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Background: COVID-19 has been associated with olfactory dysfunction in many infected patients. The rise of calcium levels in the nasal secretions plays an essential role in the olfaction process with a desensitization effect on the olfactory receptor neurons and a negative impact on the olfaction transmission. Ethylene diamine tetra acetic acid (EDTA) is a chelating agent that can bind free calcium in the nasal secretions, thereby reducing the adverse effects of calcium on olfactory function., Objectives: The objective of this work is to demonstrate the effect of intranasal EDTA on improving olfactory dysfunction following COVID-19., Methods: Fifty patients with a history of COVID-19 and olfactory dysfunction that persisted for more than 6 months were enrolled in the current prospective randomized clinical trial. Participants were randomized into 2 equal groups. Twenty-five patients were treated with olfactory training only, while the remaining 25 patients received treatment with olfactory training and a topical nasal spray of ethylene diamine tetra acetic acid. The olfactory function was assessed before treatment and 3 months later using the Sniffin' Sticks test. Additionally, the determination of calcium level in the nasal secretions was performed using an ion-selective electrode before treatment and 3 months later., Results: Eighty-eight percent of the patients treated with olfactory training in addition to EDTA exhibited clinical improvement, while 60% showed improvement in patients treated with olfactory training only. Furthermore, a significant decrease in the measured calcium level in the nasal secretions was demonstrated after the use of ethylene diamine tetra compared to patients treated with olfactory training only., Conclusion: Ethylene diamine tetra acetic acid may be associated with an improvement of the olfactory function post-COVID-19., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To evaluate the efficacy of omega-3 fatty acid (O3FA) supplementation in the treatment of COVID-related olfactory dysfunction (OD)., Methods: Patients with laboratory-confirmed or clinically-suspected COVID-19 infection and new-onset OD from August 2020 to November 2021 were prospectively recruited. Patients with quantitative OD, defined as a brief smell identification test (BSIT) score of 9 or less, were eligible for study inclusion. The experimental group received 2 g of O3FA supplementation, while the control group received an identical placebo to be taken daily for 6 weeks. The primary outcome was a change in BSIT score between the initial and 6-week follow-up tests., Results: One hundred and seventeen patients were included in the analysis, including 57 patients in the O3FA group and 60 in the placebo group. O3FA group patients demonstrated a mean BSIT improvement of 1.12 ± 1.99 compared to 0.68 ± 1.86 in the placebo group ( p  = 0.221). Seventy-seven patients, 42 within the O3FA group and 35 in the placebo group, completed a follow-up BSIT survey at an average of 717.8 days from study onset. At long-term follow-up, there was an average BSIT score improvement of 1.72 within the O3FA group compared to 1.76 within the placebo group ( p  = 0.948)., Conclusion: Among patients with persistent COVID-related OD, our study showed no clear evidence of relative short-term or long-term olfactory recovery among patients receiving high doses of O3FA supplementation.

Background: COVID-19 has been associated with temporary olfactory dysfunction in many infected patients. Calcium plays a great role in the olfaction process with negative feedback for the olfaction transmission. Many reports demonstrated calcium elevation in the nasal secretions with a negative effect on olfaction. Sodium gluconate is a water-soluble salt with a chemical structure that lends to act as a highly efficient chelating agent. It can bind the elevated calcium in the nasal secretions reducing the adverse effects on olfactory function., Objective: To evaluate the impact of intranasal sodium gluconate on decreasing the rise of nasal calcium and improving the sense of smell in patients with olfactory dysfunction post-COVID-19 infection., Methods: Fifty patients with a history of confirmed COVID-19 suffering from olfactory dysfunction persisted more than 90 days after severe acute respiratory syndrome-coronavirus-2 negative testing were included in a prospective randomized blinded controlled clinical trial. Patients were divided into 2 equal groups, receiving either 0.9% sodium chloride or 1% sodium gluconate. Olfactory function was assessed before treatment and 1 month later using the Sniffin' Sticks test. Quantitative analysis of the nasal calcium concentration was performed before treatment and 1 month later using a laboratory-designed screen-printed ion-selective electrode., Results: After using sodium gluconate, the measured olfactory scores indicated a clinical improvement from anosmia to hyposmia compared to the nonimprovement sodium chloride receiving group. Also, a remarked decrease in the calcium nasal concentration was observed after using sodium gluconate compared to sodium chloride., Conclusion: Based on the proposed results, sodium gluconate may associate with an improvement of the olfactory dysfunction post-COVID-19 infection.

