Persistent neurocognitive deficits in long COVID: Evidence of structural changes and network abnormalities following mild infection

This study aimed to investigate the neurocognitive deficits, structural brain alterations, and network abnormalities in individuals who had a mild SARS-CoV-2 infection, with and without brain fog, as a symptom of long COVID. A cross-sectional study was conducted involving 75 participants, categorized into three groups: 24 healthy controls (HCs), 26 COVID-19 survivors without brain fog (woFOG), and 25 with brain fog (wFOG). Neuropsychological assessments included the Free and Cued Selective Reminding Test (FCSRT) and Addenbrooke’s Cognitive Examination–Revised (ACE-R). Structural and functional brain alterations were examined using voxel-based morphometry (VBM) and resting-state functional MRI (rs-fMRI). The wFOG group exhibited significant cognitive impairments, particularly in delayed free recall, attention, memory, and visuospatial skills, compared to both the woFOG and HC groups. Structural MRI analyses revealed reduced gray matter concentrations (GMC) in the left inferior temporal gyrus, left fusiform gyrus, and right orbital gyri in both COVID-19 groups relative to HCs. Additionally, the wFOG group exhibited further GMC reductions in the bilateral caudate nuclei, right putamen/pallidum, and amygdala compared to the woFOG group. rs-fMRI analyses demonstrated altered connectivity patterns in COVID-19 survivors, characterized by increased connectivity in the default mode network and visual networks, alongside decreased connectivity in the dorsal attention network. These findings indicate that even mild COVID-19 can result in persistent neurocognitive deficits, structural brain alterations, and functional network abnormalities, both in individuals with and without brain fog. The observed changes highlight the importance of long-term monitoring and targeted interventions to address potential cognitive and neurological consequences of long COVID.