Effects of Frequency-Controlled Ear Acupuncture on COVID-19- related Refractory Olfactory Dysfunction: a Randomized Clinical Trial.

Background: Olfactory dysfunction is a common COVID-19 symptom, posing treatment challenges. Objectives: We aimed to investigate the efficacy of frequency-controlled ear acupuncture in treating COVID-19-related olfactory dysfunction. Methods: A randomized, participant-blind clinical trial occurred at the Rasoul Akram Hospital (IRCT20210311050671N1). Forty patients were recruited, and 20 patients were randomly assigned to either the experimental or control group. The primary outcome was the improvement in patients' quality of smell. The olfactory dysfunction was confirmed using the Smell Identification Test. The intervention group received two sessions of acupuncture treatment according to auricular frequency treatment, with a one-week interval, while the control group received an equal number of switched-off laser sessions. Both groups were instructed to use nasal betamethasone drops. The patients were asked to rank their ability to smell before and after each intervention on a 10-point visual analog scale. Secondary outcomes were related side effects. Results: Covariance analysis revealed a significant difference in adjusted scores between the groups (F [37, 1] = 37.463; p = 0.000, Eta2 = 0.503). The smell quality improved from 2.80 ± 1.76 to 5.22 ± 3.40 after treatment in the intervention group (p = 0.007), while the control group showed no significant change (p = 0.184). Three patients reported short and transient side effects, such as nausea, headache, and dizziness, in the first hours after the intervention. Conclusion: Frequency-controlled ear acupuncture is an effective option for treating COVID-19-related olfactory dysfunction. The study highlights the potential of alternative therapies in the treatment of this condition, and further research is warranted to investigate its long-term effects.

Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review.

Olfactory training (OT), or smell training,consists of repeated exposure to odorants over time with the intended neuroplastic effect of improving or remediating olfactory functioning. Declines in olfaction parallel declines in cognition in various pathological conditions and aging. Research suggests a dynamic neural connection exists between olfaction and cognition. Thus, if OT can improve olfaction, could OT also improve cognition and support brain function? To answer this question, we conducted a systematic review of the literature to determine whether there is evidence that OT translates to improved cognition or altered brain morphology and connectivity that supports cognition. Across three databases (MEDLINE, Scopus, & Embase), 18 articles were identified in this systematic review. Overall, the reviewed studies provided emerging evidence that OT is associated with improved global cognition, and in particular, verbal fluency and verbal learning/memory. OT is also associated with increases in the volume/size of olfactory-related brain regions, including the olfactory bulb and hippocampus, and altered functional connectivity. Interestingly, these positive effects were not limited to patients with smell loss (i.e., hyposmia & anosmia) but normosmic (i.e., normal ability to smell) participants benefitted as well. Implications for practice and research are provided.

Olfactory dysfunction and training in children with COVID-19 infection: A prospective study Post-COVID pediatric olfactory training.

OBJECTIVE: Postviral olfactory dysfunction (OD) including corona 2019 viral disease (COVID-19) OD occurs in both adults and children. Despite limited reports of efficacy in treating adult postviral including COVID-19 OD with olfactory training (OT), its effects on children in general, and post-COVID-19 in specific, is unknown. The study aimed at evaluating the effects of OT in a COVID-19 OD pediatric cohort. METHODS: A single-arm prospective study of pediatric COVID-19 OD subjects confirmed by the University of Pennsylvania Smell Identification Test (UPSIT), was conducted. All subjects underwent OT by sniffing 4 odorants (lavender, orange, peppermint, and eucalyptus) for 1 min twice a day for 3 months. Subjects underwent an odorant identification test (OIT) of the 4 odorants each visit. A repeat UPSIT was administered at the 4th visit. RESULTS: The study enrolled a total of 37 subjects [11 males/26 females with mean age/standard deviation (std) of 15.6(2.1) years]. The time interval between COVID-19 and entry was 5.3(2.4) months. The mean pre/post study UPSIT score improvement was 2.3(4.7), p = .09. OIT scores between entry and 3 subsequent visits showed a mean improvement of 1.8(1.5), 1.8(1.9) and 2.3(1.9) odorants, respectively, with P < .001 for all 3 comparisons. CONCLUSIONS: OT subjects were predominantly female teens with substantial OD lasting greater than 5 months. OT did not affect OD as measured by UPSIT but OIT scores improved during OT. We postulate that OT likely has a role in pediatric post-COVID OD recovery, but UPSIT likely is too rigid to detect disparate odorant improvement.

Olfactory training in normosmic individuals: a randomised controlled trial.

