The authors studied blood-brain barrier (BBB) dysfunction in patients during acute SARS-Cov2 infection (76 inpatients and 25 pre-pandemic controls). Several pro-inflammatory cytokines, growth factors and markers of thrombosis and endothelial cell activation were increased in COVID-19 patients. These increased even further in patients with more severe disease and in patients with brain fog, with levels of S100β, a marker of BBB dysfunction, basic fibroblast growth factor (bFGF), IL-13, IL-6 and GM-CSF being particularly high. Subsequently, they enrolled 10 patients who recovered from COVID-19, 11 with long COVID-19 (LC) with no brain fog and 11 with LC and brain fog (LC-bf). Dynamic contrast enhancement MRI was used to assess BBB permeability and repeated blood sampling was performed. Significantly increased BBB permeability, particularly in the fronto and temporal lobes, was found in the LC-bf cohort compared to LC and recovered patients. Regional BBB permeability in the temporal lobes was correlated with anosmia but not with cognitive impairment. IL-1RA, IL-1β, bFGF and IL-13 were elevated in all COVID-19 groups in the chronic phase compared to controls. Glial fibrillary acidic protein (GFAP) was increased in LC-bf compared to recovered individuals while transforming growth factor-β (TGFβ) was selectively increased in the LC-bf group compared to LC.
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Observational study: prospective longitudinal cohort