Smell loss is associated with cognitive impairment in amyotrophic lateral sclerosis patients.

BACKGROUND: Smell loss significantly impacts the quality of life in patients. However, there is limited research on smell loss in individuals with amyotrophic lateral sclerosis (ALS), and the correlation between smell loss and cognitive impairment is unclear. This study aimed to investigate the correlation between smell loss and cognition impairment in ALS patients. METHODS: The study included 216 ALS patients. The Edinburgh Cognitive and Behavioural ALS Screen (ECAS) and smell identification test specifically for the Chinese population (CSIT) were administered to evaluate participants' cognitive and olfactory function, respectively. RESULTS: After covarying for age, sex, BMI, education level, degree of hunger, dietary bias, eagerness for food, stress, smoking status, alcohol consumption, and upper respiratory tract infection (URTI) or rhinitis, CSIT scores were significantly correlated with ECAS scores (r = 0.162, p = 0.028), especially the ALS-specific scores (r = 0.158, p = 0.031). Even after excluding patients with URTI or rhinitis, the results were similar. CSIT scores were significantly correlated with ECAS scores (r = 0.224, p = 0.011), especially the ALS-specific scores (r = 0.205, p = 0.019). CONCLUSION: In patients with ALS, smell loss is significantly correlated with cognitive impairment, particularly frontotemporal dysfunction. Cognitive dysfunction may lead to worse olfactory performance in ALS patients.

Effect of drug therapies on self-reported chemosensory outcomes after COVID-19.

Objective: The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on self-reported alterations in taste and/or smell function. Methods: Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019 (post-COVID-19) chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the disease. The dependent measure-self-reported total recovery of chemosensory symptoms-was subjected to stepwise logistic regression. Independent predictors included demographic and clinical variables, in addition to specific medications used to mitigate disease symptoms (i.e., systemic corticosteroids, oseltamivir, vitamin C, ibuprofen, hydroxychloroquine, azithromycin, ivermectin, nitazoxanide, anticoagulants, and zinc). Results: The median time between COVID-19 symptom onset and the interviews was 81 days (interquartile range: 60-104). Of the 714 subjects, 249 (34.9%) reported total recovery of their chemosensory function; 437 (61.2%) had at least one treatment since the beginning of the disease. Women and those with more comorbidities had undergone more treatments. The recovery rates of the treated and nontreated groups did not differ significantly. Nonetheless, respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell recovery. Those who took oral zinc were less likely to improve. Conclusions: No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal, although nitrazoxide trended in a positive direction. Oral zinc had a negative effect on the reported recovery of these senses.

The olfactory diary: Tracking awareness and consciousness of the sense of smell throughout the day.

Objectives: The aim of the present study was to follow the daily course of patients with olfactory dysfunction and healthy controls and to assess (i) how many times a day, (ii) at which time, and (iii) in which aspect of daily life participants are conscious about their sense of smell. Methods: In this longitudinal study, 49 patients with smell loss and 30 healthy participants were enrolled. Olfactory function was assessed using the Sniffin' Sticks. All participants received paper diaries designed for a 14-day period, featuring 12 rows representing 12 daily hours and six columns for various daily life aspects. They were instructed to mark their awareness of smell by indicating the relevant row and column in the diary. Following the return of the diaries, a second olfactory test was conducted within the patient group. Results: On average, patients were consciously aware of their sense of smell around 8 times daily, while healthy participants noted it about 6.5 times a day. Both groups primarily focused on their sense of smell during activities related to "eating," followed by considerations in "social life" and "personal hygiene." Interestingly, distinct patterns emerged: patients peaked in awareness at 8 a.m. and 7 p.m., whereas healthy individuals showed peaks at 6 a.m., 12 p.m., and 7 p.m. Despite regular diary use, we observed no improvement in patients' olfactory function or related quality of life. Conclusion: The olfactory diary is a valuable tool unveiling individual smell awareness patterns in patients with smell loss, aiding in counseling and patient management. Level of Evidence: 4.