BACKGROUND: Even if olfactory training (OT) is a well-established treatment for individuals with olfactory dysfunction, the effect on individuals with normosmia remains uncertain. In this randomised controlled trial, we explore how OT with different exposure lengths affect olfactory function in individuals with normosmia. METHODOLOGY: Two hundred normosmic individuals were randomly assigned to one of two intervention groups performing OT with different exposure lengths or to a control group. The OT groups did OT twice daily for three months, g four different odours (eucalyptus, lavender, mint, and lemon) for 10 seconds per bottle during either a total of 40 seconds (standard OT) or 4 minutes (extended OT), while the control group did not perform any OT. Olfactory function was assessed using a 48-item Sniffin Sticks test at baseline, after the intervention, and after one year. RESULTS: We found no significant effect of OT in either of the intervention groups on any aspect of olfaction after intervention or at follow-up. There was no association between sex, age, allergic rhinitis, education or olfactory scores at baseline, and changes in olfactory function after OT. The extended OT group performed significantly fewer training sessions compared to those in the standard OT group. CONCLUSIONS: OT had a limited effect on olfactory function in individuals with normosmia. Further, the superiority of a more extended OT is not supported by this study, and shorter training sessions seem to improve compliance with OT.

Effectiveness of Platelet-Rich Plasma for COVID-19-Related Olfactory Dysfunction: A Controlled Study.

OBJECTIVE: To investigate the effectiveness of platelet-rich plasma (PRP) injection into the olfactory clefts of coronavirus disease 2019 (COVID-19) patients with persistent olfactory dysfunction (OD). STUDY DESIGN: Controlled study. SETTING: Multicenter study. METHODS: From March 2022 to November 2022, COVID-19 patients with persistent OD were recruited from three European hospitals to undergo PRP injections into the olfactory clefts. Olfactory function was evaluated at baseline and 10 weeks postinjection with the Olfactory Disorder Questionnaire (ODQ) and threshold, discrimination, and identification (TDI) test. Data were compared with a control group of untreated patients. RESULTS: Eighty-one patients who underwent PRP injection and 78 controls were included. Sixty-five PRP patients (80.3%) experienced subjective smell improvement after a mean duration of 3.4 ± 1.9 weeks. The parosmia, life quality statement, and ODQ sub- and total scores significantly decreased from pre- to 10-week postinjection in the PRP group. The TDI sub- and total scores significantly increased 10 weeks postinjection. In controls, the ODQ score did not change over time, while the discrimination, identification, and total TDI scores significantly increase after 10 weeks of follow-up. The 10-week TDI and ODQ scores were significantly better in the PRP group compared with the controls. CONCLUSION: Patients who underwent PRP injection reported better 10-week subjective and objective smell outcomes than controls. Future randomized-controlled studies using saline injection into the olfactory cleft of controls are needed to determine the superiority of PRP over placebo.

Stellate Ganglion Block for the Treatment of COVID-19-Induced Olfactory Dysfunction: A Prospective Pilot Study.

OBJECTIVE: The objective of this study was to explore the safety and feasibility of stellate ganglion blocks (SGBs) to treat persistent COVID-19-induced olfactory dysfunction (OD). Secondarily, the goal was to determine effect sizes to plan a future randomized clinical trial. STUDY DESIGN: Prospective case series. SETTING: Quaternary Care Academic Medical Center. METHODS: In this single-arm pilot trial, adult participants with a COVID-19 diagnosis ≥ 12 months prior to enrollment with OD underwent bilateral SGBs. Subjects were followed for 1 month after completion of SGB. The primary outcome measure was the change in the Clinical Global Impression-Improvement Scale for smell loss. Secondary outcome measures included changes in the University of Pennsylvania Smell Identification Test (UPSIT) and Olfactory Dysfunction Outcomes Rating (ODOR). RESULTS: Twenty participants were enrolled with a mean (SD) age of 46 (11) years and a mean (SD) duration of OD of 21 (5) months. At 1 month, 10 (50%) participants experienced at least slight subjective improvement in their OD, 11 (55%) attained a clinically meaningful improvement in smell identification using the UPSIT, and 7 (35%) achieved a clinically meaningful improvement in olfactory-specific quality of life (QoL) measured by the ODOR. The median difference between UPSIT scores at baseline and 1 month was 6 (95% confidence interval: 3-11), exceeding the minimal clinically important difference of 4. There were no serious adverse events. CONCLUSION: Sequential SGBs for COVID-19-associated OD were safe and associated with modest improvements in subjective olfaction, odor identification, and olfactory-specific QoL. A placebo-controlled trial is warranted to determine the efficacy of SGBs for COVID-19-associated OD.

