Metabolic correlates of olfactory dysfunction in COVID-19 and Parkinson's disease (PD) do not overlap

Abstract

Purpose: Hyposmia is a common feature of COVID-19 and Parkinson's disease (PD). As parkinsonism has been reported after COVID-19, a link has been hypothesized between SARS-CoV2 infection and PD. 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-naïve PD patients.

Methods: Forty-four patients who experienced hyposmia after SARS-COV2 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 the 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 COVID-hyposmia, 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 the 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).

Conclusion: 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.

Keywords: Anosmia; Brain PET; COVID-19; Parkinson’s disease; [18F]FDG.

Fig. 1

A, B Schematic representation of the steps that narrowed post-COVID and de novo PD subgroups to the final number of patients

Fig. 2

Correlation between Sniffin-test scores and whole-brain metabolism in COVID-hyposmia (A) and PD-hyposmia patients (B). A significant direct correlation was highlighted between olfaction and brain metabolism in rectus, middle temporal, and medial frontal gyri on both hemispheres and in the right precentral gyrus and anterior cingulate in COVID-hyposmia patients and in cuneus/precuneus on both hemispheres and in the lateral occipital cortex in the left hemisphere in PD-hyposmia patients. Clusters with significant hypometabolism are shown superimposed on an MRI template. The color bars indicate the level of z-scores for significant voxels. (See Table 2 for details on coordinates and z-scores.)

Fig. 3

A, B Results of the ANOVA statistical model comparing the three groups of patients (COVID-hyposmia, COVID-non-hyposmia, and PD-hyposmia) with age and sex as nuisance variables. Clusters with significant hypometabolism are shown superimposed on a 3D brain rendering. Direct comparison between patients subgroups was explored in the post hoc analyses (Fig. 4A–C)

Fig. 4

Comparisons between COVID-hyposmia on one side and COVID-non-hyposmia and PD-hyposmia respectively. COVID-hyposmia patients showed significant hypometabolism with respect to COVID-non-hyposmia in a bilateral and symmetric cluster encompassing gyrus rectus and inferior, middle, and superior frontal gyrus (A) while (changing the direction of the contrast) no regions of significant hypometabolism were identified in COVID-non-hyposmia. With respect to PD-hyposmia patients COVID-hyposmia patients showed hypometabolism in middle and superior temporal gyri, medial, and middle frontal gyri on both hemispheres and right insula (B). PD-hyposmia patients showed relative hypometabolism with respect to COVID-hyposmia in wide cortical regions mainly involving inferior and middle occipital gyri and cuneus in both hemispheres (C). Clusters with significant hypometabolism are shown superimposed on an MRI template. The color bars indicate the level of z-scores for significant voxels. (See Tables 3 and 4 for details on coordinates and z-scores.)