Alpha-lipoic acid does not improve olfactory training results in olfactory loss due to COVID-19: a double-blind randomized trial.

OBJECTIVES: Olfactory loss is a recognized long-term dysfunction after Coronavirus Disease 2019 (COVID-19) infection. This investigation aimed to assess the effect of alpha-lipoic acid as an adjuvant treatment of olfactory training on the improvement of smell loss in post-COVID-19 patients. METHODS: This randomized controlled trial included 128 adult outpatients who had persistent smell loss for more than 3-months after COVID-19 infection. The participants were randomly allocated into two groups: the intervention treatment group, which received alpha-lipoic acid associated to olfactory training, and comparison treatment group, which received placebo pills associated to olfactory training. The participants were followed-up for 12-weeks. Olfactory dysfunction was assessed in terms of Visual Analog Scale (VAS), and the Connecticut Chemosensory Clinical Research Center (CCCRC) test for the Brazilian population. RESULTS: A total of 100 participants completed the follow-up period and were analyzed in this study. Both groups have improved CCCRC score (p = 0.000), olfactory threshold (p = 0.000), identification score (p = 0.000) and VAS score (p = 0.000) after 12-weeks follow-up. No significant differences were determined between the intervention and comparison treatment groups in CCCRC score (p = 0.63), olfactory threshold (p = 0.50), identification score (p = 0.96) and VAS score (p = 0.97). In all these criteria, comparison treatment group went slightly worse. At the endpoint of the study, the frequency of anosmia reduced to 2% in the intervention treatment group and to 7.8% in the comparison treatment group. Also, 16.8% of the intervention group' subjects, and 15.7% of comparison treatment group's patients reached normosmia. CONCLUSIONS: Overall, there was a strongly significant difference in olfactory function between baseline and endpoint for both groups. However, based on the lack of significant difference between the intervention treatment and the comparison treatment groups in terms of olfactory changes, our study appoints that the alpha-lipoic acid is not better than olfactory training alone to treat olfactory loss after COVID-19. LEVEL OF EVIDENCE: Level 2.

The brain functional connectivity alterations in traumatic patients with olfactory disorder after low-level laser therapy demonstrated by fMRI.

BACKGROUND: Low-level laser therapy (LLLT) has been clinically accepted to accelerate the nerve regeneration process after a nerve injury or transection. We aimed to investigate the neuronal basis and the influence of LLLT on brain functional networks in traumatic patients with olfactory dysfunction. METHODS: Twenty-four Patients with traumatic anosmia/hyposmia were exposed to pleasant olfactory stimuli during a block-designed fMRI session. After a 10-week period, patients as control group and patients who had completed the sessions of LLLT were invited for follow-up testing using the same fMRI protocol. Two-sample t-tests were conducted to explore group differences in activation responding to odorants (p-FDR-corrected <0.05). Differences of functional connectivity were compared between the two groups and the topological features of the olfactory network were calculated. Correlation analysis was performed between graph parameters and TDI score. RESULTS: Compared to controls, laser-treated patients showed increased activation in the cingulate, rectus gyrus, and some parts of the frontal gyrus. Shorter pathlength (p = 0.047) and increased local efficiency (p = 0.043) within the olfactory network, as well as decreased inter-network connectivity within the whole brain were observed in patients after laser surgery. Moreover, higher clustering and local efficiency were related to higher TDI score, as manifested in increased sensitivity to identify odors. CONCLUSIONS: The results support that low-level laser induces neural reorganization process and make new connections in the olfactory structures. Furthermore, the connectivity parameters may serve as potential biomarkers for traumatic anosmia or hyposmia by revealing the underlying neural mechanisms of LLLT.

Effect of any form of steroids in comparison with that of other medications on the duration of olfactory dysfunction in patients with COVID-19: A systematic review of randomized trials and quasi-experimental studies.

