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.
ABSTRACT
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.