A Systematic Review of Imaging Studies in Olfactory Dysfunction Secondary to COVID-19

Abstract

Rationale and Objectives Hyposmia/anosmia is common among patients with COVID-19. Various imaging modalities have been used to assess olfactory dysfunction in COVID-19. In this systematic review, we sought to categorize and summarize the imaging data in COVID-19-induced anosmia. Material and Methods Eligible articles were included after a comprehensive review using online databases including Google scholar, Scopus, PubMed, Web of science and Elsevier. Duplicate results, conference abstracts, reviews, and studies in languages other than English were excluded. Results In total, 305 patients undergoing MRI/functional MRI (177), CT of paranasal sinuses (129), and PET/CT or PET/MRI scans ( 14 ) were included. Out of a total of 218 findings reported on MRI, 80 were reported on early (≤ 1 month) and 85 on late (> 1 month) imaging in relation to the onset of anosmia. Overall, OB morphology and T2-weighted or FLAIR signal intensity were normal in 68/218 (31.2%), while partial or complete opacification of OC was observed in 60/218 (27.5%). T2 hyperintensity in OB was detected in 11/80 (13.75%) and 18/85 (21.17%) on early and late imaging, respectively. Moreover, OB atrophy was reported in 1/80 (1.25%) on early and in 9/85 (10.58%) on late imaging. Last, among a total of 129 CT scans included, paranasal sinuses were evalualted in 88 (68.21%), which were reported as normal in most cases (77/88, [87.5%]). Conclusion In this systematic review, normal morphology and T2/FLAIR signal intensity in OB and OC obstruction were the most common findings in COVID-19-induced anosmia, while paranasal sinuses were normal in most cases. OC obstruction is the likely mechanism for olfactory dysfunction in COVID-19. Abnormalities in OB signal intensity and OB atrophy suggest that central mechanisms may also play a role in late stage in COVID-19-induced anosmia.

Transient modifications of the olfactory bulb on MR follow-up of COVID-19 patients with related olfactory dysfunction

“…Eliezer et al 16 found that OD and OC obstruction are present at the early stage of the disease, and improved both at one-month follow-up, suggesting that OD in Covid-19 patients was caused, at least in part, by reversible inflammatory changes in the OC. In a recent systematic review 17 , opacification of OC (60/218 - 27.5%) together with normal OB morphology and signal intensity (68/218 - 31.2%) were the most common imaging findings in patients with olfactory dysfunction secondary to COVID-19. In our study, we found only partial OC obstruction in only 4/11 patients on the initial MRI, totally regressive during follow-up, explaining only partly OD.…”

Oral SARS-CoV-2 Inoculation Causes Nasal Viral Infection Leading to Olfactory Bulb Infection: an Experimental Study

“…In human studies, SARS-CoV-2 has been detected in the OB of autopsied cases 40,41 . Imaging studies have also shown hyperintensity of the OB on T2 uid-attenuated inversion recovery magnetic resonance images 15,42 and a pattern of hypometabolism involving the olfactory system (orbitofrontal cortex and olfactory and rectus gyri) on positron emission tomography of brain 43 . A study on rhesus monkeys reported that SARS-CoV-2 primarily invades the central nervous system via the OB 39 .…”

“…Therefore, the nasal and oral cavities are considered the major routes of SARS-CoV-2 infection. Although the mechanisms underlying olfactory dysfunction related to COVID-19 have been gradually elucidated through histological and genomic examinations 7,11−13 and imaging studies 14,15 , it remains di cult to disentangle the involved mechanisms because of the heterogeneity of presentations 16 . Currently, the following mechanisms are being considered: 1) transient conductive olfactory dysfunction resulting from airway blockage due to local in ammation and edema of the nasal mucosa in the olfactory cleft and nasal passages; 2) temporary sensorineural olfactory dysfunction due to damage to supporting tissues such as the sustentacular cells, Bowman's gland, and microvillar cells, excluding mature olfactory receptor cells (ORNs); 3) chronic or permanent sensorineural olfactory dysfunction due to damage to the ORNs; 4) central olfactory dysfunction due to SARS-CoV-2 infection of the olfactory bulb (OB) and olfactory cortex [16][17][18] .…”

Oral SARS-CoV-2 Inoculation Causes Nasal Viral Infection Leading to Olfactory Bulb Infection: An Experimental Study

“…Therefore, the nasal and oral cavities are considered to be the major routes of SARS-CoV-2 infection. Although the mechanisms underlying olfactory dysfunction related to COVID-19 have been gradually elucidated through histological and genomic examinations ( Singh et al., 2020 ; Butowt and von Bartheld, 2021 ; Sato et al., 2021 ; Ueha et al., 2021 ) and imaging studies ( Naeini et al., 2020 ; Keshavarz et al., 2021 ), it remains difficult to disentangle the involved mechanisms because of the heterogeneity of presentations ( Xydakis et al., 2021 ). Currently, the following mechanisms are being considered: 1) transient conductive olfactory dysfunction resulting from airway blockage due to local inflammation and edema of the nasal mucosa in the olfactory cleft and nasal passages; 2) temporary sensorineural olfactory dysfunction due to damage to supporting tissues such as the sustentacular cells, Bowman’s gland, and microvillar cells, excluding mature olfactory receptor cells (ORNs); 3) chronic or permanent sensorineural olfactory dysfunction due to damage to the ORNs; 4) central olfactory dysfunction due to SARS-CoV-2 infection of the olfactory bulb (OB) and olfactory cortex ( Xydakis et al., 2021 ; Ye et al., 2021 ; Zhang et al., 2021 ).…”