From inflammation to degeneration – Enlarged perivascular spaces and glymphatic clearance in neuropsychiatric long-COVID syndrome

Abstract

Neuropsychiatric symptoms, such as executive dysfunction, fatigue and depression, are highly prevalent and severely incapacitating among Long- and Post-COVID patients (Schou et al., 2021), to the point where some are unable to resume their jobs and even their daily lives. While the prognosis of these patients remains elusive, cognition worsens over time in many of them (Lu et al., 2020). Perivascular inflammation in the brain, as a consequence of the blood-brain barrier damage caused by SARS-CoV-2 (Yang et al., 2020), is one of the mechanisms of ongoing systemic and intracerebral inflammation proposed to contribute to these long-lasting symptoms. We thus investigated two surrogate measurements of glymphatics, enlarged perivascular spaces in T1-w magnetic resonance imaging and three-dimensional propagation of cardiorespiratory pulsations in ultrafast magnetic resonance encephalography (Barghoorn et al., 2021), in 60 neuropsychiatric long-COVID patients, 30 healthy COVID-19 survivors and 30 never-infected healthy controls. We provide evidence of EPVS burden being associated with cognitive impairment and cardiorespiratory pulsations slightly varying among these groups. We hypothesize glymphatic clearance dysfunction might be a way for post-COVID to transition into a neurodegenerative disorder.