Hyperbaric oxygen therapy for treatment of COVID-19-related parosmia: a case report.

Parosmia is a qualitative olfactory dysfunction characterized by distortion of odor perception. Traditional treatments for parosmia include olfactory training and steroids. Some patients infected with COVID-19 have developed chronic parosmia as a result of their infection. Here, we present the case of a patient who developed parosmia after a COVID-19 infection that was not improved by traditional treatments but found significant improvement after hyperbaric oxygen therapy[A1].

Effectiveness of platelet-rich plasma on post-COVID chronic olfactory dysfunction.

OBJECTIVE: The aim of this study was to investigate the efficacy of platelet-rich plasma injection on the olfactory cleft of patients with post-COVID olfactory dysfunction lasting over 1 year, who were unresponsive to common treatments. METHODS: Patients over 18 years of age with post-COVID olfactory dysfunction over 1 year whose complaints did not improve with intranasal steroids and D-panthenol/vitamin A combination nasal sprays with olfactory rehabilitation training for 1 month were prospectively collected and randomized into two groups: intranasal platelet-rich plasma group and control group. At the end of 1 month, Connecticut Chemosensory Clinical Research Center olfaction test scores of smell detection threshold and smell identification test were compared accordingly. RESULTS: A total of 25 patients were randomized into platelet-rich plasma (n=12) and control (n=13) groups. In the platelet-rich plasma group, the mean smell detection threshold score increased from 5.63 (SD 0.68) to 6.46 (SD 0.45), and the mean smell identification test score increased from 11.42 (SD 1.17) to 15.17 (SD 0.39). In the control group, the mean smell detection threshold score changed from 5.69 (SD 0.66) to 5.77 (SD 0.70), and the mean smell identification test score changed from 11.20 (SD 1.12) to 11.85 (SD 1.57). Post-hoc analysis revealed that similar mean smell detection threshold (mean difference 0.07; p=0.994) and smell identification test (mean difference -0.50; p=0.703) scores were transformed into a significant difference between groups (smell detection threshold mean difference 0.69; p=0.037; smell identification test mean difference 3.32; p<0.001). CONCLUSION: At the end of the first month, there was a significant improvement in olfactory threshold values in the platelet-rich plasma group compared to the control group. No side effect or adverse event related to platelet-rich plasma injection was observed.

[Diagnostics and treatment of olfactory disorders]. / Reukstoornissen in de klinische praktijk.

Olfactory disorders are common and have consequences for the quality of life of patients. The main causes are post viral upper respiratory tract infections, head trauma and sinonasal disease. However, there are many more less frequent causes which we illustrate by showing three different rare cases. A distinguishment between qualitative and quantitative olfactory disorders is made which is mainly based on the patient's history and olfactory testing. It is important to diagnose the cause of an olfactory disorder because treatment options are dependent on it and it can be a symptom of a progressive disease. Olfactory training is a proven treatment for many perceptive olfactory disorders and is easily performed by most patients.

Mechanism and treatment of olfactory dysfunction caused by coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since the start of the pandemic, olfactory dysfunction (OD) has been reported as a common symptom of COVID-19. In some asymptomatic carriers, OD is often the first and even the only symptom. At the same time, persistent OD is also a long-term sequela seen after COVID-19 that can have a serious impact on the quality of life of patients. However, the pathogenesis of post-COVID-19 OD is still unclear, and there is no specific treatment for its patients. The aim of this paper was to review the research on OD caused by SARS-CoV-2 infection and to summarize the mechanism of action, the pathogenesis, and current treatments.

[Persistent olfactory impairment after COVID-19-recommendations of the Working Group on Olfactology and Gustology of the German Society of Oto-rhino-laryngology, Head and Neck Surgery]. / Persistierende Riechminderung nach COVID-19 ­ Empfehlungen der Arbeitsgemeinschaft Olfaktologie und Gustologie der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

This article does not intend to comprehensively review the existing literature on coronavirus disease 2019 (COVID-19)-associated smell disorders, but aims to summarize scientific evidence for otorhinolaryngological practice and provide recommendations for diagnosis and treatment of persistent smell disorders following COVID-19.

Platelet-rich plasma for the treatment of COVID-19 related olfactory dysfunction: a systematic review.