BACKGROUND: The life quality of about two-thirds of patients with COVID-19 is affected by related olfactory dysfunctions. The negative impact of olfactory dysfunction ranged from the decreased pleasure of eating to impaired quality of life. This research aimed to provide a comprehensive understanding of the effects of corticosteroid treatments by comparing that to other currently available treatments and interventions. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist's 27-point checklist was used to conduct this review. PubMed (Public/Publisher MEDLINE), PubMed Central and EMBASE (Excerpta Medica Database) databases were conveniently selected and Boolean search commands were used for a comprehensive literature search. Five core search terms were "effects of treatments", " COVID-19-related olfactory dysfunction", "corticosteroids", "treatments" and "interventions". The reporting qualities of the included studies were appraised using JBI (Joanna Briggs Institute) appraisal tools. The characteristics of the 21 experimental studies with a total sample (of 130,550) were aggregated using frequencies and percentages and presented descriptively. The main interventions and their effects on the duration of the COVID-19-related olfactory dysfunction were narratively analyzed. RESULTS: Among patients with COVID-19, the normal functions of the olfactory lobe were about 23 days earlier to gain with the treatments of fluticasone and triamcinolone acetonide nasal spray compared with that of mometasone furoate nasal spray and oral corticosteroid. The smell loss duration was reduced by fluticasone and triamcinolone acetonide nasal spray 9 days earlier than the inflawell syrup and 16 days earlier than the lavender syrup. The nasal spray of corticosteroids ended the COVID-19-related smell loss symptoms 2 days earlier than the zinc supplementation, about 47 days earlier than carbamazepine treatment and was more effective than palmitoylethanolamide (PEA) and luteolin and omega-3 supplementations and olfactory training. Treatment with oral corticosteroid plus olfactory training significantly improved Threshold, Discrimination and Identification (TDI) scores compared with olfactory training alone. A full dose of the COVID-19 vaccination was not uncertain to reduce the COVID-19-related smell loss duration. CONCLUSION: Corticosteroid treatment is effective in reducing the duration of COVID-19-related smell loss and olfactory training, the basic, essential and effective intervention, should be used as a combination therapy.

Coronavirus disease 2019 related parosmia: an exploratory survey of demographics and treatment strategies.

OBJECTIVE: To investigate the clinical features, therapeutic efficacy and symptom time course of post-coronavirus disease 2019 parosmia. METHODS: A 22-item online questionnaire was distributed to AbScent research group and Facebook coronavirus disease 2019 anosmia group adult members to assess clinical features, interventions and their subjective efficacy for parosmia. RESULTS: A total of 209 participants (86 per cent females) reported: smell loss on average 3 days after coronavirus symptoms, recovery 4 weeks later, and first parosmia symptoms 12 weeks post infection. Respondents reported 10 per cent body weight loss, and listed onion and garlic as significant parosmia triggers. Regarding quality of life, depression was the most cited item (54 per cent). Smell training was trialled by 74 per cent of participants, followed by nasal corticosteroid spray (49 per cent). Stellate ganglion block, trialled by 16 per cent of respondents, had the highest reported improvement (45 per cent), with 21 per cent reporting a sustained benefit - the highest rate amongst registered treatment options. CONCLUSION: Post-coronavirus parosmia has a significant impact and remains challenging to treat. Stellate ganglion block appears to be successful relative to other reported treatments. Further research into the pathophysiology, efficacy and mechanism of stellate ganglion block effect is warranted.

The Effect of Chinese Herbal Medicine on Traumatic Anosmia: A Prospective, Randomized Clinical Trial.

OBJECTIVE: Chinese herbal medicine (CHM) has been implemented as a form of treatment for olfactory dysfunction. In this study, we aimed to use a tailored Guizhi decoction for the treatment of traumatic olfactory dysfunction. METHODS: Patients who had lost olfactory function after experiencing head trauma and whose olfactory function was anosmic were selected. The eligible patients were randomly assigned to two groups. In the CHM group, a tailored Guizhi decoction was prescribed, with patients also undergoing olfactory training (OT). In the OT group, patients performed OT only. The olfactory function of each patient was evaluated by both the phenyl ethyl alcohol (PEA) odor detection threshold test and the traditional Chinese version of the University of Pennsylvania Smell Identification Test (TC-UPSIT), at both 3 and 6 months after the completion of treatment. RESULTS: A total of 38 patients in the CHM group and 40 in the OT group completed the study. The TC-UPSIT scores of patients slightly rose after treatment in both the CHM and OT groups. Nevertheless, there were no significant differences in TC-UPSIT scores before and after treatment in both groups. However, the PEA thresholds improved significantly in both CHM and OT groups (p = 0.005 and 0.016, respectively). Of note, there were no significant differences in threshold or identification scores between the CHM and OT groups. CONCLUSION: Our results show that adding a tailored Guizhi decoction to OT conferred a limited benefit to the olfactory function of patients experiencing traumatic anosmia. LEVEL OF EVIDENCE: 2 Laryngoscope, 133:1473-1479, 2023.

