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AIM: Up to 10% of SARS-CoV-2 infected individuals suffer from post-COVID-19 condition, marked by fatigue and cognitive dysfunction as major symptoms. Longitudinal studies on neuropsychological and clinical trajectories and related brain changes are scarce. Here, we aimed to examine their evolution up to 2 years post-infection. METHODS: In a multi-center, longitudinal study of 79 post-COVID patients (mean age 46, 48 female) with persistent symptoms and 21 age- and sex-matched never-infected, healthy controls (mean age 42, eight female), we analyzed neuropsychological performance, self-reported outcomes and associated neuroimaging alterations of resting-state functional and structural magnetic resonance imaging data 23 months post-infection. RESULTS: In post-COVID patients 23 months after SARS-CoV-2 infection we observed (1) that fatigue severity had reduced but still remained present in most patients, (2) widespread brain changes involving the brainstem, the pre- and postcentral gyrus and the limbic olfactory network, (3) a weakening of self-reported fatigue and its cerebral associations. Notably, findings of brain aberrations were more pronounced in hospitalized patients. CONCLUSION: Our findings indicate that complex brain adaptations take place up to 2 years following SARS-CoV-2 infection. Some regions manifest enduring abnormalities while others undergo restitution. The attenuation of radio-clinical associations suggests a compensatory function for these regions, pointing to non-brain intrinsic factors to sustain persistent fatigue.
Dadsena et al. (Tue,) studied this question.