INTRODUCTION: Olfactory Dysfunction (OD) is a prevalent issue with a significant number of cases attributed to COVID-19. This systematic review aimed to evaluate the effectiveness of platelet-rich plasma (PRP) in the treatment of COVID-19 related OD, including anosmia, hyposmia, and parosmia. METHODS: A comprehensive literature search was conducted using Medline, Scopus, Directory of Open Access Journals (DOAJ), and Google Scholar from inception until December 22, 2022. The eligibility criteria were confirmed COVID-19 patients with OD, whether it was measured objectively and/or subjectively, who received PRP treatment. The study followed a pre-specified protocol registered in PROSPERO (ID: CRD42023386803) and adhered to PRISMA guidelines. RESULTS: Four studies that enrolled 233 patients were included. The degree of improvement was assessed using threshold-discrimination-identification (TDI) scores at baseline and 1 and 2 months after PRP injection. Parosmia was assessed using the Visual Analog Scale (VAS) scores. Treatment of OD with PRP injections resulted in variable degrees of improvement. However, PRP injections can be considered safe, effective, and promising therapeutic options, as revealed by pooled studies. CONCLUSIONS: This systematic review indicated that PRP may be an effective treatment for COVID-19 related OD. However, additional large-scale studies are required to further investigate PRP efficacy in the treatment of OD following COVID-19.

Are YouTube videos on smell dysfunction a good source of information for patients seeking a cure for their illness?

OBJECTIVE: To conduct unbiased research into the quality and reliability of videos published on YouTube on the subject of smell dysfunction and treatment through two Ear, Nose, and Throat (ENT) specialists using three different tools. METHODS: The videos were separated into two groups (reliable: Group 1; non-reliable: Group 2) according to whether or not the content was scientifically reliable, proven, accurate, and useful, as determined by two ENT specialist physicians. The DISCERN reliability tool, Global quality scale (GQS), and JAMA scoring system were used as video scoring tools in the evaluations. RESULTS: Group 1 included 173 videos, and Group 2, 16 videos. The GQS (First ENT specialist) points were 3 (2-5) and GQS (Second ENT specialist) points were 3 (2-5) in Group 1, and 2 (2-3) and 2 (1-3) in Group 2, respectively (p = 0.0001). The points in the DISCERN and JAMA scoring systems were found to be higher in Group 1 than in Group 2 (p = 0.0001). CONCLUSION: Although the majority of videos on YouTube related to smell dysfunction are reliable, the number of unreliable videos is not inconsiderable. When videos related to medical information are accepted onto YouTube, weighting should be given to videos which include scientifically proven evidence uploaded by specialist professionals and institutions.

OBJETIVO: realizar una investigación imparcial sobre la calidad y la confiabilidad de los videos publicados en YouTube sobre el tema de la disfunción y el tratamiento del olfato, a través de dos especialistas en oído, nariz y garganta que utilizan tres herramientas diferentes. MÉTODOS: Los videos se separaron en dos grupos (confiables: Grupo 1; no confiables: Grupo 2) según si el contenido era o no científicamente confiable, probado, preciso y útil, según lo determinado por dos médicos especialistas en Otorrinolaringología. La herramienta de confiabilidad DISCERN, la escala de calidad global (GQS) y el sistema de puntuación JAMA se utilizaron como herramientas de puntuación de video en las evaluaciones. RESULTADOS: el Grupo 1 incluyó 173 videos y el Grupo 2, 16 videos. Los puntos GQS (Primer especialista en ORL) fueron 3 (2-5) y los puntos GQS (Segundo especialista en ORL) fueron 3 (2-5) en el Grupo 1, y 2 (2-3) y 2 (1-3) en el Grupo 2, respectivamente (p= 0.0001). Se encontró que los puntos en los sistemas de puntuación DISCERN y JAMA eran más altos en el Grupo 1 que en el Grupo 2 (p= 0.0001). CONCLUSIÓN: aunque la mayoría de los videos en YouTube relacionados con la disfunción del olfato son confiables, la cantidad de videos poco confiables no es despreciable. Cuando se aceptan videos relacionados con información médica en YouTube, se debe dar peso a los videos que incluyen evidencia científicamente probada y subidos por instituciones y profesionales especialistas.

Part Two: Perspectives on Olfactory and Gustatory Dysfunction Pathophysiology, Management, and Relevance to COVID-19: Current Approaches.

