Serena Fineschi ^1,2* Markus Fahlström ³ David Fällmar ^3,4 Sven Haller ^3,5,6 Johan Wikström ^3,4

• ¹ Department of Public Health and Caring Sciences, Faculty of Medicine, Uppsala University, Uppsala, Sweden
• ² Östhammar Health Care Centre, Östhammar, Sweden
• ³ Department of Surgical Sciences, Faculty of Medicine, Uppsala University, Uppsala, Uppsala, Sweden
• ⁴ Department of Radiology, Uppsala University Hospital, Uppsala, Uppsala, Sweden
• ⁵ Division of Radiodiagnostic and Interventional Radiology, Faculty of Medicine, University of Geneva, Geneve, Switzerland
• ⁶ Medical Imaging Center Cornavin SA Geneva, Geneve, Switzerland

Background: Impaired cognitive ability is among the most frequently reported neuropsychiatric symptoms in Post-COVID. It is unclear whether this is related to structural or functional brain changes.Purpose: In this study we present a multimodal magnetic resonance imaging study of 36 post-COVID patients and 36 individually matched controls who all had mild SARS CoV-2 infection from Mars 2020 to February 2022. The aim was to investigate structural and functional brain alterations, and their correlation with post-COVID symptoms, and neurocognitive functions.Material and Methods: Study protocol comprised assessment of physical fatigue (FSS), mental fatigue (MFS), depression (MADRS), anxiety (HAD), post-COVID symptoms severity score and neurocognitive status (RBANS). Magnetic resonance imaging protocol included morphological sequences, ASL and DSC perfusion, DTI, and resting state fMRI sequences. From these, assessments of macrostructural abnormalities, perfusion, grey matter density, white matter integrity, and brain connectivity were performed.Results: Post-COVID patients had higher levels of physical fatigue, mental fatigue, depression and anxiety than controls, and showed cognitive impairment in all RBANS domains except in Visuospatial/Construction. The subjective mental fatigue correlated with objective impaired cognitive ability at the RBANS test, particularly in the Attention domain.There were no differences between patients and controls regarding macrostructural abnormalities, regional volumes, regional perfusion metrics, grey matter density or DTI parameters.We observed a significant positive correlation between RBANS total scale index score and grey matter volume in right superior/middle temporal gyrus (p<0.05 ), and a significant negative correlation between white matter integrity and post-COVID symptoms (p<0.05) in the same area. Connectivity differences were observed between patients and controls in a few regions, including the right middle frontal gyrus, an important area of convergence of the dorsal and ventral attention networks. We also noted a positive correlation between post-COVID symptoms and increased connectivity in right temporoparietal junction, which is part of the ventral attention system.In non-hospitalized subjects with post-COVID, we did not find any structural brain changes, or changes in perfusion compared to controls. We did find differences in connectivity in an important area for attention processes, which may be involved in post-COVID brain fog.