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Aim/Introduction: A recent report prepared by the Centers for Disease Control and Prevention indicates that 71% of patients experience persistent fatigue even after recovery from the acute phase of COVID-19 infection. We investigated if post-COVID-19 fatigue is associated with alterations in brain metabolism and microstructure to better understand the underlying neurobiological mechanism. Material(s) and Method(s): Brain F-18 FDG PET and diffusion tensor magnetic resonance imaging (DTIMR) were performed in 12 patients experiencing persistent post- COVID-19 fatigue that lasted more than six weeks post-discharge from hospitalization or discontinued home isolation after acute SARS-CoV-2 infection (fatigue group, Male:Female = 6:6, mean > SD age 35.7 > 13.8 years, Chalder fatigue scale score 8.3 > 2.2, time since COVID-19 diagnosis 7.9 > 5.5 months) and 9 recovered patients without such fatigue (non-fatigue group, M:F = 3:6, age 25.6 > 9.2, fatigue score 1.6 > 1.5, time since COVID-19 diagnosis 8.0 > 6.0 months). A commercially available normative brain FDG PET database (MIMneuro, v7.0.5, MIM Software, Inc.) was used to derive z scores for regional cerebral glucose metabolism. Fractional anisotropy (FA) values were extracted from DTI-MR datasets. Twotailed t-tests were performed for group comparison and P < 0.05 was considered statistically significant. Result(s): The fatigue group demonstrated significantly higher regional cerebral glucose metabolism in the left inferior and middle cerebellar peduncle (P = 0.001 and 0.043, respectively), left middle temporal gyrus (P = 0.002), left parahippocampal gyrus (P = 0.029), primary visual cortex (P = 0.031), supplementary motor area (P = 0.036), supramarginal gyrus (P = 0.044), and lower metabolism in the left precentral gyrus (P = 0.001) when compared to the non-fatigue group. The fatigue group also demonstrated significantly higher FA values in the left and right middle frontal gyrus (P = 0.014 and 0.038, respectively), left precentral gyrus (P = 0.024), right superior frontal gyrus (P =0.032), right postcentral gyrus (P = 0.047), left superior parietal gyrus (P = 0.048), and corpus callosum (P = 0.016) when compared to the nonfatigue group. Conclusion(s): Patients experiencing persistent fatigue after recovering from acute SARS-CoV-2 infection demonstrated significant changes in regional cerebral glucose metabolism and microstructure, when compared to those individuals without on-going fatigue symptoms. The altered cerebral metabolic and microstructural profile may help to better understand the neurobiological mechanism for management of patients suffering from lingering post-COVID-19 fatigue.
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BACKGROUND: Common long-term sequelae after COVID-19 include fatigue and cognitive impairment. Although symptoms interfere with daily living, the underlying pathology is largely unknown. Previous studies report relative hypometabolism in frontal, limbic and cerebellar regions suggesting focal brain involvement. We aimed to determine whether absolute hypometabolism was present and correlated to same day standardized neurocognitive testing. METHODS: Fourteen patients included from a long COVID clinic had cognitive testing and quantitative dynamic [18F]FDG PET of the brain on the same day to correlate cognitive function to metabolic glucose rate. RESULTS: We found no hypometabolism in frontal, limbic and cerebellar regions in cognitively impaired relative to cognitive intact patients. In contrast, the cognitive impaired patients showed higher cerebellar metabolism (p = 0.03), which correlated with more severe deficits in working memory and executive function (p = 0.03). CONCLUSIONS: Hypermetabolism in the cerebellum may reflect inefficient brain processing and play a role in cognitive impairments after COVID-19.