Efficacy of Combined Visual-Olfactory Training With Patient-Preferred Scents as Treatment for Patients With COVID-19 Resultant Olfactory Loss: A Randomized Clinical Trial.

Importance: The number of olfactory dysfunction cases has increased dramatically because of the COVID-19 pandemic. Identifying therapies that aid and accelerate recovery is essential. Objective: To determine the efficacy of bimodal visual-olfactory training and patient-preferred scents vs unimodal olfactory training and physician-assigned scents in COVID-19 olfactory loss. Design, Setting, and Participants: This was a randomized, single-blinded trial with a 2-by-2 factorial design (bimodal, patient preferred; unimodal, physician assigned; bimodal, physician assigned; unimodal, patient preferred) and an independent control group. Enrollment occurred from February 1 to May 27, 2021. Participants were adults 18 to 71 years old with current olfactory loss defined as University of Pennsylvania Smell Identification Test (UPSIT) score less than 34 for men and less than 35 for women and duration of 3 months or longer. Olfactory loss was initially diagnosed within 2 weeks of COVID-19 infection. Interventions: Participants sniffed 4 essential oils for 15 seconds with a 30-second rest in between odors for 3 months. Participants in the physician-assigned odor arms trained with rose, lemon, eucalyptus, and clove. Participants randomized to the patient-preferred arms chose 4 of 24 available scents. If assigned to the bimodal arm, participants were shown digital images of the essential oil they were smelling. Main Outcomes and Measures: The primary end point was postintervention change in UPSIT score from baseline; measures used were the UPSIT (validated, objective psychometric test of olfaction), Clinical Global Impressions Impression-Improvement (CGI-I; self-report improvement scale), and Olfactory Dysfunction Outcomes Rating (ODOR; olfaction-related quality-of-life questionnaire). Results: Among the 275 enrolled participants, the mean (SD) age was 41 (12) years, and 236 (86%) were female. The change in UPSIT scores preintervention to postintervention was similar between the study arms. The marginal mean difference for change in UPSIT scores preintervention to postintervention between participants randomized to patient-preferred vs physician-assigned olfactory training was 0.73 (95% CI, -1.10 to 2.56), and between participants randomized to bimodal vs unimodal olfactory training was 1.10 (95% CI, -2.92 to 0.74). Five (24%) participants in the control arm had clinically important improvement on UPSIT compared with 18 (53%) in the bimodal, patient-preferred arm for a difference of 29% (95% CI, 4%-54%). Four (19%) participants in the control group self-reported improvement on CGI-I compared with 12 (35%) in the bimodal, patient-preferred arm for a difference of 16% (95% CI, -7% to 39%). The mean change in ODOR score preintervention to postintervention was 11.6 points (95% CI, 9.2-13.9), which was not deemed clinically important nor significantly different between arms. Conclusions and Relevance: Based on the change in UPSIT scores, this randomized clinical trial did not show any difference between intervention arms, but when exploring within-patient change in UPSIT as well as self-reported impression of improvement, active interventions were associated with larger improvement than controls with a potential advantage of bimodal intervention. While not definitive, these results suggest that patients with COVID-19 olfactory loss may benefit from bimodal visual-olfactory training with patient-preferred scents. Trial Registration: ClinicalTrials.gov Identifier: NCT04710394.

Resultados terapêuticos da homeopatia em pacientes suspeitos ou confirmados de COVID-19: um estudo longitudinal prospectivo / Therapeutic results of homeopathy in suspected or confirmed COVID-19 patients: a longitudinal study

