Structural and metabolic brain abnormalities in COVID-19 patients with sudden loss of smell

Abstract

Objectives: Sudden loss of smell is a very common symptom of coronavirus disease 19 (COVID-19). This study characterizes the structural and metabolic cerebral correlates of dysosmia in patients with COVID-19.

Methods: Structural brain magnetic resonance imaging (MRI) and positron emission tomography with [18F]-fluorodeoxyglucose (FDG-PET) were prospectively acquired simultaneously on a hybrid PET-MR in 12 patients (2 males, 10 females, mean age: 42.6 years, age range: 23-60 years) with sudden dysosmia and positive detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on nasopharyngeal swab specimens. FDG-PET data were analyzed using a voxel-based approach and compared with that of a group of healthy subjects.

Results: Bilateral blocking of the olfactory cleft was observed in six patients, while subtle olfactory bulb asymmetry was found in three patients. No MRI signal abnormality downstream of the olfactory tract was observed. Decrease or increase in glucose metabolism abnormalities was observed (p < .001 uncorrected, k ≥ 50 voxels) in core olfactory and high-order neocortical areas. A modulation of regional cerebral glucose metabolism by the severity and the duration of COVID-19-related dysosmia was disclosed using correlation analyses.

Conclusions: This PET-MR study suggests that sudden loss of smell in COVID-19 is not related to central involvement due to SARS-CoV-2 neuroinvasiveness. Loss of smell is associated with subtle cerebral metabolic changes in core olfactory and high-order cortical areas likely related to combined processes of deafferentation and active functional reorganization secondary to the lack of olfactory stimulation.

Keywords: COVID-19; FDG-PET; MRI; Smell loss.

Fig. 1

Axial T2-weighted coronal images demonstrating bilateral and complete obliteration of the olfactory clefts (white single arrows) with (a) no associated olfactory bulb asymmetry and with (b) asymmetry of the olfactory bulbs (left (L) bulb relatively enlarged, white double arrow). The criblate plate is illustrated by the dotted line

Fig. 2

Left: regional hyper- (red to white color scale) and hypo- (blue to white color scale) metabolism in two typical patients rendered on a 3D canonical brain. Images are thresholded at p < .001 uncorrected (k ≥ 50 voxels). Right: native FDG-PET images co-registered on the patients’ 3D T1 MRI sequence. White arrows point towards the brain areas showing significant metabolic changes at the uncorrected statistical threshold illustrated on the left part of the figure

Fig. 3

Regional cerebral glucose metabolic abnormalities observed at the group level. Legend: regional hypometabolism (top) and hypermetabolism (bottom) observed at the group level. Images are thresholded at p < .001 uncorrected (k ≥ 50 voxels)

Fig. 4

Results of the correlation analyses performed between the cerebral glucose metabolism and the severity of olfactory dysfunction and between the cerebral glucose metabolism and the duration of anosmia. (a) Regression plots of the severity of olfactory dysfunction assessed by the identification test score (Top) and adjusted metabolic responses obtained by considering the peak voxel in the right FEF ([30 6 48], Pearson’s correlation: r = 0.97, p < .001) and in the left orbitofrontal cortex ([− 12 68 0], Pearson’s correlation: r = 0.94, p < .001). (b) Regression plots of the duration of anosmia (Bottom) and adjusted metabolic responses obtained by considering the peak voxel in the right DLPFC ([38 32 34], Pearson’s correlation: r = 0.94, p < .001) and in the right orbitofrontal cortex ([34 32 − 10], Pearson’s correlation: r = 0.9, p < .001)