ABSTRACT
Aim/Introduction: A recent report prepared by the Centers for Disease Control and Prevention indicates that 71% of patients experience persistent fatigue even after recovery from the acute phase of COVID-19 infection. We investigated if post-COVID-19 fatigue is associated with alterations in brain metabolism and microstructure to better understand the underlying neurobiological mechanism. Material(s) and Method(s): Brain F-18 FDG PET and diffusion tensor magnetic resonance imaging (DTIMR) were performed in 12 patients experiencing persistent post- COVID-19 fatigue that lasted more than six weeks post-discharge from hospitalization or discontinued home isolation after acute SARS-CoV-2 infection (fatigue group, Male:Female = 6:6, mean > SD age 35.7 > 13.8 years, Chalder fatigue scale score 8.3 > 2.2, time since COVID-19 diagnosis 7.9 > 5.5 months) and 9 recovered patients without such fatigue (non-fatigue group, M:F = 3:6, age 25.6 > 9.2, fatigue score 1.6 > 1.5, time since COVID-19 diagnosis 8.0 > 6.0 months). A commercially available normative brain FDG PET database (MIMneuro, v7.0.5, MIM Software, Inc.) was used to derive z scores for regional cerebral glucose metabolism. Fractional anisotropy (FA) values were extracted from DTI-MR datasets. Twotailed t-tests were performed for group comparison and P < 0.05 was considered statistically significant. Result(s): The fatigue group demonstrated significantly higher regional cerebral glucose metabolism in the left inferior and middle cerebellar peduncle (P = 0.001 and 0.043, respectively), left middle temporal gyrus (P = 0.002), left parahippocampal gyrus (P = 0.029), primary visual cortex (P = 0.031), supplementary motor area (P = 0.036), supramarginal gyrus (P = 0.044), and lower metabolism in the left precentral gyrus (P = 0.001) when compared to the non-fatigue group. The fatigue group also demonstrated significantly higher FA values in the left and right middle frontal gyrus (P = 0.014 and 0.038, respectively), left precentral gyrus (P = 0.024), right superior frontal gyrus (P =0.032), right postcentral gyrus (P = 0.047), left superior parietal gyrus (P = 0.048), and corpus callosum (P = 0.016) when compared to the nonfatigue group. Conclusion(s): Patients experiencing persistent fatigue after recovering from acute SARS-CoV-2 infection demonstrated significant changes in regional cerebral glucose metabolism and microstructure, when compared to those individuals without on-going fatigue symptoms. The altered cerebral metabolic and microstructural profile may help to better understand the neurobiological mechanism for management of patients suffering from lingering post-COVID-19 fatigue.
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Aim/Introduction: In SARS-CoV2 outbreak scenario, many considerations about possible long-term effects of this infection can be made. Early evidences reported in literature about the relation between long-COVID disease and brain involvement in patients with persistent neurological symptoms, found brain hypometabolism on 18F-FDG PET/CT. Our study aims to evaluate the impact of SARSCoV2 infection on brain metabolism in a long-term setting, also in asymptomatic patients. Material(s) and Method(s): Brain PET scans of 48 patients with documented previous SARS-CoV2 infection (COVID-group), performed from January to December 2021, were analysed and compared with brain PET scans of 48 patients, controlled for age and sex, who didn't experience the infection (control-group) using a quantitative software-aided approach. Patients with documented brain metastases or neurodegenerative diseases were excluded. No patient had neurological symptoms at the time of PET. CortexID Suite software (GE Healthcare) was applied for a segmentation analysis reporting Z score (ZS) values for each brain area in both groups. Basing on hypometabolism severity, the sample was divided as follows: normal (>=-1 ZS), mild (between -1 and -2 ZS), severe (<=-2 ZS). For COVID-group, time intercurred from infection to PET was recorded. Differences between ZS per areas between the two groups were evaluated using Mann-Withney-U test. Considering hypometabolism severity, Chi-Square test was applied to evaluate differences between groups. Finally, Pearson's test was used to correlate COVID-group ZS and time intercurred from infection. Result(s): Mean age of patients was 63.2 and 63.6 years old in the COVID-and control-group respectively. In both groups, 22/48 were male. In COVID-group 27/48 patients have had symptoms (cough, fever, dyspnoea) during SARS-CoV2 infection. The majority of brain areas showed a statistically significant difference in ZS values between groups. According to hypometabolism severity, left pre-frontal medial (p=0.032), right sensory-motor (p=0.014), right inferior parietal (p=0.001) and right lateral temporal (p=0.002) areas showed a statistically significant difference between COVIDand control-group with a prevalence in COVID-group of mild and severe brain hypometabolism. Lower ZS values were observed in patients with a longer time intercurred from infection to PET/CT scan. Conclusion(s): Our preliminary results confirm the impact of SARS-CoV2 infection on brain metabolism, consisting mostly in a mild hypometabolism. The presence of this metabolic pattern in patients without neurological symptoms suggests a devious action of the infection. Further studies, also using serial PET, are necessary to explore whether these metabolic alterations are transient or predictive of a future clinical manifestation.