A infecção humana causada pelo vírus SARS-CoV-2 (COVID-19), diagnosticada como pneumonia de causa desconhecida originalmente na cidade de Wuhan (China), foi considerada como pandemia pela Organização Mundial da Saúde. Com a inexistência inicial de uma vacina para proteção dos sadios, foi adotada a estratégia de isolamento social e tratamento com medidas de suporte geral e/ou avançado. Neste contexto, coube investigar a contribuição da terapêutica homeopática no enfrentamento da doença, notadamente no alívio dos sintomas desconfortáveis por ela provocados em sua fase inicial, com acompanhamento e registro dos resultados obtidos pelos médicos homeopatas. MÉTODO: Este estudo coletou, durante o período de maio a setembro de 2020 (após aprovação pelo CEP), informações de pacientes diagnosticados com a doença, tratados por médicos homeopatas com medicamentos homeopáticos escolhidos de acordo com a sintomatologia apresentada pelo paciente. Foram avaliados os efeitos no estado de saúde do paciente, por meio de escores e escalas clínicas, bem como aspectos relacionados à segurança do medicamento, variação na duração da doença e medicamentos mais associados a eventuais sucessos terapêuticos. Questionário padronizado e específico para a COVID-19 foi elaborado e e aplicado para preenchimento dos médicos colaboradores do estudo durante o acompanhamento dos pacientes. Os dados foram armazenados em planilhas eletrônicas e analisados com técnicas estatísticas descritivas e inferenciais. Os pacientes selecionados eram colaboradores do Hospital Santo Antônio - Obras Sociais Irmã Dulce (OSID) e foram submetidos a uma avaliação preliminar presencial no ambulatório de Otorrinolaringologia deste hospital. As consultas homeopáticas foram realizadas por plataforma de Telemedicina para seguimento e acompanhamento do caso. Foram avaliados 116 colaboradores, com faixa etária que variou entre 21 e 66 anos, sendo a média de idade 38 anos; destes, 84 (72%) eram do gênero feminino e 32 (16%) gênero masculino; 53 pacientes (70% dos colaboradores atendidos) eram profissionais da saúde (médicos, enfermeiros e técnicos de enfermagem); 63 (30%) eram colaboradores de áreas administrativas ou técnicas; 50 pacientes tinham critérios para inclusão no grupo de risco (43%). Quanto ao resultado do RT-PCR: 58 pacientes (50%) tiveram RT-PCR detectado (confirmados); 58 pacientes (50%) tiveram RT-PCR não-detectado - destes, 18 pacientes (31%) apresentaram anosmia em sua evolução. Dos 116 pacientes do critério de inclusão, 77 estavam incluídos na síndrome clássica da COVID19. Destes 77 colaboradores, 3 não usaram o medicamento homeopático (N=74). Os medicamentos homeopáticos mais indicados foram: Arsenicum album (42%); Bryonia (24%), Phosphorus (15%); Gelsemium (15%); Pulsatilla (2%); outros (4%). O Score médio de sintomas antes do tratamento foi 12,27 e após o tratamento foi 0,52 (p < xxxxx). Dos 57 pacientes que tiveram anosmia, houve recuperação total em 43 (75%) dos casos no momento da reavaliação. O tempo médio decorrido entre o uso da medicação homeopática e a recuperação dos sintomas foi de 9 dias. Apenas 3 pacientes (3,9%) necessitaram de internamento hospitalar sem necessidade de intubação, sendo 2 deles pertencentes ao grupo de risco. apesar destes resultados serem parciais (pois ainda existem sujeitos da pesquisa ainda em fase de avaliação), os resultados sugerem que o tratamento homeopático promoveu o restabelecimento do quadro infeccioso sem necessidade de internamento em 97% dos pacientes. A anosmia teve recuperação completa em 75% dos pacientes. Arsenicum album, Bryonia e Phosphorus foram os medicamentos predominantemente eleitos para o tratamento, o que corrobora com outros estudos homeopáticos.

The human infection caused by the SARS-CoV-2 virus (COVID-19), originally diagnosed as pneumonia of unknown cause in the city of Wuhan (China), was considered a pandemic by the World Health Organization. With the initial lack of a vaccine to protect healthy people, the strategy relating to social isolation and treatment with general and/or advanced support measures was adopted. In this context, it was necessary to investigate the contribution of homeopathic therapy in coping with the disease, particularly in terms of relieving the uncomfortable symptoms caused by it in its initial phase, with monitoring and recording of the results obtained by homeopathic physicians. METHOD: This study collected information from patients diagnosed with the disease, treated by homeopathic physicians with homeopathic medications chosen according to the symptoms manifested by the patient, from May to September 2020 (after approval by the REC). The effects on the health conditions of patients were assessed using clinical scores and scales, as well as aspects related to the safety of the medication, variations in the duration of the disease and the medications most associated with any therapeutic successes. A standardized questionnaire specific to COVID-19 was drawn up and filled in by the physicians who collaborated in the study during patient monitoring. The data was stored in electronic spreadsheets and analyzed using descriptive and inferential statistical techniques. The selected patients were employees of Hospital Santo Antônio - Obras Sociais Irmã Dulce (OSID) and underwent a preliminary in-person assessment at the otolaryngology outpatient clinic of this hospital. The homeopathic consultations were carried out via a telemedicine platform to follow-up and monitor the case. A total of 116 employees were assessed, ranging in age from 21 to 66, with the average age being 38; of these, 84 (72%) were females and 32 (16%) males; 53 patients (70% of the employees cared for) were health care professionals (physicians, nurses and nursing technicians); 63 (30%) were employees from administrative or technical areas; 50 patients met the criteria for inclusion in the risk group (43%). As for the RT-PCR result: 58 patients (50%) had RT-PCR detected (confirmed); 58 patients (50%) had RT-PCR not detected - of these, 18 patients (31%) had anosmia during their evolution. Of the 116 patients who met the inclusion criteria, 77 were included in the classic COVID-19 syndrome. Of these 77 collaborators, 3 did not use homeopathic medication (N=74). The most indicated homeopathic medications were: Arsenicum album (42%); Bryonia (24%), Phosphorus (15%); Gelsemium (15%); Pulsatilla (2%); others (4%). The average symptom score before treatment was 12.27 and after treatment was 0.52 (p < xxxxx). Of the 57 patients who had anosmia, there was full recovery in 43 (75%) of the cases at the time of reassessment. The average time elapsed between the use of homeopathic medication and the recovery of symptoms was 9 days. Only 3 patients (3.9%) required hospitalization without the need for intubation, 2 of whom belonged to the risk group. Although these results are partial (as there are still research subjects in the evaluation phase), the results suggest that homeopathic treatment promoted the re-establishment of the infectious condition without the need for hospitalization in 97% of the patients. Anosmia recovered completely in 75% of the patients. Arsenicum album, Bryonia and Phosphorus were the drugs predominantly chosen for treatment, which corroborates other homeopathic studies.

