Brain 18F-FDG PET imaging in outpatients with post-COVID-19 conditions: findings and associations with clinical characteristics

Abstract

Background Brain 18 F-FDG PET imaging has the potential to provide an objective assessment of brain involvement in post-COVID-19 conditions but previous studies of heterogeneous patient series yield inconsistent results. The current study aimed to investigate brain 18 F-FDG PET findings in a homogeneous series of outpatients with post-COVID-19 conditions and to identify associations with clinical patient characteristics. Methods We retrospectively included 28 consecutive outpatients who presented with post-COVID-19 conditions between September 2020 and May 2022 and who satisfied the WHO definition, and had a brain 18 F-FDG PET for suspected brain involvement but had not been hospitalized for COVID-19. A voxel-based group comparison with 28 age- and sex-matched healthy controls was performed (p-voxel at 0.005 uncorrected, p-cluster at 0.05 FWE corrected) and identified clusters were correlated with clinical characteristics. Results Outpatients with post-COVID-19 conditions exhibited diffuse hypometabolism predominantly involving right frontal and temporal lobes including the orbito-frontal cortex and internal temporal areas. Metabolism in these clusters was inversely correlated with the number of symptoms during the initial infection ( r = − 0.44, p = 0.02) and with the duration of symptoms ( r = − 0.39, p = 0.04). Asthenia and cardiovascular, digestive, and neurological disorders during the acute phase and asthenia and language disorders during the chronic phase ( p ≤ 0.04) were associated with these hypometabolic clusters. Conclusion Outpatients with post-COVID-19 conditions exhibited extensive hypometabolic right fronto-temporal clusters. Patients with more numerous symptoms during the initial phase and with a longer duration of symptoms were at higher risk of persistent brain involvement. Supplementary Information The online version contains supplementary material available at 10.1007/s00259-022-06013-2.

Association between olfactory dysfunction and mood disturbances with objective and subjective cognitive deficits in long-COVID

“…However, initial symptoms of COVID-19 are very relevant for long-term cognitive alterations. In this sense, recent research has shown that the symptoms during the initial phase of the disease, including olfactory dysfunction, could be determinants to produce brain alterations ( Goehringer et al, 2022 ). Brain hypometabolism correlated with high inflammation and impaired cognition, assessed with MoCA, and was associated with a higher number of symptoms at the time of the initial infection ( Goehringer et al, 2022 ).…”

“…In this sense, recent research has shown that the symptoms during the initial phase of the disease, including olfactory dysfunction, could be determinants to produce brain alterations ( Goehringer et al, 2022 ). Brain hypometabolism correlated with high inflammation and impaired cognition, assessed with MoCA, and was associated with a higher number of symptoms at the time of the initial infection ( Goehringer et al, 2022 ). This hypometabolism affects frontal, insular and temporal cortices, all regions of the olfactory brain network ( Guedj et al, 2021 ; Goehringer et al, 2022 ).…”

“…Damage to the olfactory bulb was demonstrated in long-COVID patients associated with long-term olfactory dysfunction ( Frosolini et al, 2022 ). This damage might extend to proximal and connected regions, affecting the limbic system and, consequently, impairing emotional and memory networks ( Díez-Cirarda et al, 2022 ; Goehringer et al, 2022 ; Kay, 2022 ; Martini et al, 2022 ). In fact, volume reduction and degeneration of brain areas connected to the olfactory bulb, such as the hippocampus, parahippocampal cortex, and the amygdala, with an important role in memory and emotional processing, were observed in brain scans of subjects who suffered mild COVID-19 infection ( Douaud et al, 2022 ).…”

Cortical Grey matter volume depletion links to neurological sequelae in post COVID-19 “long haulers”

“…GM changes in long COVID have also been documented using 18 fluorodeoxyglucose Positron Emission Tomography (PET) with decreases in metabolic activity among 28 consecutive outpatients, identified mainly in the right frontal and temporal lobes, but including orbito-frontal cortex and internal temporal and frontoparietal lobes [ 42 ]. Other studies involve decreases in cingulate cortex [ 43 ], or bilateral rectus/orbital gyrus including the olfactory gyrus, pre and post central, temporal and fusiform gyri, which consistently enabled infected patients to be distinguished from healthy controls [ 44 ].…”

Cortical Grey Matter Volume Loss links to Neurological Sequelae in post COVID-19 “Long Haulers”

“…GM changes in long COVID have also been documented using 18 fluorodeoxyglucose Positron Emission Tomography (PET) with decreases in metabolic activity among 28 consecutive outpatients, identified mainly in the right frontal and temporal lobes, but including orbitofrontal cortex and internal temporal and frontoparietal lobes [42]. Other studies involve decreases in cingulate cortex [43], or bilateral rectus/orbital gyrus including the olfactory gyrus, pre and post central, temporal and fusiform gyri, which consistently enabled infected patients to be distinguished from healthy controls [44].…”