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Aim/Introduction: Neurological sequelae of Covid-19 have been widely documented by anatomic and functional methods [1,2]. Brain metabolism studies using 18F-FDG PET/CT during the subacute phase of the disease have also been published [1]. On the other hand, there is a lack of information about the influence of SARS-Cov2 infection on brain metabolism during the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism during the acute onset of Covid-19. Material(s) and Method(s): We studied 23 patients (13 women, median age 55.5[33-78] years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for Covid-19 and requiring supplemental oxygen. Dedicated PET/CT images of the brain were acquired for 10 minutes, 1h after injection of 4.4 MBq/kg of 18F-FDG. Visual analysis was performed by two nuclear medicine specialists and one radiologist. Quantitative analysis was performed using dedicated software. 18F-FDG uptake in multiple brain regions was evaluated and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with a group of normal subjects. More than 2 SD above or below the control group was considered significant in each area. Result(s): Serum C-reactive protein at admission ranged from 6.43 to 189.0 mg/L (mean 97.0 +/- 55.5 mg/L). The mean supplemental oxygen demand was 2.8 +/- 1.5 L/min. PET/CT images were acquired between 4 and 20 days of symptoms (mean 12.9 +/- 3.8 days). The images showed increased glycolytic metabolism in basal ganglia and relatively reduced brain metabolism in cortical regions. Basal ganglia metabolism was bilaterally increased in 18/23 (78.3%) and normal in 5 (21.7%) patients. Lenticular nucleus presented increased metabolism in 21/23 (91.3%) and was normal in 2 (8.7%) patients. Frontal and parietal lobes metabolism was respectively reduced in 9/24 (37.6%) and 8/23 (34.8%) patients. The whole brain metabolism was normal in 20/23 (86.9%) patients. Olfactory cortex metabolism was normal in 18/23 (78.3%) patients. Conclusion(s): Brain metabolism is clearly affected during the acute phase of SARS-Cov2 infection. The most frequent finding was increased basal ganglia metabolism, with most patients presenting marked lenticular nucleus hypermetabolism. Frontal and parietal lobes presented reduced metabolism in some patients. Interestingly, olfactory cortex is not affected in most patients, suggesting that anosmia, reported by some patients, is not related to the direct involvement of the brain by the disease.
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Background-Aim: While a frontal dysfunction is reported in post- SARS-CoV-2 with neurological symptoms (neuro-SARS-CoV-2), it is unclear whether this brain vulnerability is long lasting or reversible. The present study evaluated brain dysfunctions-as measured by FDG-PET-in neuro-SARS-CoV-2 over time to provide a better understanding of physiopathology underlying central nervous system involvement. Methods: 26 patients with neuro-SARS-CoV-2 were included. Seven patients were in the acute, the others in the sub-acute and chronic phase, namely, four at 1-month, four at 2-months, four at 3-months, four at 5 months and four at 7-9-months after onset. Patients underwent FDG-PET exams, clinical and cognitive evaluations. One patient was evaluated longitudinally, during the acute phase, and at a 5-months follow-up. Brain metabolism was analysed at the singlesubject and group levels by a comparisons with healthy controls. Correlations between severity/extent of hypometabolism and clinical variables of interest (global cognitive cognition, blood oxygen level saturation, and inflammatory status -C-reactive protein measurements) were also assessed. Results: Patients with acute neuro-SARS-CoV-2 showed the most severe and diffuse cortical hypometabolism, affecting almost all cortical areas. 2-months after the acute infection, a significant decrease in hypometabolism extension emerged, affecting mainly the frontal and temporal cortex. At 5-months after the acute phase, a recovery of cortical hypometabolism was evident, with limited residual clusters in frontal regions. At 7-9-months, no regions with brain hypometabolism were present. The only patient evaluated longitudinally showed a significant brain metabolic improvement from the acute phase (with diffuse cortical hypometabolism) to a 5-months follow-up (brain hypometabolism limited to frontal areas). Of note, the extent and severity of hypometabolism were associated with severe global cognitive dysfunctions, low blood oxygen level saturation, and high inflammatory status in all patients. Conclusions: These findings suggest that cortical functional impairment observed in patients with neuro-SARS-CoV-2 infection is likely to be transient and almost reversible, possibly due to synergistic effects of systemic virus-mediated inflammation sustained by systemic cytokine release and transient hypoxia inducing reversible neural dysfunction and local microglial activation.
