OBJECTIVE: This study aims to highlight the feasibility of an olfactory training program entirely monitored through online media in COVID-19 patients.
METHODS: Classic olfactory training was performed with a sample with olfactory loss due COVID-19 (n = 11). Participants were engaged on a weekly video call in order to improve adherence and collect information regarding the number of correct answers and the individuals\' perception of olfactory function. The olfactory status after training was compared to two groups, one composed of participants who contracted COVID-19 but did not report olfactory loss (n = 11) and a sample composed of healthy participants (n = 11).
RESULTS: The experimental group showed improvements throughout the training period (TDI score on week 0 was 20.3 (5.6) and 24.6 (4.3) for week 12, and on week 24 was 25.4 (6.2) (F = 5.115, df = 2, 20, p = 0.016), and post hoc tests showed that participants significantly improved their TDI score in W12 compared to W0 (SMD = 0.869, p = 0.041) and in W24 compared to W0 (SMD = 0.859, p = 0.041). The experimental group showed lower scores when compared with both groups, and the no OT COVID-19 group showed lower scores than the healthy control group, even though they did not report olfactory alterations.
CONCLUSIONS: Findings suggest that the strategies applied to improve adherence were successful since 100% of the sample completed the training adherence, offering a valuable framework for future olfactory training studies.

Introduction Persistent olfactory dysfunction was seen in many patients upon coronavirus disease 2019 (COVID-19) infection recovery. However, research on its management was very limited, especially among the Southeast Asian population. Objectives We aim to investigate the role of olfactory rehabilitation and topical corticosteroids among post-COVID-19 olfactory dysfunction patients in Malaysia, and at the same time to determine factors leading to olfactory recovery post-COVID-19 infection. Methods Adult Malaysians with persistent olfactory dysfunction one month post-COVID-19 recovery were recruited. Thirty-one patients were randomly assigned into three groups with 10 patients being given olfactory training (Group 1), another 10 being given mometasone furoate nasal spray/olfactory training (Group 2), and 11 patients being assigned to the control group (Group 3). All groups were followed up for an average duration of six months. Olfactory function was evaluated by Top International Biotech Smell Identification Test (TIBSIT) scores and Olfactory Disorder Questionnaire (eODQ) prior to randomization, at three and six months after recruitment. Results The baseline characteristics of patients were similar in all groups. Generally, patients of all three groups showed a statistically significant improvement in the TIBSIT scores after six months. The TIBSIT scores for Group 2 were statistically significantly higher than the control at three months but not at six months. As for Group 1, no statistically significant differences in TIBSIT scores at both three and six months were noted when compared to control. Statistically significant improvements were seen in the eODQ scores in all three groups. Conclusion No superiority of intervention for post-COVID-19 olfactory dysfunction was seen compared to control.

OBJECTIVE: The new corona virus infection, has a wide range of clinical manifestations. Fever and cough are the most common symptoms. The olfactory function may be also affected with COVID-19. In this randomized clinical trial, we wanted to evaluate the therapeutic effect of olfactory training with and without oral vitamin A for COVID-19-related olfactory dysfunction.
METHODS: Patients answered to the standard Persian version of anosmia reporting tool and performed the quick smell test before and after 12 weeks and at the end of the 12 months follow up. The patients were randomly allocated to three groups; Group A treatment with olfactory training, Group B treatment with oral vitamin A and olfactory training, and Group C as control group which only underwent nasal irrigation twice a day. Patients were treated for 3 months and followed up for 12 months.
RESULTS: Totally 90 patients were included in three groups. After interventions, 76.9% of patients in Group A, 86.7% of patients in Group B, and 26.7% of patients in Group C completely improved. The average intervention time was statistically significant in relationship with the final olfactory status of the patients in the 12 months follow-up. The olfactory training has significantly improved the smell alteration at the end of 3- and 12- months follow-up in A and B groups.
CONCLUSIONS: A three-months olfactory training is effective for improvement of COVID-19-related olfactory dysfunction. Adding daily oral vitamin A to olfactory training did not lead to better results in improving olfactory dysfunction.
METHODS: Step 2 (Level 2*): Randomized trial.