Changes in olfaction & quality of life following standard medical therapy in patients with intermittent & persistent allergic rhinitis.

Background & objectives: Allergic rhinitis (AR) is an inflammatory disease prevalent worldwide which can affect both olfaction and quality of life (QoL). The objective of the present study was to assess olfaction and QoL changes in patients with AR before and after medical therapy. Methods: Adult participants (>18 yr) with AR were recruited for this study. These patients prospectively underwent olfaction testing using the modified Connecticut Chemosensory Clinical Research Centre Test and QoL assessment using Rhinoconjunctivitis QoL Questionnaire (RQLQ) before and after standard medical therapy with topical steroids and/antihistaminics. Results: Of the 150 patients recruited, 72 per cent had intermittent AR. The symptom of hyposmia was present in 34 patients (22.7%) and was more prevalent in patients with moderate-to-severe type of AR (P<0.001). However, olfaction testing revealed hyposmia/anosmia in 44 patients (29.3%). Mean composite olfaction scores were significantly higher in patients with mild AR compared to moderate/severe AR (P=0.026). The pre-therapy mean composite olfaction score in the 34 patients with olfaction disturbances was 3.1 standard deviation (±1.06 SD). Following therapy, the mean composite olfaction score rose to 4.3 (±1.34 SD) and this change was found to be significant (P<0.001). Mean pre-therapy RQLQ scores were 2.87 (0.06-5.33) overall. Significant improvement was also found in RQLQ scores following therapy (P<0.001). Mean RQLQ scores were significantly lower in those with moderate-to-severe AR (P<0.001) as well as those with intermittent AR (P=0.004). Nine patients had persistently high RQLQ scores after medical therapy. Interpretation & conclusions: Both olfaction and QoL showed significant improvement after medical therapy in Indian adults with AR. In those patients who do not improve, other causes must be sought for the persistent symptoms.

COVID-19 Induced Taste Dysfunction and Recovery: Association with Smell Dysfunction and Oral Health Behaviour.

Background and Objectives: Disruption to taste and smell are common symptoms of COVID-19 infection. The current literature overlooks taste symptoms and tends to focus on the sense of smell. Persisting cases (>28 days) of taste dysfunction are increasingly recognised as a major future healthcare challenge. This study focuses on the severity and recovery of COVID-19 induced taste loss and association with olfactory symptoms, lifestyle and oral health factors. Materials and Methods: This study was a cross-sectional survey comparing 182 rapid taste recovery participants (≤28 days) with 47 participants with prolonged taste recovery >28 days. Analyses of taste loss in association with smell loss, age, sex, illness severity, diet, BMI, vitamin-D supplementation, antidepressants, alcohol use, smoking, brushing frequency, flossing, missing teeth, appliances and number of dental restorations were conducted. Differences in the severity of the loss of sour, sweet, salt, bitter and umami tastes were explored. Results: Both the severity and the duration of taste and smell loss were closely correlated (p < 0.001). Salt taste was significantly less affected than all other taste qualities (p < 0.001). Persisting taste loss was associated with older age (mean ± 95% CI = 31.73 ± 1.23 years vs. 36.66 ± 3.59 years, p < 0.001) and reduced likelihood of using floss (odds ratio ± 95% CI = 2.22 (1.15−4.25), p = 0.047). Conclusions: Smell and taste loss in COVID-19 are closely related, although a minority of individuals can experience taste or smell dysfunction in the absence of the other. The taste of salt may be less severely affected than other taste qualities and future work exploring this finding objectively is indicated. The association of flossing with rapid taste recovery adds to the growing evidence of a link between good periodontal health and favourable COVID-19 outcomes.