Objective: Steroid therapy and olfactory training are common treatments for olfactory loss. Systemic steroid treatment is the most effective approach for treating sinonasal olfactory loss. Olfactory training is typically effective for treating sensorineural olfactory loss. However, the differences in mechanisms of steroid therapy and olfactory training for olfactory dysfunction are unclear. The aim of this study was thus to evaluate the differences in mechanisms of olfactory training and steroid therapy., Subjects and Methods: Mice in each group were administered 3-methylindole at a dose of 300 mg/kg. Olfactory function was evaluated with a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis. Subsequently, data analysis, gene ontology and pathway analysis, quantitative real-time polymerase chain reaction of mRNA, and western blot analysis were conducted., Results: Mice were divided into four groups according to treatment. Control, anosmia, training, and steroid groups resumed food-finding. MMP27, CCL22 and IL18rap mRNA expression were significantly increased in the training group compared to that in the steroid group. IL1R2 mRNA expression was significantly higher in the olfactory neuroepithelium of steroid-treated mice than in that of the training group mice., Conclusions: Steroid therapy improved olfactory function via anti-inflammatory effects, unlike olfactory training which involved cell regeneration and tissue remodeling. Protein and gene analyses revealed that steroid therapy and olfactory training are underpinned by distinct mechanisms. Selection of the most appropriate treatment will be dependent on the cause of olfactory loss.

Background: Despite the importance of olfactory function, no effective medications have been identified to treat olfactory disorders. This study was performed to evaluate the functional recovery of olfaction damaged by 3-methylindole (3MI) in a mouse model with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins)., Methods: In a randomized placebo-controlled trial, 24 healthy female BALB/c mice (aged 9-10 weeks and weighing 18-20 g each) were randomly allocated to statin-treated or control groups. Olfactory loss was induced by i.p. injections of 3MI. Atorvastatin (10 mg/kg) or normal saline was then administered per os with a gastric tube for 3 weeks. The effects of treatment were evaluated by food-finding tests and Western blot analysis., Results: Both groups showed complete losses of olfactory function 1 week after 3MI injection. Three weeks after 3MI injection, 9 of the 12 mice in the statin-treated group (75%) passed a food-finding test, in which they were able to find the food within 3 minutes, at least two times out of three trials. However, only two mice in the control group (16.6%) passed the food-finding test, and this difference was statistically significant (p = 0.004; chi-square test). The expression level of the olfactory marker protein was also elevated in the statin-treated group (p = 0.030; Wilcoxon rank sum test)., Conclusion: Statins are associated with recovery of olfaction after 3MI injection in a mouse model.

Background: Olfactory bulb (OB) volume has been shown to be an indicator of olfactory function. However, few studies have been done in Asia to investigate the influence of different disorders on OB volume., Methods: Data from patients with posttraumatic anosmia were collected in our department. Their olfactory thresholds were assessed by the phenyl ethyl alcohol threshold test. They were treated with a course of high-dose steroid, and followed up for at least 3 months without any olfactory improvement. Magnetic resonance imaging was subsequently used to measure patients' OB volumes. Subjects who self-reported their olfactory function was normal were also included in the control group for comparison., Results: Fifty-four patients with posttraumatic anosmia and 30 subjects who self-reported their olfactory function was normal were enrolled in this study. The mean right OB volume was 45.2 mm3, and the mean left OB volume was 46.3 mm3 in patients with posttraumatic anosmia. The mean right OB volume was 59.7 mm3, and the mean left OB volume was 66.0 mm3 in control subjects. The OB volumes were significantly lower in patients with posttraumatic anosmia., Conclusion: OB volumes were significantly lower in Taiwanese patients with posttraumatic anosmia.