BACKGROUND: This longitudinal prospective study aims to investigate the potential of circulating calprotectin (cCLP) as a biomarker in persistent olfactory dysfunctions following COVID-19 infection.
METHODS: Thirty-six patients with persistent hyposmia or anosmia post COVID-19 were enrolled (HT0) and re-evaluated after three months of olfactory training (HT1). Two control groups included 18 subjects without olfactory defects post COVID-19 (CG1) and 18 healthy individuals (CG2). Nasal brushing of the olfactory cleft and blood collection were performed to assess circulating calprotectin levels.
RESULTS: Higher calprotectin levels were observed in serum and nasal supernatant of hyposmic patients (HT0) compared to control groups (CG1 and CG2). Post-olfactory training (HT1), olfactory function improved significantly, paralleled by decreased calprotectin levels in serum and nasal samples. Circulating calprotectin holds potential as a biomarker in persistent olfactory dysfunctions after COVID-19. The decrease in calprotectin levels post-olfactory training implies a role in monitoring and evaluating treatment responses.
CONCLUSIONS: These findings contribute to the growing literature on potential biomarkers in post-COVID-19 olfactory dysfunctions and underscore the importance of investigating novel biomarkers for personalized patient management. Nevertheless, further studies are needed to validate the application of calprotectin assay in nasal diseases and its correlation with nasal cytology.

UNASSIGNED: Olfactory disorders significantly affect individuals, diminishing their capacity to detect dangers, appreciate flavors, and engage socially. Despite their considerable impact on quality of life, these disorders often receive less attention compared to other sensory impairments. This review emphasizes the importance of olfactory function and explores both traditional and innovative diagnostic and therapeutic approaches.
UNASSIGNED: This review comprehensively covers the pathophysiology, diagnostic challenges, and treatment options for olfactory disorders. It delves into the nuances of different disorders, such as anosmia and parosmia, and discusses the array of diagnostic tools from traditional sniff tests to advanced imaging techniques. The review also evaluates therapeutic strategies, from pharmacological treatments to emerging therapies like electrical stimulation and regenerative medicine, highlighting recent advances in the field.
UNASSIGNED: Current insights suggest a growing recognition of the significance of olfactory disorders, driven by recent pandemics and advances in diagnostic and therapeutic technologies. Future perspectives indicate a promising direction toward more personalized medicine approaches and enhanced regenerative therapies. Continuous research and improved clinical awareness are critical for evolving the management strategies of olfactory impairments, potentially leading to better patient outcomes and quality of life enhancements.

UNASSIGNED: Olfactory training (OT) has emerged as a first-line therapeutic approach to the management of olfactory dysfunction. Conventional OT (COT) involves the systematic home-based exposure to four distinct odors. Previous research has demonstrated that immersive OT (IOT) involving full-body exposure to dozens of distinct odors could also improve overall olfactory function. This study compared IOT and COT in terms of efficacy.
UNASSIGNED: A total of 60 patients were enrolled and assigned to three groups. The IOT group (n = 25) underwent immersive exposure to 64 odors once daily in a specialized theater. COT participants (n = 17) sniffed four typical odors in a set of four jars twice daily at home. A control group (n = 18) underwent passive observation. Olfactory function was assessed before and after training.
UNASSIGNED: Significant improvements in composite threshold-discrimination-identification (TDI) scores were observed after training in both the IOT (mean difference = 2.5 ± 1.1. p = .030) and COT (mean difference = 4.2 ± 1.3, p = .002) groups. No changes were observed in the control group. A significantly higher proportion of patients in the COT group (41%) presented improvements of clinical importance (TDI ≥5.5) compared to the controls (p = .018). The improvements attained in the IOT group (20%) were less pronounced (p = .38).
UNASSIGNED: While IOT did not exhibit the same efficacy as COT in restoring olfactory function, it still demonstrated promising outcomes. Future efforts to advance olfactory recovery should focus on cross-modal integration.
UNASSIGNED: Level 3.

