Investigation of BOLD signal intensities in long COVID patients using 7T functional MRI

Long COVID is increasingly associated with disruption in brain homeostasis, manifesting as severe neurological dysfunction, brain fog and cognitive impairment. This present study investigated localised cognitive deficits in long COVID patients by examining brain blood oxygenation-level-dependent (BOLD) signal activity using ultra-high-field 7 T (7T) task-based functional magnetic resonance imaging (fMRI). Whole-brain BOLD signal differences were assessed across 19 long COVID patients, and 27 healthy controls (HC) including 12 COVID-recovered (Cov-RHC) and 15 COVID-19-naïve HC (nHC). 225 fMRI volumes were acquired during the Stroop colour-word task. Functional and anatomical images were processed using SPM12 to extract the BOLD signal intensity time course from whole-brain voxels for inferences between cohorts during task-fMRI. Significantly low BOLD activation in long COVID patients was observed compared to Cov-RHC in the anterior cingulate cortex (p = 0.002, cluster size=650, Z-value = 4.67), and the precuneus (p = <0.001, cluster size = 1893, Z-value = 4.67). Furthermore, BOLD intensities in precuneus showed a negative association with self-reported pain scores (p = 0.040) and the duration of illness (p = 0.03) in long COVID patients, suggesting significant correlation between BOLD signal and an increase in duration of illness and pain levels. No statistically significant BOLD differences were observed for inter-group comparisons between nHC vs. long COVID, and nHC vs. Cov-RHC. Response times to incongruent (p = 0.002) and congruent task stimuli (p = 0.001) significantly varied between nHC and long COVID cohorts, demonstrating overall faster information processing by nHC. Reduced BOLD signals to 'core' brain regions in long COVID imply reduced cognitive control by intrinsic networks that mediate information processing, cognitive and executive functions due to perturbations linked to cerebral blood flow, oxygenation status, and ongoing neuroinflammation.