Abstract

Motivation: Long-COVID is a disabling health problem caused by SARS-COV-2 syndrome, whose underlying biological mechanisms are still debated. Goal(s): This study aimed at finding the set of quantitative MRI (qMRI) metrics that best correlate with fatigue, smell (i.e. anosmia),and cognitive dysfunction, common in this condition. Approach: People with COVID19 history with and without long-COVID were assessed through a multimodal one-hour-long qMRI protocol and underwent clinical evaluation. Results: Correlation analyses between qMRI metrics and clinical scores showed that neurite density index changes explain both fatigue and smell function (also affected by changes in brain stem volume),while mean diffusivity and magnetic susceptibility changes explain cognitive function. Impact: This work sheds light on the underlying biological mechanisms of long-COVID (anosmia, fatigue, and cognitive impairment). Metrics sensitive to microstructure, inflammation and possible iron accumulation best explain persistent symptoms, emphasizing the role of multimodal qMRI in the clinic.