MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms

Abstract

Background and objective Despite olfactory disorders being among the most common neurological complications of coronavirus disease 2019 (COVID-19), their pathogenesis has not been fully elucidated yet. Brain MR imaging is a consolidated method for evaluating olfactory system’s morphological modification, but a few quantitative studies have been published so far. The aim of the study was to provide MRI evidence of olfactory system alterations in patients with COVID-19 and neurological symptoms, including olfactory dysfunction. Methods 196 COVID-19 patients (median age: 53 years, 56% females) and 39 controls (median age 55 years, 49% females) were included in this cross-sectional observational study; 78 of the patients reported olfactory loss as the only neurological symptom. MRI processing was performed by ad-hoc semi-automatic processing procedures. Olfactory bulb (OB) volume was measured on T2-weighted MRI based on manual tracing and normalized to the brain volume. Olfactory tract (OT) median signal intensity was quantified on fluid attenuated inversion recovery (FLAIR) sequences, after preliminary intensity normalization. Results COVID-19 patients showed significantly lower left, right and total OB volumes than controls ( p < 0.05). Age-related OB atrophy was found in the control but not in the patient population. No significant difference was found between patients with olfactory disorders and other neurological symptoms. Several outliers with abnormally high OT FLAIR signal intensity were found in the patient group. Conclusions Brain MRI findings demonstrated OB damage in COVID-19 patients with neurological complications. Future longitudinal studies are needed to clarify the transient or permanent nature of OB atrophy in COVID-19 pathology. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s00415-023-11561-0.

Cognitive and functional connectivity impairment in post-COVID-19 olfactory dysfunction

“…It may involve disrupting the olfactory system at different levels, from the sensory epithelium located in the olfactory clefts to olfactory neurons in the olfactory bulb and olfactory cortices ( Xydakis et al, 2021 ). Previous magnetic resonance imaging (MRI) studies revealed a variety of abnormalities of both peripheral and central olfactory areas, including olfactory cleft obstruction, abnormalities in olfactory bulb signal intensity and atrophy, and, notably, neurodegenerative changes in the limbic structures involved in the processing of olfactory stimuli and cognitive functions, also in patients with persistent OD ( Kandemirli et al, 2021 , Keshavarz et al, 2021 , Yildirim et al, 2022 , Douaud et al, 2022 , Capelli et al, 2023 ). Task-based olfactory functional MRI (fMRI) in COVID-19-related OD revealed absent activation of the orbitofrontal cortex and a more robust activation in the trigeminosensory activity ( Yildirim et al, 2022 , Ismail and Gad, 2021 ).…”

A Comprehensive Review of COVID-19-Related Olfactory Deficiency: Unraveling Associations with Neurocognitive Disorders and Magnetic Resonance Imaging Findings

“…For the OS depth, no significant difference was found between the two groups for Yildirim et al [35]. Capelli et al [2] also showed significantly lower left, right, and total OBV in COVID-19 patients (196 patients of which 78 reported olfactory loss as the only neurological symptom) compared to 39 controls. They processed MRI images by ad hoc semi-automatic processing procedures.…”

“…Kandermirli et al [39] highlighted that 91.3% of cases with persistent COVID-19-related OD had abnormalities in the form of a diffusely increased OB signal intensity. Capelli et al [2] quantified, on 3D T2 FLAIR sequences, the OT median signal intensity, but no significant evidence was found in the COVID-19 patient group compared with control subjects, except for a few outliers. Li et al [44], in a case report, reported a 21-year-old male who had presented with a loss of smell for five days without any respiratory problems or fever and revealed hyperintensities inside bilateral olfactory nerves, suggestive of bilateral olfactory neuropathy beyond a smaller right OB.…”

“…COVID-19 can present with a wide range of respiratory and extra-respiratory symptoms, including a broad spectrum of acute neurological symptoms involving both the central and peripheral nervous systems, such as headaches, dizziness, Diagnostics 2024, 14, 359 2 of 18 olfactory and gustatory deficits, polyneuropathies, and even encephalitis or strokes. Some studies have highlighted how neurological sequelae are present in a third of patients in the first six months following acute COVID-19 infection [2][3][4].…”

“…Olfactory and gustative dysfunctions can manifest in various ways among COVID-19 patients, ranging from a complete loss of perception (anosmia and ageusia) to reduced perception (hyposmia and hypogeusia) and even distorted perception (parosmia and parageusia). In some cases, individuals may experience sensations without external stimuli, referred to as phantosmia and phantogeusia [2,6,7].…”