Brain connectivity and its relation to cognitive function in patients with post-COVID 19 condition after mild infection

Neurological symptoms are common in post-COVID-19 condition (PCC) and have been linked to underlying brain alterations. However, in individuals with PCC following a mild infection without hospitalization, such alterations are rarely detected using conventional neuroimaging techniques. This study aims to investigate brain connectivity in patients with PCC with cognitive symptoms after mild COVID-19 infection, using resting-state functional magnetic resonance imaging (rs-fMRI). Additional aims were to explore associations between brain connectivity, neuropsychological performance, and self-reported fatigue and emotional status. Patients with PCC (n = 22) and lasting cognitive symptoms and fatigue were consecutively recruited from a regional rehabilitation unit and compared with a convenience sample of non-symptomatic controls (n = 19). The assessments were conducted on average 32 months post-infection and included 3 Tesla rs-fMRI, neuropsychological testing, and self-report measures of fatigue (MFI-20), anxiety, and depression (HADS). Patients with PCC had elevated functional connectivity in brain regions associated with the default mode network (DMN) compared to controls. No significant correlations were found between functional connectivity, neuropsychological test performance, fatigue, anxiety, or depression. Our findings suggest persistent alterations in DMN connectivity in PCC with cognitive symptoms and fatigue, underscoring the need for continued larger studies on brain functioning in this patient group. Clinical trial registration: No. NCT06042530.