Fig. 3: COVID-associated brain changes.

a, Voxel-based morphometry map indicating brain regions with reduced volume in patients with previous SARS-CoV-2 infection. b–e, Group-wise comparison of total brain volume (P = 0.008 brain fog (+) versus control) (b), CSF volume (P = 0.021 recovered versus control; P = 0.006 brain fog (+) versus control) (c), right WM volume (P < 0.0001 recovered versus control; P = 0.00061 brain fog (+) versus control) (d) and left WM volume (P = 0.00014 recovered versus control; P = 0.00098 brain fog (+) versus control) (e) in unaffected individuals, recovered individuals and individuals with long COVID and brain fog. Data were analyzed using an ANCOVA, adjusting for age, sex and total intracranial volume (TIV), with Bonferroni correction. f, Surface-based morphometry map indicating brain regions with reduced cortical thickness in patients with previous SARS-CoV-2 infection. g–j, Group-wise comparison of frontal pole thickness (P = 0.003 recovered versus control; P = 0.002 brain fog (−) versus control; P = 0.001 brain fog (+) versus control) (g), superior frontal gyrus thickness (P = 0.003 brain fog (−) versus control; P = 0.008 brain fog (+) versus control) (h), middle temporal gyrus (P = 0.027 brain fog (+) versus control) (i) and superior temporal gyrus (P = 0.00012 brain fog (+) versus control) (j) in the unaffected, recovered, long COVID and brain fog cohorts. Data were analyzed using an ANCOVA adjusting for age and sex with Bonferroni correction. Maps were generated with Computational Anatomy Toolbox (CAT12) running in the Statistical Parametric Mapping (SPM12) software on MATLAB 2021a. The violin plots show the median (solid line) and IQR (dashed lines). Cohorts were compared with an unpaired t-test, with a family-wise error of less than 0.05, adjusted for age, sex and TIV. Volumetric and thickness region of interest measurements were obtained from volBrain.