Could melatonin have a potential adjuvant role in the treatment of the lasting anosmia associated with COVID-19? A review.

INTRODUCTION: Anosmia, the loss of the sense of smell, is usually associated with rhinopathies and has been reported as a common symptom of COVID-19. There is no specific drug to treat this condition, although some evidence suggests that melatonin could promote the recovery of olfactory sensory neurons. METHODS: We set out to perform a narrative review to synthesize the current evidence in this area in respect of our hypothesis that melatonin may be linked with anosmia and play a part in oxidative stress and the regulation of inflammation. The main electronic databases (MEDLINE/PubMed, Embase, and Cochrane) were searched. RESULTS: The search produced 26 articles related to our hypothesis. Some studies examined issues related to melatonin's effects and its use as adjuvant therapy for COVID-19. Despite some studies suggesting that melatonin may have potential in the treatment of COVID-19, to the best of our knowledge, there have been no trials that have used it to treat anosmia associated with the disease. Few articles identified proposed that melatonin might have an effect on olfactory cells. DISCUSSION: Further experimental and clinical research on the role of circadian melatonin in the olfactory system is warranted. This will provide evidence of the use of melatonin in the management of anosmia. A number of identified studies suggest that the imbalanced release of melatonin by the pineal gland associated with sleep disturbance may play a role in anosmia, although the specific pathway is not yet entirely clear. This may be a base for further research into the potential role of melatonin as adjuvant treatment of anosmia.

Photobiomodulation therapy for treatment olfactory and taste dysfunction COVID-19-related: A case report.

It is postulated that the inflammatory process resulting from SARS-CoV-2 infection is the main cause of smell and taste dysfunctions in patients. In view of this, photobiomodulation, due to its anti-inflammatory and antioxidant effects, may be a promising therapeutic modality to treat these disorders. In the present case report, we observed clinical improvement in the symptoms of anosmia and ageusia related to COVID-19 after treatment with photobiomodulation. Due to the inflammatory nature of COVID-19 and the anti-inflammatory effects, photobiomodulation antioxidants already proven in the literature make it a promising therapeutic modality, especially sequela COVID-related, including olfactory (anosmia) and taste (ageusia) dysfunction. In the present case report, the patient's olfactory and gustatory functions were re-established after 10 treatment sessions with photobiomodulation.

A Houttuynia cordata-based Chinese herbal formula improved symptoms of allergic rhinitis during the COVID-19 pandemic.

BACKGROUND: The symptoms of coronavirus disease 2019 (COVID-19) such as hyposmia, rhinorrhea, nasal obstruction, and cough are similar to those of chronic allergic rhinitis (AR). Such symptoms can easily lead AR patients to unnecessary anxiety, misdiagnosis, and invasive diagnostic tests in the COVID-19 pandemic. Interleukin-6 (IL-6) is an important mediator for chronic AR and plays a crucial role in the inflammation of COVID-19. Houttuynia cordata (HC) has been shown to reduce nasal congestion and swelling by suppressing the activation of IL-6 and is used to fight COVID-19. A novel HC-based Chinese herbal formula, Zheng-Yi-Fang (ZYF), was developed to test effects on nasal symptoms of patients with AR in the COVID-19 pandemic. METHODS: Participants aged between 20 and 60 years with at least a 2-year history of moderate to severe perennial AR were enrolled. Eligible participants were randomly allocated to either the intervention group (taking ZYF) or the control group (using regular western medicine) for 4 weeks. The Chinese version of the Rhinosinusitis Outcome Measures was used to evaluate impacts on quality of life and nasal symptoms of participants with AR. In addition, the effect of ZYF on lipopolysaccharide (LPS)-induced IL-6 was investigated. RESULTS: Participants with AR taking ZYF improved their symptoms of nasal obstruction, nasal secretion, hyposmia, and postnasal drip in comparison with those of the control group. Meanwhile, ZYF exhibited inhibition of IL-6 secretion in the LPS-induced inflammatory model. CONCLUSION: ZYF has potential effects to relieve nasal symptoms for AR during the COVID-19 pandemic.