OBJECTIVE: Study the efficacy of olfactory training in smell recovery.
METHODS: An extensive search was performed through different databases in order to find articles analyzing the efficacy of olfactory training as a treatment for olfactory dysfunction. Methodological quality of primary studies within the final sample was assessed following PRISMA guidelines. Standardized mean differences in pre-post olfactory training groups, and also in experimental-control and pre-follow up if possible, were computed by Hedges\' g effect size statistic. Each effect size was weighted by its inverse variance.
RESULTS: Final sample was composed of 36 articles (45 pre-post effect sizes). Contrasts were performed separately for odor identification, odor discrimination, odor threshold and general olfactory function. Moderate to large and heterogeneous effect was obtained for olfactory function (g = 0.755, k = 45, SE = 0.093, CI 95% = [0.572, 0.937]), different moderators had a significant effects, such as, training duration, age and anosmia diagnosis.
CONCLUSIONS: Olfactory training was found to have a positive and significant effect on rehabilitating the olfactory function.

Systematic exposure to odours (olfactory training, OT) is a method of smell loss treatment. Due to olfactory system projections to prefrontal brain areas, OT has been hypothesized to enhance cognitive functions, but its effects have been studied predominantly in adults. This study tested OT effects on working memory (WM), i.e., the ability to store and manipulate information for a short time, in healthy children aged 6-9 years. We expected OT to improve olfactory WM and establish cross-modal transfer to visual and auditory WM. Participants performed 12 weeks of bi-daily OT with either 4 odours (lemon, eucalyptus, rose, cloves; OT group) or odourless propylene glycol (placebo group). Pre- and post-training, participants\' WM was measured utilizing odours (olfactory WM) or pictures (visual WM) and a word-span task (auditory WM). 84 children (40 girls) completed the study. The analyses revealed no changes in the WM performance following OT. The olfactory WM task was the most difficult for children, highlighting the need to include olfactory-related tasks in educational programmes to improve children\'s odour knowledge and memory, just as they learn about sounds and pictures. Further neuroimaging research is needed to fully understand the impact of OT on cognitive functions in children.

Olfactory dysfunction (OD) is not uncommon following viral infection. Herein, we explore the interplay of host genetics with viral correlates in coronavirus disease 2019 (COVID-19)- and long COVID-related OD, and its diagnosis and treatment that remain challenging. Two genes associated with olfaction, UGT2A1 and UGT2A2, appear to be involved in COVID-19-related anosmia, a hallmark symptom of acute infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), particularly in the early stages of the pandemic. SARS-CoV-2 infects olfactory support cells, sustentacular and Bowman gland cells, that surround olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) where the initial step of odor detection takes place. Anosmia primarily arises from the infection of support cells of the OE, followed by the deciliation and disruption of OE integrity, typically without OSN infection. Through the projected axons of OSNs, the virus could theoretically reach the olfactory bulb and brain, but current evidence points against this route. Intriguingly, SARS-CoV-2 infection of support cells leads to profound alterations in the nuclear architecture of OSNs, leading to the downregulation of odorant receptor-related genes, e.g., of Adcy3. Viral factors associated with the development of OD include spike protein aminoacidic changes, e.g., D614G, the first substitution that was selected early during SARS-CoV-2 evolution. More recent variants of the Omicron family are less likely to cause OD compared to Delta or Alpha, although OD has been associated with a milder disease course. OD is one of the most prevalent post-acute neurologic symptoms of SARS-CoV-2 infection. The tens of millions of people worldwide who have lingering problems with OD wait eagerly for effective new treatments that will restore their sense of smell which adds value to their quality of life.

OBJECTIVE: Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment.
METHODS: After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin\' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia.
RESULTS: The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated.
CONCLUSIONS: umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit.