EEG amplitude distribution (notably increased frontal alpha and left-right asymmetry), and reduced cognitive evoked potentials (e.g., the auditory P300 response). In this study, we investigated whether these electrophysiological markers of PPCS are also present in individuals experiencing post-viral fatigue following COVID-19, aiming to provide objective measures to better characterize and quantify cognitive impairment in this population.

Materials And Methods: Thirty-one patients (mean age 45 ± 9 years) reporting persistent neurocognitive symptoms following COVID-19 infection (10 ± 2 months post-infection) were evaluated at intake to a brain injury clinic while seeking assessment/treatment for prolonged cognitive complaints. Over this time period, 64 PPCS patients (69% female; age: 42 ± 11 years) were evaluated at the same clinic for concussion-related symptoms using identical protocols. These were compared to seventy age-matched controls (mean age 45 ± 5 years) without a history of COVID-19 or neurological conditions. Assessments comprised standard concussion assessments with symptom profiles that included cognitive fatigue and EEG with event-related potentials (ERP). We then compared the EEG and ERP metrics known to be sensitive to declines in mental performance (i.e., PPCS) for both the long COVID group and age-matched controls.

Results: The long COVID cohort demonstrated neurophysiological alterations paralleling those observed in PPCS, including significantly impaired processing speed and reduced physical reaction times compared to controls (p < 0.001), as well as cognitive electrophysiological deficits, such as attenuated P300 amplitudes, which reflect impaired attention allocation (p < 0.001). These biomarkers normalized concomitantly with symptom resolution at long-term follow-up (mean 20 ± 8 months post-baseline assessment).

Conclusions: Our data demonstrate that ERP deficits, characteristic of cognitive decline in conditions like concussion, PPCS, and aging, are replicable in long COVID patients. Notably, these electrophysiological abnormalities (reduced P300 amplitude and altered coherence) correlate with quantifiable cognitive fatigue and functional neurological impairments. Biomarker normalization tracked with symptom resolution at follow-up (20 ± 8 months), confirming their clinical relevance. These accessible metrics provide objective parameters to identify virally induced cognitive deficits, addressing a critical need for validated diagnostic tools in post-viral syndromes.