Functional and microstructural brain abnormalities, fatigue, and cognitive dysfunction after mild COVID-19

Silva, L. S.; Joao, R. B.; Nogueira, M. H.; Aventurato, I. K.; de Campos, B. M.; de Brito, M. R.; Alvim, M. K. M.; Ludwig, G. V. N.; Rocha, C.; Souza, T. K. A. S.; da Costa, B. A.; Mendes, M. J.; Waku, T.; Boldrini, V. d. O.; Brunetti, N. S.; Baptista, S. N.; Schmitt, G. d. S.; Sousa, J. G. D. d.; Cardoso, T. A. M. d. O.; Vieira, A. S.; Santos, L. M. B.; Farias, A.; Cendes, F.; Yasuda, C. L.

Although post-acute cognitive dysfunction and neuroimaging abnormalities have been reported after hospital discharge in patients recovered from COVID-19, little is known about persistent, long-term alterations in people without hospitalization. We conducted a cross-sectional study of 87 non-hospitalized recovered individuals 54 days after the laboratory confirmation of COVID-19. We performed structured interviews, neurological examination, 3T-MRI scans with diffusion tensor images (DTI) and functional resting-state images (fMRI). Also, we investigated fatigue, anxiety, depression, somnolence, language, memory, and cognitive flexibility, using validated instruments. Individuals self-reported a high frequency of headache (40%) and memory difficulties (33%). The quantitative analyses confirmed symptoms of fatigue (68%), excessive somnolence (35%), anxiety (29%), impaired cognitive flexibility (40%) and language impairment (33%). There were widespread cerebral white matter alterations (mainly characterized by increased fractional anisotropy), which correlated with abnormal attention and cognitive flexibility. The resting-state fMRI networks analysis showed severely disrupted brain hyperconnectivity and loss of resting-state networks specificity.