Slight recovery of brain metabolic impairment in patients with persistent long COVID: a nine-month follow-up [18F]FDG-PET study

Abstract

Abstract Purpose A hypometabolic profile involving the limbic areas, brainstem and cerebellum has been identified in long COVID patients via cerebral [18F]fluorodeoxyglucose (FDG)-PET. This study was conducted to evaluate possible recovery of brain metabolism during the follow-up of patients with prolonged symptoms. Methods Fifty-six adults with long COVID who underwent two brain [18F]FDG-PET scans in our department in May 2020–October 2022 were retrospectively analysed and compared to 51 healthy subjects. On average, PET1 was performed 7 (range 3–17) months after acute COVID-19 infection, and PET2 was performed 16 (range 8–32) months after acute infection. PET was performed because of persistent symptoms, including the following conditions: asthenia, cognitive complaints, dyspnoea, and sleep disorders. Whole-brain voxel-based analysis compared PET1 and PET2 from long COVID patients to scans from healthy subjects (p-voxel < 0.001 uncorrected, p-cluster < 0.05 FWE-corrected) and PET1 to PET2 (with the same threshold and with a less constrained threshold of p-voxel < 0.005 uncorrected, p-cluster < 0.05 uncorrected). Results PET1 and PET2 scans revealed hypometabolism in the previously reported profile. The between-group analysis comparing PET1 and PET2 showed minor improvements in the pons and cerebellum (8.4 and 5.2%, respectively, only significant under the less constrained uncorrected p-threshold); for the pons, the improvement was correlated with the PET1-PET2 interval (r = 0.21, p < 0.05). Of the 14,068 hypometabolic voxels identified on PET1, 6,503 were also hypometabolic on PET2 (46%). Of the 7,732 hypometabolic voxels identified on PET2, 6,094 were also hypometabolic on PET1 (78%). Conclusion Subjects with persistent symptoms of long COVID exhibit durable changes in brain metabolism, with only slight improvement 9 months later.