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Background-Aim: A potential link has been investigated between hyposmia after COVID-19 and an increased risk to develop neurological long-term sequelae also in patients who experienced mild or moderate disease. Hyposmia is a common feature PD and parkinsonism has been reported after COVID-19 suggesting a potential link between SARS-CoV2 infection and PD. [18F]FDG PET may represent a suitable tool to capture potential common metabolic signature of hyposmia after COVID-19 and in PD patients. We aimed to evaluate brain metabolic correlates of isolated persistent hyposmia after mild-to-moderate COVID-19 and to compare them with metabolic signature of hyposmia in drug-naive PD patients. Methods: Forty-four patients who experienced hyposmia after SARSCOV2 infection underwent brain [18F]FDG-PET in the first 6 months after recovery. Olfaction was assessed by means of the 16-item ''Sniffin-Sticks'' test and patients were classified as with or without persistent hyposmia (COVID-hyposmia and COVID-no-hyposmia respectively). Brain [18F]FDG-PET of post-COVID subgroups were compared in SPM12. COVID-hyposmia patients were also compared with eighty-two drug-naïve PD patients with hyposmia. Multiple-regression- analysis was used to identify correlations between olfactory test-scores and brain metabolism in patients' subgroups. Results: COVID-hyposmia patients (n = 21) exhibited significant hypometabolism in bilateral gyrus rectus and orbitofrontal cortex with respect to COVID-non-hyposmia (n = 23) (p<0.002) and in middle and superior temporal gyri, medial/middle frontal gyri and right insula with respect to PD-hyposmia (p<0.012). With respect to COVIDhyposmia, PD-hyposmia patients showed hypometabolism in inferior/ middle occipital gyri and cuneus bilaterally. Olfactory test-scores were directly correlated with metabolism in bilateral rectus and medial frontal gyri and in right middle temporal and anterior-cingulate gyri in COVID-hyposmia patients (p<0.006) and with bilateral cuneus/precuneus and left lateral occipital-cortex in PD-hyposmia patients (p<0.004). Conclusions: Metabolic signature of persistent hyposmia after COVID-19 encompasses cortical regions involved in olfactory perception and does not overlap metabolic correlates of hyposmia in PD. An impairment in olfactory judgement seem to underlie hyposmia in PD patients while a more restricted perception deficit seems to explain hyposmia in COVID-19. The potential long term neurological sequelae of COVID-19 are of interest from the clinical and economical point of view. Studies targeting symptoms common to COVID-19 and chronic neurological diseases and aiming to explore potential common pathways are of interest also to avoid unjustified claims about a future high incidence of neurodegenerative diseases secondary to the SARS-CoV-2 pandemic.
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This study aims to evaluate the impact of French national lockdown of 55 days on brain metabolism of patients with neurological disorders. Whole-brain voxel-based PET analysis was used to correlate 18 F-FDG metabolism to the number of days after March 17, 2020 (in 95 patients; mean age: 54.3 years ± 15.7; 59 men), in comparison to the same period in 2019 before the SARS-CoV-2 outbreak (in 212 patients; mean age: 59.5 years ± 15.8; 114 men), and to the first 55 days of deconfinement (in 188 patients; mean age: 57.5 years ± 16.5; 93 men). Lockdown duration was negatively correlated to the metabolism of the sensory-motor cortex with a prevailing effect on the left dominant pyramidal tract and on younger patients, also including the left amygdala, with only partial reversibility after 55 days of deconfinement. Weak overlap was found with the reported pattern of hypometabolism in long COVID (<9%). Restriction of physical activities, and possible related deconditioning, and social isolation may lead to functional disturbances of sensorimotor and emotional brain networks. Of note, this metabolic pattern seems distinct to those reported in long COVID. Further longitudinal studies with longer follow-up are needed to evaluate clinical consequences and relationships on cognitive and mental health against functional deactivation hypothesis, and to extend these findings to healthy subjects in the context of lockdown.