Biomarkers

Background: The COVID-19 pandemic is a public health crisis, and its lasting consequences are not yet fully understood. Epidemiological data suggest that low- and middle-income countries, such as Brazil, will bear a considerable burden of COVID-19-related comorbidities. Individuals who have survived COVID-19 often report persistent symptoms, including neurological manifestations such as brain fog. However, the underlying brain biological changes behind the neurological symptoms remain undefined. Here, our goal was to assess the influence of long-COVID on brain metabolism in adults from a Brazilian cohort.

Method: Brazilian individuals (n=49) were recruited, examined through clinical and neuropsychological assessments, and divided into Control and Long-COVID groups. Then, they underwent a brain [¹⁸F]FDG-PET scan. Images were normalized by the global mean. Differences between groups were assessed through a [¹⁸F]FDG-PET voxel-wise linear regression accounting for age, sex and years of education (Table 1). The analysis was corrected for multiple comparisons using the cluster-wise random field theory method (significant t < -3.28 and t > 3.28).

Result: Long-COVID group exhibited recurring symptoms such as fatigue, memory complaints and lack of concentration (Table 1). They also exhibited hypometabolic clusters in the left superior parietal lobe (t_max=-4.03; p < 0.001) and right insular cortex (t_max=-3.31; p < 0.001) (Figure 1). Hypermetabolic clusters were found in the left whole cerebellum (t_max=4.92; p < 0.0001), right dorsolateral prefrontal cortex (t_max=3.83; p < 0.001), and right postcentral gyrus (t_max=4.24; p < 0.001) (Figure 2).

Conclusion: Our preliminary results demonstrate region-dependent dual response on brain metabolism due to Long-Covid. More specifically, glucose hypometabolism was found in regions associated with cognitive domains and affective modulation. By contrast, glucose hypermetabolism was observed in brain areas associated with motor coordination and sensory processing. Metabolic changes in these regions should be further evaluated to advance in the understanding of the pathophysiological mechanisms associated with persistent neurological manifestations seen in individuals presenting with Long COVID.