Objective: Persisting neurological symptoms after COVID-19 affect up to 10% of patients and can manifest in fatigue and cognitive complaints. Based on recent evidence, we evaluated whether cerebral hemodynamic changes contribute to post-COVID syndrome (PCS). Methods: Using resting-state functional magnetic resonance imaging, we investigated brain perfusion and oxygen level estimates in 47 patients (44.4 +/- 11.6 years; F:M = 38:9) and 47 individually matched healthy control participants. Group differences were calculated using two-sample t-tests. Multivariable linear regression was used for associations of each regional perfusion and oxygen level measure with cognition and sleepiness measures. Exploratory hazard ratios were calculated for each brain metric with clinical measures.<br /> Results: Patients presented with high levels of fatigue (79%) and daytime sleepiness (45%). We found widespread decreased brain oxygen levels, most evident in the white matter (false discovery rate adjusted-p-value (p-(FDR)) = 0.038) and cortical grey matter (p-(FDR) = 0.015). Brain perfusion did not differ between patients and healthy participants. However, delayed patient caudate nucleus perfusion was associated with better executive function (p-(FDR) = 0.008). Delayed perfusion in the cortical grey matter and hippocampus were associated with a reduced risk of daytime sleepiness (hazard ratio (HR) = 0.07, p = 0.037 and HR = 0.06, p = 0.034). Decreased putamen oxygen levels were associated with a reduced risk of poor cognitive outcome (HR = 0.22, p = 0.019). Meanwhile, lower thalamic oxygen levels were associated with a higher risk of cognitive fatigue (HR = 6.29, p = 0.017). Interpretation: Our findings of lower regional brain blood oxygen levels suggest increased cerebral metabolism in PCS, which potentially holds a compensatory function. These hemodynamic changes were related to symptom severity, possibly representing metabolic adaptations.
