ABSTRACT
Background: Little is still known about the mid/long-term effects of coronavirus disease 2019 (COVID-19) on the brain, especially in subjects who have never been hospitalized due to the infection. In this neuroimaging exploratory study, we analyzed the medium-term effect of COVID-19 on the brain of people who recovered from COVID-19, experienced anosmia during the acute phase of the disease, and have never been hospitalized due to SARS-Co-V-2 infection. Methods: Forty-three individuals who had (COV+, n = 22) or had not (COV-, n = 21) been infected with SARS-Co-V-2 were included in the study; the two groups were age- and sex-matched and were investigated using 3T magnetic resonance imaging (MRI). Gray matter (GM) volume, white matter (WM) hyperintensity volume, WM microstrutural integrity (i.e. fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD], radial diffusivity [RD]) and cerebral blood flow (CBF) differences between the two groups were tested with either analysis of covariance or voxel-wise analyses. Results were family wise error (FWE) corrected. Results: No significant differences between COV+ and COV- groups were observed in terms of GM volume, WM hyperintensity volume, and CBF. Conversely, local WM microstructural alterations were detected in COV+ when compared with COV- with tract-based spatial statistics. Specifically, COV+ showed lower FA (pFWE-peak = 0.035) and higher RD (pFWE-peak = 0.038) than COV- in several WM regions. Conclusion: COVID-19 may produce mid/long-term microstructural effect on the brain, even in case of mild-to-moderate disease not requiring hospitalization. Further investigation and additional follow-ups are warranted to assess if the alterations reported in this study totally recover over time. As brain alterations could increase the risk of cognitive decline, greater knowledge of their trajectories is crucial to aid neurorehabilitation treatments.