Cognitive impairment and associated neurobehavioral dysfunction in post-COVID syndrome

There is a high prevalence of neuropsychiatric sequelae in post-COVID syndrome, most commonly chronic fatigue, the mechanisms of which remain poorly understood. As altered function of the reward system has been suggested as a causal factor, we aimed to distinguish whether reward processing or task-unspecific cognitive operations are impaired in post-COVID syndrome. Our cohort study included 24 patients diagnosed with post-COVID syndrome and 24 demographically matched healthy controls. Questionnaire assessment of neuropsychiatric symptoms and socio-demographic variables, the Monetary Incentive Delay Task during an fMRI scan, and pupillary measurements were performed. In addition to clinical neuropsychiatric symptoms, participants in the post-COVID group demonstrated significantly slower task performance compared to healthy controls, although the function of behavioral reward circuits appeared unimpaired. However, the influence of rewarding cues on post-COVID patients increased significantly over time during task performance, correlating with temporally delayed activation of the left frontal gyrus and increased activity in task-unspecific brain regions in post-COVID patients. Furthermore, slower reaction times on the task were associated with a lower pupil diameter and a higher pupillary unrest index. This study proposes that post-COVID syndrome is a process that may not affect reward processing, but leads to neural hypoarousal and temporally altered brain activity in frontal and task-unspecific brain regions.