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

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.

Similar patterns of 18F-FDG brain PET hypometabolism in paediatric and adult patients with long COVID: a paediatric case series (preprint)

Purpose: Several weeks after COVID-19 infection, some children report the persistence or recurrence of functional complaints. This clinical presentation has been referred as “long COVID” in the adult population, and an 18 F-FDG brain PET hypometabolic pattern has recently been suggested as a biomarker. Herein, we present a retrospective analysis of 7 paediatric patients with suspected long COVID who were explored by 18 F-FDG brain PET exam. Metabolic brain findings were confronted to those obtained in adult patients with long COVID, in comparison to their respective age-matched control groups. Methods: . Review of clinical examination, and whole-brain voxel-based analysis of 18 F-FDG PET metabolism of the 7 children in comparison to 20 paediatric controls, 35 adult patients with long COVID and 44 healthy adult subjects. Results: . Paediatric patients demonstrated a similair brain hypometabolic pattern as that found in adult long COVID patients, involving bilateral medial temporal lobes, brainstem and cerebellum (p-voxel < 0.001, p-cluster < 0.05 FWE-corrected), and also the right olfactory gyrus after small volume correction (p-voxel = 0.010 FWE-corrected), with partial recovery in two children at follow-up. Conclusion: These results provide arguments in favour of possible long COVID in children, with a similar functional brain involvement to those found in adults .

18F-FDG brain PET metabolism in post-SARS-CoV-2 infection: substrate for persistent/delayed disorders? (preprint)

Purpose: Several brain complications of SARS-CoV-2 infection have been reported. It has been moreover speculated that this neurotropism could potentially cause a delayed outbreak of neuropsychiatric and neurodegenerative diseases of neuroinflammatory origin. A propagation mechanism has been proposed across the cribriform plate of the ethmoid bone, from the nose to the olfactory epithelium, and possibly afterwards to other limbic structures, and deeper parts of the brain including the brainstem. Methods: : Review of clinical examination, and whole-brain voxel-based analysis of 18 F-FDG PET metabolism in comparison to healthy subjects (p-voxel<0.001, p-cluster<0.05), of two patients with confirmed diagnosis of SARS-CoV-2 pneumonia explored at the post-viral stage of the disease. Results: : Hypometabolism of the olfactory/rectus gyrus was found on the two patients, especially one with 4 weeks prolonged anosmia. Additional hypometabolisms were found within bilateral amygdala, hippocampus, cingulate cortex, thalamus, pons and medulla brainstem in the other patient who complained of delayed onset of an atypical painful syndrome. Conclusion: These preliminary findings reinforce the hypotheses of SARS-CoV-2 neurotropism through the olfactory bulb, and the possible extension of this impairment to other limbic structures and to the brainstem. 18 F-FDG PET hypometabolism could constitute a cerebral quantitative biomarker of this involvement. Post-viral cohort studies are required to specify the exact relationship between limbic/brainstem hypometabolisms and the possible persistent disorders, especially involving cognitive or emotion disturbances, residual respiratory symptoms or painful complaints.