The COVID-19 pandemic has had a significant impact on the health of millions of people worldwide, and many manifest new or persistent symptoms long after the initial onset of the infection. One of the leading symptoms of long-COVID is cognitive impairment, which includes memory loss, lack of concentration, and brain fog. Understanding the nature and underlying mechanisms of cognitive impairment in long-COVID is important for developing preventive and therapeutic interventions.

Our present study investigated functional connectivity (FC) changes in patients with long-COVID and their associations with cognitive impairment. Resting-state functional MRI data from 60 long-COVID patients and 52 age- and sex-matched healthy controls were analyzed using seed-based functional connectivity analysis.

We found increased FC between the right caudate nucleus and both the left and right precentral gyri in long-COVID patients compared with healthy controls. In addition, elevated FC was observed between the right anterior globus pallidus and posterior cingulate cortex as well as the right temporal pole in long-COVID patients. Importantly, the magnitude of FC between the caudate and the left precentral gyrus showed a significant negative correlation with Montreal Cognitive Assessment (MoCA) scores and a negative correlation with Trail Making Test B performance in the patient group.

Patients with long-COVID present enhanced FC between the caudate and the left precentral gyrus. Furthermore, those FC alterations are related to the severity of cognitive impairment, particularly in the domain of executive functions.