Retracted: Whole-Body Cryotherapy as an Innovative Treatment for COVID 19-Induced Anosmia-Hyposmia: A Feasibility Study.

The article entitled, "Whole-Body Cryotherapy as an Innovative Treatment for COVID 19-Induced Anosmia-Hyposmia: A Feasibility Study," by Legrand FD, Polidori G, Beaumont F, Bouchet B, Morin A, Derruau S, and Brenet E (Epub ahead of print Jan 13, 2022; DOI: 10.1089/jicm.2021.0254) is officially retracted at the request of the authors. This request came after the paper had undergone full peer review, three rounds of revisions, acceptance, page proofs, and ultimately, online publication. The Methods section of the published paper states that the study had "secured University ethics clearance…"1 but the authors explained that, "after re-discussion and internal reassessment, it appears clearly that this study required, according to French law, the approval of a specific committee known as the '[C]ommittee for the [P]rotection of [P]ersons (CPP)' and not a simple ethical agreement. For this reason, [we] request, in good faith, that the article be retracted. We apologize for this delay in taking a position, but this study gave rise to a re-discussion with our peers of the methodology which led us to realize our error 'a posteriori.'" The authors' respective institutions have been notified by the publisher. Journal of Integrative and Complementary Medicine is committed to upholding the rigors of scientific publishing and the veracity of the literature. Reference 1. Legrand FD, Polidori G, Beaumont F, et al. Whole-body cryotherapy as an innovative treatment for COVID 19-induced anosmia-hyposmia: a feasibility study. Epub ahead of print Jan 13, 2022; DOI: 10.1089/jicm.2021.0254.

Relationship between Recovery from COVID-19-Induced Smell Loss and General and Oral Health Factors.

Background and Objectives: Loss of smell is one of the strongest predictors of coronavirus disease 2019 (COVID-19) and can persist long after other symptoms have resolved. "Long" cases (>28 days) of smell dysfunction present future challenges to medical and dental professionals, as there is a lack of evidence on the causes and any exacerbating or relieving factors. This study aimed to explore the persistence of COVID-19-induced smell loss and association with physical, lifestyle and oral health factors. Materials and Methods: This study was a cross-sectional survey of 235 participants. Recovery of smell was explored, comparing rapid recovery (≤28 days) with prolonged recovery (>28 days). Associative factors included age, sex, illness severity, diet, BMI, vitamin D supplementation, antidepressants, alcohol use, smoking, brushing frequency, flossing, missing teeth, appliances and number of dental restorations. Results: Smell loss showed 87% resolution within 30 days. Prolonged smell loss was significantly associated with older age (mean ± 95%, CI = 31.53 ± 1.36 years for rapid recovery vs. mean ± 95%, CI = 36.0 ± 3 years for prolonged recovery, p = 0.003) and increased self-reported illness severity (mean ± 95%, CI = 4.39 ± 0.27 for rapid recovery vs. 5.01 ± 0.54 for prolonged recovery, p = 0.016). Fisher's exact test revealed flossing was associated with rapid recovery, with flossers comprising 75% of the rapid-recovery group, compared to 56% in the prolonged-recovery group (odds ratio ± 95%, CI = 2.26 (1.23-4.15), p = 0.01). All other factors were not significantly associated (p > 0.05). Conclusions: Increased age and illness severity were associated with prolonged smell recovery. Use of floss was the only modifiable factor associated with rapid recovery of smell loss. As 87% of cases resolve within 30 days, future studies may benefit from targeted recruitment of individuals experiencing prolonged sense loss. This would increase statistical confidence when declaring no association with the other factors assessed, avoiding type II errors.

Acupuncture is associated with a positive effect on odour discrimination in patients with postinfectious smell loss-a controlled prospective study.

INTRODUCTION: Smell disorders are common in the general population and occur e.g., after infections, trauma or idiopathically Treatment strategies for smell loss range from surgery, medication to olfactory training, depending on the pathology, but they are limited This study examined the effect of acupuncture on olfactory function. METHODS: Sixty patients with smell loss following infections of the upper respiratory tract were included in this investigation Half of the study group were randomly assigned to verum acupuncture and the other half to sham acupuncture Olfaction was measured by means of the "Sniffin' Sticks" test battery (odour threshold, discrimination and identification). RESULTS: Compared to sham acupuncture, verum was associated with an improvement of smell function as measured by the TDI score (p = 0.039) The improvement was largely determined by improvement in odour discrimination, and was significantly better in patients with a shorter duration of the disorder. CONCLUSION: The present results suggest that acupuncture is an effective supplementary treatment option for patients with olfactory loss.

