Intranasal Corticosteroid Treatment on Recovery of Long-Term Olfactory Dysfunction Due to COVID-19.

BACKGROUND AND AIMS: Olfactory dysfunction is a recognized manifestation in patients infected with Coronavirus Disease 2019 (COVID-19). This investigation aimed to assess the effect of mometasone furoate intranasal spray on the improvement of smell dysfunction in post-COVID-19 patients. MATERIALS AND METHODS: This randomized placebo-controlled trial included 80 non-hospitalized adult patients who had persistent anosmia or severe microsmia for more than 4 weeks due to COVID-19 infection. The participants were randomly allocated to the intervention or placebo group to receive mometasone furoate nasal spray or sodium chloride intranasal spray during 4 weeks of follow-up, respectively. The patients' olfactory dysfunction was assessed in terms of visual analog scale (VAS), and smell test score according to the modified version of the University of Pennsylvania smell identification test for the Iranian population. RESULTS: A total of 70 participants completed the follow-up period and were analyzed in this study. By comparing the olfactory scores including smell test and VAS scores, no significant differences were found between case and control groups at baseline, 2, and 4 weeks intervals. However, the change of both olfactory scores at pre to post-treatment intervals and 2-4 weeks was significantly higher in the mometasone group relative to the placebo group. At post-treatment, the frequency of anosmia was 22.9% reduced in the case group compared to the control group. CONCLUSION: Overall, there was no significant difference in olfactory dysfunction between the two groups during follow-up. However, based on the significant between-group difference in terms of olfactory scores changes, it seems that the nasal corticosteroids may be a positive effect on the recovery process of patients who received more than 2 weeks. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:2209-2216, 2022.

COCOS trial: COrticosteroids for COVID-19-induced loss of Smell-protocol for a single-centred, double-blind, randomised, placebo-controlled trial.

INTRODUCTION: Hyposmia and anosmia are common in COVID-19. Most patients regain normal smell within 4 weeks, but severe loss of smell persists roughly in 20% after 2 months and may last up to a year or longer. These persistent smell disorders greatly influence daily life. It is hypothesised that COVID-19 induces inflammation around the olfactory nerve and in the olfactory pathway, leading to smell disorders. Corticosteroids might reduce this local inflammatory response and improve smell. METHODS AND ANALYSIS: We will conduct a single-centre, randomised, placebo-controlled trial to determine the efficacy of a short high-dose treatment of oral prednisolone for persistent loss of smell after COVID-19 in the early phase. We will include 116 patients with persistent (>4 weeks) loss of smell within 12 weeks of COVID-19 diagnosis, based on a positive PCR/antigen test. One group receives 40 mg of prednisolone for 10 days and the other group receives matching placebo treatment. In addition, all patients will perform smell training for 12 weeks. The primary outcome is objective olfactory function measured by means of sniffin' sticks test. Secondary outcomes are objective gustatory function by means of taste strips test and subjective taste and smell ability, trigeminal sensations, quality of life and nasal symptoms, measured by three questionnaires. These outcomes will be measured at inclusion before treatment and 12 weeks later. ETHICS AND DISSEMINATION: The Institutional Review Board of the University Medical Center Utrecht approved the research protocol (21-635/G-D, October 2021). The trial results will be shared in peer-reviewed medical journals and scientific conferences. TRIAL REGISTRATION NUMBER: NL9635. EUCTR2021-004021-71-NL.

Efficacy of topical steroids for the treatment of olfactory disorders caused by COVID-19: A systematic review and meta-analysis.

OBJECTIVES: The aim of this study was to assess the effect of topical steroids on acute-onset olfactory dysfunction in patients infected with COVID-19. DESIGN AND SETTING: Systematic review and meta-analysis of cohort studies. PARTICIPANTS: Patients infected with COVID-19. MAIN OUTCOME MEASURES: PubMed, Embase, the Web of Science, SCOPUS, Cochrane database and Google Scholar were searched for articles up to September 2021. We analysed studies comparing the improvement of olfactory dysfunction between topical steroid treatment and control groups (placebo or no treatment). In addition, we performed a subgroup analysis by study type. RESULTS: The improvement of olfactory score at 2 (standardised mean difference [SMD] = 0.7272, 95% confidence interval = [0.3851, 1.0692], p < .0001, I2  = 62.1%) and 4 weeks post-treatment (SMD = 1.0440 [0.6777, 1.4102], p < .0001, I2  = 61.2%) was statistically greater in the treatment than control group. However, there was no significant difference (odds ratio [OR] = 1.4345 [0.9525, 2.1604], p = .0842, I2  = 45.4%) in the incidence of fully recovery from anosmia/hyposmia between the treatment and control groups. In subgroup analysis, there were no significant differences in the improvement of olfactory score at 4 weeks post-treatment (OR = 0.6177 [0.1309, 1.1045] vs. 0.1720 [0.8002, 1.5438], p = .0761) or the incidence of full recovery from anosmia/hyposmia (OR = 1.8478 [0.6092, 5.6053] vs. 1.3784 [0.8872, 2.1414], p = .8038) between randomised and non-randomised controlled trials. CONCLUSIONS: Although this meta-analysis found that topical steroids improved the acute-onset olfactory dysfunction caused by COVID-19, there was no difference in the rate of full olfactory recovery between treated and control patients.

