Neurologic symptoms as a hallmark of glymphatic alteration in recovered patients with COVID-19.

Background: The glymphatic system is a glial-based perivascular network that facilitates the clearance of metabolic waste from the brain. Dysfunction of the glymphatic system, along with neurological symptoms such as cognitive deficits and olfactory dysfunction, has been reported in patients with coronavirus disease (COVID-19). However, the link between these neurological symptoms and alterations in the glymphatic system remains unclear. In this study, we aimed to evaluate magnetic resonance imaging (MRI)-based measures of the glymphatic system in patients recovered from COVID-19 with and without neurological symptoms.

Methods: This study included 89 patients who recovered from respiratory infections, of whom 71 had confirmed COVID-19 (20 experienced anosmia and 41 had cognitive symptoms). Three MRI-based measures were quantified and compared: the dilated perivascular spaces (dPVS), free water (FW) fraction, and diffusion tensor image analysis along the perivascular spaces (DTI-ALPS). A partial correlation network was used to assess the relationships between COVID-19 infection, neurological symptoms, and glymphatic measures.

Results: COVID-19 patients with anosmia had increased FW in the left orbitofrontal area compared to those without anosmia (mean difference: 0.01, p = 0.48), while patients with cognitive symptoms showed decreased left-sided DTI-ALPS (mean difference: 0.06, p = 0.40). Neurological symptoms mediate the relationship between COVID-19 and glymphatic system measures.

Conclusions: Our findings imply that neurological symptoms accompanied by COVID-19 are linked to distinct alterations in the glymphatic system, suggesting a potential association between neuroinvasion and neuroinflammatory processes related to COVID-19.