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.
ABSTRACT
Background and aims: Coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection has been associated with a number of neurological complications, including persistent hyposmia. Despite its relative frequency the neural bases of hyposmia post-SARS-Cov2 infection are to date poorly understood. Methods: 22 patients (12 males and 10 females;mean age 64±10.5 years, range 35-79) underwent whole-body [18] F-FDG-PET including a dedicated brain acquisition following their recovery after SARS-CoV-2 infection. Patients that previously required mechanic ventilation or showed severe respiratory distress syndrome due to SARSCoV- 2 infection were excluded given the potential independent effect of these clinical scenarios on brain metabolism. Among the enrolled patients, presence of isolated persistent hyposmia, as assessed with the smell diskettes olfaction test, was shown in fourteen subjects. A voxelwise analysis was used to identify brain regions of relative hypomebolism in hyposmic patients compared to a group of 61 age- and sex-matched healthy controlsStructural connectivity of these regions was assessed with the BCB toolkit. Results: Relative hypometabolism was demonstrated in bilateral parahippocampal and fusiform gyri and in left insula in hyposmic patients with respect to controls. Structural connectivity maps showed the involvement of the bilateral longitudinal fasciculi. Conclusion: Here we provide the first evidence of cortical hypometabolism in patients with isolated persistent hyposmia after SARS-CoV-2 infection without an history of severe respiratory distress. [18]F-FDG-PET may play a role in the identification of long-term brain functional sequelae of COVID-19.