Possible Use of Phytochemicals for Recovery from COVID-19-Induced Anosmia and Ageusia.

The year 2020 became the year of the outbreak of coronavirus, SARS-CoV-2, which escalated into a worldwide pandemic and continued into 2021. One of the unique symptoms of the SARS-CoV-2 disease, COVID-19, is the loss of chemical senses, i.e., smell and taste. Smell training is one of the methods used in facilitating recovery of the olfactory sense, and it uses essential oils of lemon, rose, clove, and eucalyptus. These essential oils were not selected based on their chemical constituents. Although scientific studies have shown that they improve recovery, there may be better combinations for facilitating recovery. Many phytochemicals have bioactive properties with anti-inflammatory and anti-viral effects. In this review, we describe the chemical compounds with anti- inflammatory and anti-viral effects, and we list the plants that contain these chemical compounds. We expand the review from terpenes to the less volatile flavonoids in order to propose a combination of essential oils and diets that can be used to develop a new taste training method, as there has been no taste training so far. Finally, we discuss the possible use of these in clinical settings.

Mometasone furoate nasal spray in the treatment of patients with COVID-19 olfactory dysfunction: A randomized, double blind clinical trial.

The aim of this study was to evaluate the usage of mometasone furoate nasal spray in the recovery of patients with severe microsmia or anosmia induced by COVID-19. This was a prospective clinical trial on non-hospitalized adult patients with COVID-19 (>18 years) who had severe microsmia or anosmia within two weeks. The subjects were randomly assigned to the mometasone furoate group (100 mcg twice daily) or sodium chloride group (0.9%); both groups also received olfactory training for 4 weeks. The primary outcome was the improvement of the olfactory score at the end of the study. Visual analog scale (VAS) and the University of Pennsylvania Smell Identification Test (UPSIT) were used to assess primary outcome. A total of 80 patients were recruited, 77 of them completed the study and were analyzed. There was no statistically significant difference in terms of demographics and baseline clinical characteristics. The olfactory scores (based on VAS) at weekly intervals showed a significant difference between the two groups (P:0.318, <0.001, <0.001, <0.001, respectively). The analyses also showed significant within-group differences from baseline. Nevertheless, the changes were not significant between the two groups (P: 0.444, 0.402, 0.267, 0.329). There was no significant difference between the two groups in terms of the UPSIT results (p > 0.239). However, a significant between-group difference was noted in the severity of loss of smell (P < 0.001). Compared to olfactory training, mometasone furoate nasal spray combination with olfactory training showed a higher improvement in severe chronic anosmia by COVID-19.

Effect of nasal corticosteroid in the treatment of anosmia due to COVID-19: A randomised double-blind placebo-controlled study.

OBJECTIVES: Anosmia is a common debilitating symptom of the novel coronavirus disease 2019 (COVID-19). Currently, there is no satisfactory treatment of anosmia. Therefore, this study was conducted to evaluate the therapeutic effect of nasal betamethasone drops in the recovery of olfaction in COVID-19-associated anosmia. METHODS: The study was designed as a randomised, double-blind, placebo-controlled clinical trial. In total, 276 PCR-confirmed COVID-19 patients who were presented to the outpatient clinic with anosmia were enrolled in the study. In the betamethasone group, 138 participants received nasal drops of betamethasone 3 times daily until recovery for a maximum of one month. Similar dose of 9% NaCl drops was administered to 138 participants in the placebo group. RESULTS: The median age of participants was 29 years (IQR 23-37). Among them, 198 (71.7%) were females. Ageusia was co-presented with anosmia in 234 (84.8%) of participants. In this study, 83% of participants had recovered from anosmia within 30 days, with a median recovery time of 13 days (IQR 8-18). Compared to placebo, nasal application of betamethasone drops has no significant effect on the recovery time of anosmia (hazard ratio 0.88; 95% CI 0.68-1.14; P = 0.31). CONCLUSION: The use of nasal betamethasone to facilitate the recovery time of acute anosmia is not advised. In addition, age, smoking status, the duration of anosmia at presentation, and the co-presentation of ageusia with anosmia are important determinant covariates for the recovery time of anosmia. Further clinical trials, which take these covariates into account, will need to be undertaken. The trail has been registered at ClinicalTrails.gov, NCT04569825.

