Reorganization of brain connectivity in post-COVID condition: a 18F-FDG PET study

Abstract

Background: A hypometabolic brain pattern has been reported in patients with post-COVID condition (PCC). The aim of this study was to investigate reorganization in metabolic connectivity in patients with PCC.

Results: One hundred eighty-eight patients who underwent brain ¹⁸F-FDG PET for PCC were retrospectively included from two university hospital centres. These patients were age- and sex-matched to 120 healthy controls who underwent brain ¹⁸F-FDG PET before the COVID-19 outbreak. A voxel-based group comparison between patients and controls was performed (p-voxel at 0.005 uncorrected, p-cluster at 0.05 FWE corrected). Interregional correlation analyses of the identified clusters as well as sparse inverse covariance estimations at whole-brain scaling were also conducted. Both analyses were performed at the group level for all patients and then secondarily according to the postinfection delay; 88 and 100 patients, respectively, had a delay of less than or greater than 9 months (± 9 M). Three hypometabolic clusters, namely, the right frontotemporal, right and left cerebellar, were identified from the voxel-based group comparisons of PCC patients. Within this hypometabolic PCC pattern, a modification in metabolic connectivity was observed in patients compared with controls, which was more marked in the + 9 M group than in the - 9 M group. On the other hand, the graph analysis revealed a decrease in connectivity efficiency metrics in the PCC.

Conclusions: Metabolic connectivity is modified in patients with PCC within the hypometabolic post-COVID-19 network, with lasting reorganization evolving over time, suggesting functional adaptation.

Fig. 1

Anatomical localization of hypometabolic clusters in post-COVID patients compared with controls (p-voxel < 0.005, uncorrected, p-cluster < 0.05 FWE corrected), projected onto 3D volume-rendered images for the whole population on the left, the less than 9 months from the infection group in the middle and the more than 9 months from the infection group on the right

Fig. 2

Anatomical localization of increased metabolic connectivity according to seed correlations in post-COVID patients compared with controls (p-voxel < 0.005, uncorrected, p-cluster corrected for the volume), projected onto 3D volume-rendered images for the right frontotemporal cluster (upper panel), the right cerebellar cluster (middle panel), the left cerebellar cluster (lower panel) and, for the whole population on the left, the less than 9 months from the infection group in the middle and the more than 9 months from the infection group on the right

Fig. 3

Sparse inverse correlation estimation of metabolic connectivity from post-COVID patients compared with controls for the whole population (upper panel), those less than 9 months from the infection group (middle panel) and those more than 9 months from the infection group (lower panel)