Clinical and Imaging Evaluation of COVID-19-Related Olfactory Dysfunction

The coronavirus disease 2019 (COVID-19) pandemic highlighted the association between SARS-CoV-2 infection and chemosensory dysfunction, particularly olfactory dysfunction (OD), including anosmia (loss of smell) and hyposmia (reduced smell). Initial screening focused on fever, respiratory distress, and cough, but OD emerged as a significant, sometimes sole, presenting symptom. OD can be classified as conductive (due to nasal airflow impairment) or sensorineural (due to olfactory epithelium or central pathway dysfunction). While conductive loss is often reversible, sensorineural loss is more concerning. Post-viral anosmia can result from nasal obstruction or neurological viral spread through the olfactory cleft (OC) mucosa. In COVID-19, OD often occurs without associated nasal symptoms, suggesting a different pathophysiology than obstructive causes. The exact pathophysiology remains unclear, but sensorineural loss, possibly due to olfactory bulb (OB) damage, is a leading hypothesis. Changes in olfactory neuron calcium levels have also been implicated. Magnetic resonance imaging (MRI) of the olfactory pathway is valuable in evaluating OD. Previous studies using MRI have reported abnormal OB volume and signal intensity in COVID-19-related OD, supporting the theory of viral invasion via olfactory pathways causing neural structure damage. This study aimed to analyze clinical and imaging findings in COVID-19-related OD patients and investigate potential underlying mechanisms.

Several studies have shown a high prevalence of olfactory dysfunction (OD) in COVID-19 patients, with meta-analyses reporting rates as high as 47.85%. Some studies suggest a female predominance. The use of smell diskettes testing for olfactory function has been established as a reliable and fast method to identify patients with normal olfaction versus those with hyposmia or anosmia. Previous research using MRI has demonstrated increased signal intensities and volumes in the olfactory bulb (OB) in COVID-19 patients experiencing anosmia, suggesting transient inflammation as a mechanism. Other studies have noted edema and swelling of the OB. Additionally, some research suggests that the virus's entry into the central nervous system through the olfactory system could lead to inflammatory changes in the olfactory cleft (OC), potentially causing mucosal edema and narrowing. Existing literature varies in its findings, with some studies showing OB atrophy in COVID-19 related anosmia, while others report mostly normal OB morphology and signal intensity. Previous studies have shown damage to the olfactory epithelium in patients with anosmia caused by viral upper respiratory tract infections, which has been confirmed through post-mortem studies of COVID-19 patients reporting OD, revealing focal atrophy of the olfactory epithelium, leukocytic infiltrations, and axonal damage.

This prospective study, conducted over one year at Mansoura University Hospitals in Egypt, enrolled 110 patients with post-COVID-19 OD (anosmia/hyposmia) and 50 COVID-negative controls with normal olfactory function. Participants underwent detailed history taking focusing on smell dysfunction and nasal complaints. Endoscopic nasal examination was performed, focusing on the OC, using a modified Lund-Kennedy score (OC-LK score) to assess the OC mucosa for discharge, polyps, edema, scarring, or crusting. Smell testing employed Briner's 8-smell diskette test. MRI of the olfactory pathway was performed on all participants using a 1.5 Tesla MR unit. Coronal 3D-FLAIR sequences were acquired. Image analysis was performed by blinded neuroradiologists, measuring OB dimensions and calculating volume using the Box-frame method. The condition of the OC (edema/opacity) and the presence of sinusitis were also assessed. Statistical analysis used the Statistical Package for Social Sciences (SPSS) software. Normality testing was performed using the Kolmogorov-Smirnov test. Qualitative data were described using number and percentages, categorical variable association was tested using the Chi-square test, and continuous variables were presented as mean ± SD or median (min-max). Group comparisons used the Student t-test for parametric data. Significance level was set at P ≤ .05.

A total of 160 participants were included (110 patients, 50 controls). There was no significant difference in age or gender distribution between groups. Patients' smell test scores ranged from 1 to 3, while controls scored 7 to 8. Taste alteration (ageusia/hypogeusia) was reported by 89.1% of patients. In 51.8% of patients, OD occurred without other nasal or general symptoms. Endoscopic assessment and MRI both showed significantly higher incidence of OC edema in patients compared to controls. MRI revealed sinusitis in 15.5% of patients and only 1 control subject. MRI showed significantly increased OB dimensions and volume in patients compared to controls, indicating edema and swelling. OB atrophy was observed in a small percentage (7.3%) of patients (unilateral in 2, bilateral in 6).

The findings of significantly larger olfactory bulb volumes in COVID-19-related olfactory dysfunction patients, coupled with a high incidence of olfactory cleft edema and the absence of sinonasal symptoms or significant sinusitis in most patients strongly supports the hypothesis that sensorineural loss is the primary mechanism. The likely pathway is viral spread and damage to the olfactory epithelium and central olfactory pathways. This is consistent with previous studies that have reported olfactory bulb edema, swelling and in some cases, atrophy in COVID-19 patients with olfactory dysfunction. The use of MRI has proven to be a valuable tool in identifying these abnormalities and further elucidating the underlying mechanisms. The study's results add to the existing body of evidence suggesting the role of viral spread along the olfactory pathway as the primary cause rather than solely nasal obstruction.

This study demonstrates significantly increased olfactory bulb volume in patients with COVID-19-related olfactory dysfunction, indicative of edema and swelling. The lack of associated sinonasal symptoms or radiologic evidence of sinusitis strongly suggests a sensorineural mechanism, likely involving viral spread and damage to the olfactory epithelium and pathways. Future research could focus on longitudinal studies to track the reversibility of these imaging findings and explore potential therapeutic interventions.

This study assessed clinical and imaging changes at a single time point. Long-term follow-up and repeated MRI were not performed. Previous studies suggest that COVID-19-related OD is often reversible, and imaging findings may be temporary. This limitation restricts the ability to definitively establish the long-term impact of the observed findings.