Follow Your Nose: A Key Clue to Understanding and Treating COVID-19.

This paper suggests that ATP release induced by the SARS-CoV-2 virus plays a key role in the genesis of the major symptoms and complications of COVID-19. Infection of specific cells which contain the Angiotensin-Converting Enzyme 2 (ACE2) receptor results in a loss of protection of the Mineralocorticoid Receptor (MR). Local activation by cortisol stimulates the release of ATP initially into the basolateral compartment and then by lysosomal exocytosis from the cell surface. This then acts on adjacent cells. In the nose ATP acts as a nociceptive stimulus which results in anosmia. It is suggested that a similar paracrine mechanism is responsible for the loss of taste. In the lung ATP release from type 2 alveolar cells produces the non-productive cough by acting on purinergic receptors on adjacent neuroepithelial cells and activating, via the vagus, the cough reflex. Infection of endothelial cells results in the exocytosis of WeibelPalade bodies. These contain the Von Willebrand Factor responsible for micro-clotting and angiopoietin-2 which increases vascular permeability and plays a key role in the Acute Respiratory Distress Syndrome. To test this hypothesis this paper reports proof of concept studies in which MR blockade using spironolactone and low dose dexamethasone (SpiDex) was given to PCR-confirmed COVID-19 patients. In 80 patients with moderate to severe respiratory failure 40 were given SpiDex and 40 conventional treatment with high dose dexamethasone (HiDex). There was 1 death in the HiDex group and none in the SpiDex. As judged by clinical, biochemical and radiological parameters there were clear statistically significant benefits of SpiDex in comparison to HiDex. A further 20 outpatients with COVID-19 were given SpiDex. There was no control group and the aim was to demonstrate safety. No adverse effects were noted and no patient became hyperkalaemic. 90% were asymptomatic at 10 days. The very positive results suggest that blockade of the MR can produce major benefit in COVID19 patients. Further larger controlled studies of inpatients and outpatients are required not only for SARS-CoV-2 infection per se but also to determine if this treatment affects the incidence of Long COVID.

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.

Does serotonin deficiency lead to anosmia, ageusia, dysfunctional chemesthesis and increased severity of illness in COVID-19?

Different mechanisms forwarded to understand anosmia and ageusia in coronavirus patients are not adequate to explain reversible anosmia and ageusia, which are resolved quickly. In addition, the reason behind the impaired chemesthetic sensations in some coronavirus patients remains unknown. In the present paper it is proposed that SARS-CoV-2 patients suffer from depletion of tryptophan, as ACE2, a key element in the process of absorption of tryptophan from the food, is significantly reduced in the patients as coronavirus uses ACE2 as the receptor to enter the host cells. The tryptophan depletion leads to a deficit of serotonin (5-HT) in SARS-COV-2 patients because tryptophan is the precursor in the synthesis of 5-HT. Such 5-HT deficiency can explain anosmia, ageusia and dysfunctional chemesthesis in COVID-19, given the fact that 5-HT is an important neuromodulator in the olfactory neurons, taste receptor cells and transient receptor potential channels (TRP channels) involved in chemesthesis. In addition, 5-HT deficiency worsens silent hypoxemia and depresses hypoxic pulmonary vasoconstriction leading to increased severity of the disease. Also, the levels of anti-inflammatory melatonin (synthesized from 5-HT) and nicotinamide adenine dinucleotide (NAD+, produced from niacin whose precursor is the tryptophan) might decrease in coronavirus patients resulting in the aggravation of the disease. Interestingly, selective serotonin reuptake inhibitors (SSRIs) may not be of much help in correcting the 5-HT deficiency in COVID-19 patients, as their efficacy goes down significantly when there is depletion of tryptophan in the system. Hence, tryptophan supplementation may herald a radical change in the treatment of COVID-19 and accordingly, clinical trials (therapeutic / prophylactic) should be conducted on coronavirus patients to find out how tryptophan supplementation (oral or parenteral, the latter in severe cases where there is hardly any absorption of tryptophan from the food) helps in curing, relieving or preventing the olfactory, gustatory and chemesthetic dysfunctions and in lessening the severity of the disease.