SARS-CoV-2 disrupts the choroid plexus (ChP) epithelium by binding to the ACE-2 receptor, causing blood cerebrospinal fluid barrier leakage and permitting interleukin (IL)-6 and pathogens into the brain, subsequently leading to demyelination, white matter (WM) damage in long COVID, and clinical worsening. The role of the ChP in long COVID and its relationships to WM integrity, IL-6, clinical symptoms, and ACEIs/ARBs medications remains unclear. Fifty-two long COVID individuals, 21 COVID-19 survivors, and 26 healthy controls (HCs) completed Montgomery-Asberg Depression Rating Scale (MADRS), Montreal Cognitive Assessment (MoCA) and interleukin (IL) -6 assessments. Manually segmented ChP volume and global free water corrected WM integrity was compared among groups, and consideration of ACE inhibition on the ChP was examined. Partial correlations explored relationships among ChP volume, IL-6, fractional anisotropy tissue (FAt), and symptoms. ChP changes were also assessed at baseline and after one year. Long COVID individuals showed higher MADRS (p < 0.001), lower MOCA score (p < 0.001), and smaller ChP volume (p = 0.02) among groups. Larger ChP volume was significantly correlated to higher IL-6 levels (r = 0.478, p = 0.005) in long COVID. No ChP volume differences were found over time in the long COVID group or HCs that transitioned to COVID-19 survivors. COVID-19 survivors had larger ChP volume at follow-up compared to baseline (p = 0.04). The smaller ChP in long COVID seems to involve persistent but low-grade blood-CSF barrier dysfunction and epithelial stress. IL-6 levels may affect ChP permeability and suggest ongoing neuroinflammation in the long COVID group.