The outcome of fluticasone nasal spray on anosmia and triamcinolone oral paste in dysgeusia in COVID-19 patients.

BACKGROUND: To study the outcome of fluticasone nasal sprays in smell disorders and triamcinolone paste in taste dysfunction in a population of laboratory-confirmed SARS-CoV-2 patients as the test group. The control group will not be given any intervention and only monitoring of these symptoms will be done to compare the recovery time. METHODS: This prospective interventional study was conducted from June to Nov 2020 at, Datta Meghe University during the COVID-19 outbreak. The 120 enrolled patients were tested at days 1 and 5 after proven infection by RT-PCR test. RESULT: The mean age for all cases is 50.88 ± 15.93 years, whereas for the controls mean age is 51.2 ± 14.89. 2. Among cases 45 (75%) were males and 15 (25%) were females, among controls 43 (71.66%) were males and 17 (28.33%) were females. Among the case group, after the use of fluticasone spray in the nose and triamcinolone paste in the mouth there was a statistically significant improvement in recognizing all the odours and taste on day 5 compared to day 1. On comparing the smell and taste of cases and control group, either there is no improvement or worsening in smell or taste on day 5 in the control group. CONCLUSION: The use of fluticasone nasal spray and triamcinolone paste had immensely influenced the basic senses such as smell and taste. Our study showed that olfactory and taste function significantly improved in patients with COVID-19. For all anosmia and dysgeusia cases who received fluticasone nasal spray and triamcinolone medications the recovery of smell senses and the taste was within a week.

Corticosteroid nasal spray for recovery of smell sensation in COVID-19 patients: A randomized controlled trial.

OBJECTIVES: To evaluate the role of the topical corticosteroid, mometasone furoate, nasal spray in the treatment of post COVID-19 anosmia. METHODS: A prospective, randomized, controlled trial was conducted among patients with post COVID-19 anosmia. One hundred patients were randomly assigned to two groups; group I included 50 patients received mometasone furoate nasal spray in an appropriate dose of 2 puff (100 µg) once daily in each nostril for 3 weeks with olfactory training, group II included 50 patients were advised to keep on olfactory training only. The assessment of smell was done using (Visual Analog Scale from 0 to 10). All patients were initially evaluated after their recovery from COVID-19 and followed up for 3 weeks. The smell scores were recorded weekly and the duration of smell loss was recorded from the onset of anosmia till the full recovery. RESULTS: In both groups, the smell scores significantly improved by the end of the third week (P < 0.001). By comparing smell scores between both groups after 1 week, 2 weeks, and 3 weeks of treatment, there were no statistically significant differences between both groups. In group I, (62%) of patients completely recovered their sense of smell after 3 weeks of treatment, compared to (52%) of patients in group II (P = 0.31). CONCLUSION: The results suggested that using mometasone furoate nasal spray as a topical corticosteroid in the treatment of post COVID-19 anosmia offers no superiority benefits over the olfactory training, regarding smell scores, duration of anosmia, and recovery rates. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT04484493.

Olfactory epithelium histopathological findings in long-term coronavirus disease 2019 related anosmia.

BACKGROUND: Olfactory dysfunction represents one of the most frequent symptoms of coronavirus disease 2019, affecting about 70 per cent of patients. However, the pathogenesis of the olfactory dysfunction in coronavirus disease 2019 has not yet been elucidated. CASE REPORT: This report presents the radiological and histopathological findings of a patient who presented with anosmia persisting for more than three months after infection with severe acute respiratory syndrome coronavirus-2. CONCLUSION: The biopsy demonstrated significant disruption of the olfactory epithelium. This shifts the focus away from invasion of the olfactory bulb and encourages further studies of treatments targeted at the surface epithelium.