Context: The phenomena of olfactory and gustatory dysfunction disorders (OGD) are hardly unique to COVID-19. However, the widespread incidence of OGD as sequelae of COVID-19 has provoked rejuvenated interest in these long existing, but poorly studied maladies. Objective: This second of a three-part review discusses past and current approaches for treatment of OGD, not restricted to those that COVID-19 has caused, with the intention to lay a foundation for consideration of new paradigms for evaluation and management of OGD. Design: The researcher performed a narrative review by searching databases including PubMed, Sciencedirect, Google Scholar, Old Dominion University Libraries, and the websites of various medical journals. Searches included numerous combinations of keywords accompanied by the phrases, loss of sense of smell and taste, olfactory and gustatory dysfunction disorders, as well as the terms anosmia, parosmia, ageusia, and parageusia. Such keywords included viruses, bacteria, fungi, protozoa, parasites, infection, COVID-19, treatments, medications, steroids, supplements, nutrients, alternative medicine, acupuncture, olfactory training, clinical trials, cranial nerves, pathogenesis, pathophysiology, and etiology. Setting: The Liebell Clinic, Virginia Beach, VA, USA. Conclusions: The epidemiology and hypotheses of pathophysiology of post-COVID OGD has been addressed via numerous studies and reviews. However, extremely limited evidence of effective treatment for chronic OGD, in general, exists, Global demand for any treatment capable of reducing or resolving it is unprecedented. Past and present treatment approaches and recently initiated clinical trials, since the onset of the pandemic, have yet to yield any significant results.

Olfactory dysfunction in chronic rhinosinusitis: insights into the underlying mechanisms and treatments.

INTRODUCTION: Olfactory dysfunction (OD) is a typical symptom of chronic rhinosinusitis (CRS), which adversely affects the patient's quality of life and results in mood depression. Studies investigating the impairment of olfactory epithelium (OE) have indicated that inflammation-induced cell damage and dysfunction in OE plays a vital role in the development of OD. Consequently, glucocorticoids and biologics are beneficial in the management of OD in CRS patients. However, the mechanisms underlying OE impairment in CRS patients have not been fully elucidated. AREAS COVERED: This review focuses on mechanisms underlying inflammation-induced cell impairment in OE of CRS patients. Additionally, the methods used for detection of olfaction and both currently available and potentially new clinical treatments for OD are reviewed. EXPERT OPINION: Chronic inflammation in OE impairs not only olfactory sensory neurons but also non-neuronal cells that are responsible for regeneration and support for neurons. The current treatment for OD in CRS is mainly aimed at attenuating and preventing inflammation. Strategies for use of combinations of these therapies may achieve greater efficacy in restoration of the damaged OE and consequently better management of OD.

Design and Evaluation of a Potential Non-Invasive Neurostimulation Strategy for Treating Persistent Anosmia in Post-COVID-19 Patients.

A new pandemic was declared at the end of 2019 because of coronavirus disease 2019 (COVID-19). One of the effects of COVID-19 infection is anosmia (i.e., a loss of smell). Unfortunately, this olfactory dysfunction is persistent in around 5% of the world's population, and there is not an effective treatment for it yet. The aim of this paper is to describe a potential non-invasive neurostimulation strategy for treating persistent anosmia in post-COVID-19 patients. In order to design the neurostimulation strategy, 25 subjects who experienced anosmia due to COVID-19 infection underwent an olfactory assessment while their electroencephalographic (EEG) signals were recorded. These signals were used to investigate the activation of brain regions during the olfactory process and identify which regions would be suitable for neurostimulation. Afterwards, 15 subjects participated in the evaluation of the neurostimulation strategy, which was based on applying transcranial direct current stimulation (tDCS) in selected brain regions related to olfactory function. The results showed that subjects with lower scores in the olfactory assessment obtained greater improvement than the other subjects. Thus, tDCS could be a promising option for people who have not fully regained their sense of smell following COVID-19 infection.

Position paper on olfactory dysfunction: 2023

BACKGROUND: Since publication of the original Position Paper on Olfactory Dysfunction in 2017 (PPOD-17), the personal and societal burden of olfactory disorders has come sharply into focus through the lens of the COVID-19 pandemic. Clinicians, scientists and the public are now more aware of the importance of olfaction, and the impact of its dysfunction on quality of life, nutrition, social relationships and mental health. Accordingly, new basic, translational and clinical research has resulted in significant progress since the PPOD-17. In this updated document, we present and discuss currently available evidence for the diagnosis and management of olfactory dysfunction. Major updates to the current version include, amongst others: new recommendations on olfactory related terminology; new imaging recommendations; new sections on qualitative OD and COVID-19 OD; updated management section. Recommendations were agreed by all co-authors using a modified Delphi process. CONCLUSIONS: We have provided an overview of current evidence and expert-agreed recommendations for the definition, investigation, and management of OD. As for our original Position Paper, we hope that this updated document will encourage clinicians and researchers to adopt a common language, and in so doing, increase the methodological quality, consistency, and generalisability of work in this field.