Neural basis of fatigue in post-COVID syndrome and relationships with cognitive complaints and cognition

The main objective was to evaluate structural and functional connectivity correlates of fatigue in post-COVID syndrome, and to investigate the relationships with an objective measure of mental fatigue and with subjective cognitive complaints. One-hundred and twenty-nine patients were recruited after 14.79 +/- 7.17 months. Patients were evaluated with fatigue, neuropsychological, and subjective cognitive complaints assessments. Structural and functional magnetic resonance imaging were acquired, and functional connectivity, white matter diffusivity and grey matter volume were evaluated. Fatigue was present in 86 % of patients, and was highly correlated to subjective cognitive complaints. Fatigue was associated with structural and functional connectivity mostly in frontal areas but also temporal, and cerebellar areas, showing mental fatigue different pattern of functional connectivity correlates compared to physical fatigue. White matter diffusivity correlates were similar in fatigue and subjective cognitive complaints, located in the forceps minor, anterior corona radiata and anterior cingulum. Findings confirm that fatigue in post-COVID syndrome is related to cerebral connectivity patterns, evidencing its brain substrates. Moreover, results highlight the relationship between fatigue and subjective cognitive complaints. These findings point out the relevance of the multidisciplinary assessment of post-COVID syndrome patients with subjective cognitive complaints, in order to unravel the symptomatology beneath the patient's complaints.