Neuroradiological Basis of COVID‐19 Olfactory Dysfunction: A Systematic Review and Meta‐Analysis

Abstract

Objective Olfactory dysfunction (OD) is a common presenting symptom of COVID‐19 infection. Radiological imaging of the olfactory structures in patients with COVID‐19 and OD can potentially shed light on its pathogenesis, and guide clinicians in prognostication and intervention. Methods PubMed, Embase, Cochrane, SCOPUS were searched from inception to August 1, 2021. Three reviewers selected observational studies, case series, and case reports reporting radiological changes in the olfactory structures, detected on magnetic resonance imaging, computed tomography, or other imaging modalities, in patients aged ≥18 years with COVID‐19 infection and OD, following preferred reporting items for systematic reviews and meta‐analyses guidelines and a PROSPERO‐registered protocol (CRD42021275211). We described the proportion of radiological outcomes, and used random‐effects meta‐analyses to pool the prevalence of olfactory cleft opacification, olfactory bulb signal abnormalities, and olfactory mucosa abnormalities in patients with and without COVID‐19‐associated OD. Results We included 7 case–control studies (N = 353), 11 case series (N = 154), and 12 case reports (N = 12). The pooled prevalence of olfactory cleft opacification in patients with COVID‐19 infection and OD (63%, 95% CI = 0.38–0.82) was significantly higher than that in controls (4%, 95% CI = 0.01–0.13). Conversely, similar proportions of cases and controls demonstrated olfactory bulb signal abnormalities (88% and 94%) and olfactory mucosa abnormalities (2% and 0%). Descriptive analysis found that 55.6% and 43.5% of patients with COVID‐19 infection and OD had morphological abnormalities of the olfactory bulb and olfactory nerve, respectively, while 60.0% had abnormal olfactory bulb volumes. Conclusion Our findings implicate a conductive mechanism of OD, localized to the olfactory cleft, in approximately half of the affected COVID‐19 patients. Laryngoscope, 132:1260–1274, 2022

Prognosis and persistence of smell and taste dysfunction in patients with covid-19: meta-analysis with parametric cure modelling of recovery curves

“…Sensorineural mechanisms are currently thought to be the predominant mechanism of covid-19 related smell dysfunction, 54 55 although conductive mechanisms have been implicated too. 56 SARS-CoV-2 infects and eliminates most olfactory epithelial support (sustentacular) cells that express angiotensin converting enzyme-2, which leads to olfactory neuron deciliation and necrosis. 55 57 Varying regeneration speed of support cells and sensory neurons, influenced by the degree of inflammation, could explain the delayed smell recovery.…”

Olfactory system measurements in COVID-19: a systematic review and meta-analysis

“…Furthermore, increased T2 FLAIR signal intensity of OB has been detected in COVID-19-related OD compared to non-COVID-19 anosmic controls by a recent study [ 29 ]. A recent meta-analysis showed that 88% of patients with OD due to COVID-19 had signal abnormalities in OB, which were not significantly different from controls (94%) [ 9 ]. It can be speculated that diversity in the results stems from the methodological differences in the studies, especially the applied field of strength and the time of imaging regarding the disease phase [ 44 ].…”

“…Previous studies have demonstrated the high presence of ACE2 and TMPRSS2 in the OC region, especially supporting (sustentacular) cells of the olfactory epithelium rather than olfactory neurons [ 10 ]. A recent systematic review of 30 studies showed a pooled prevalence of 63% (95% CI, 0.38 to 0.82) for OC opacification in CT or MR imaging of COVID-19 patients with OD, which was significantly higher than the controls with 4% (95% CI, 0.01 to 0.13) [ 9 ].…”

“…A recent systematic review showed a significantly higher prevalence of OC opacification in patients with COVID-19 infection than in controls. Several studies have also reported other findings, such as alterations in OB volume, OC volume, OS depth, and olfactory nerve morphology [ 9 ].…”

The burden of prolonged smell and taste loss in covid-19

“…In fact, smell and taste loss are common complaints among patients with covid-19, with an estimated 50% of patients reporting these symptoms 1. This is thought to occur due to conductive barriers and nerve damage from the extensive inflammation in covid-19 infection 2345…”