Platelet-Rich Plasma (PRP) in the Treatment of Long COVID Olfactory Disorders: A Comprehensive Review.

Background: Long COVID has brought numerous challenges to healthcare, with olfactory dysfunction (OD) being a particularly distressing outcome for many patients. The persistent loss of smell significantly diminishes the affected individual's quality of life. Recent attention has been drawn to the potential of platelet-rich plasma (PRP) therapy as a treatment for OD. This comprehensive review aims to evaluate the effectiveness of PRP therapy in ameliorating OD, especially when associated with long-term COVID-19. Methods: We executed a comprehensive search of the literature, encompassing clinical trials and observational studies that utilized PRP in treating OD limited to COVID-19. We retrieved and comprehensively discussed data such as design, participant demographics, and reported outcomes, focusing on the efficacy and safety of PRP therapy for OD in COVID-19 patients. Results: Our comprehensive analysis interestingly found promising perspectives for PRP in OD following COVID-19 infection. The collective data indicate that PRP therapy contributed to a significant improvement in olfactory function after COVID-19 infection. Conclusions: The evidence amassed suggests that PRP is a promising and safe therapeutic option for OD, including cases attributable to Long COVID-19. The observed uniform enhancement of olfactory function in patients receiving PRP highlights the necessity for well-designed, controlled trials. Such studies would help to refine treatment protocols and more definitively ascertain the efficacy of PRP in a broader, more varied patient cohort.

A Study on the Impact of the COVID-19 Pandemic on the Aetiology of Paediatric Olfactory Dysfunction.

INTRODUCTION: Although previous studies have examined olfactory dysfunction in children, the novel coronavirus SARS-CoV-2 has certainly had an unprecedented effect on their olfaction, which could not be taken into consideration. The aim of this report was to present data on the epidemiology of olfactory dysfunction during the pandemic and compare this dataset with a pre-pandemic set. We hypothesized an increase in URTI-related olfactory dysfunction. METHODS: Data of paediatric patients consulting a smell and taste clinic between March 2020 and June 2022 were retrospectively analysed. The frequency of major causes of olfactory dysfunction was examined and compared with three subsets of an older dataset. RESULTS: A total of 52 patients were included in the analysis. Most children presented with olfactory dysfunction due to upper respiratory tract infection (URTI) (52%). Congenital olfactory dysfunction was present in 34% of cases. Sinonasal disorders and idiopathic cases accounted for 6 and 4%, respectively, whereas head trauma was the least common cause (2%). This was in contrast with the results of the older set. The frequency of URTI-related olfactory dysfunction increased significantly. The frequency of head-trauma-related or congenital olfactory dysfunction showed marked reductions. There were no significant differences regarding the other aetiologies between our patient cohort and the three subsets. CONCLUSION: The COVID-19 pandemic has resulted in differences regarding the prevalence of aetiologies between our dataset and the subsets of pre-pandemic times. The surge of the frequency of URTI-related olfactory dysfunction may be ascribed to a novel pathomechanism involving sustentacular cells in the olfactory epithelium.

Long-term smell loss experiences after COVID-19: A qualitative study.

OBJECTIVES: Sudden smell loss is one of the early symptoms of COVID-19. Although it is stated that the loss of smell and taste following COVID-19 improves within a few weeks, there are also cases that do not improve for a long time. The aim of this study is to reveal long-term smell loss experiences after COVID-19. METHODS: A qualitative approach was adopted. We conducted semistructured interviews with 11 participants who had smell loss for at least 3 months. Interviews were recorded, transcribed and evaluated using a thematic analysis for qualitative data. RESULTS: Nutrition and appetite, personal hygiene, threats to safety and emotional changes were the main themes created by the authors and were the areas where participant expressions focused. The participants used oral/nasal corticosteroid therapy for smell loss and received short-term olfactory training, but could not find a solution. CONCLUSIONS: Long-term smell loss problems, which were neglected during the pandemic period, should be carefully evaluated due to their negative effects. Understanding and focusing on the negative effects of loss of smell may contribute to the solution of long-term smell loss problems. PATIENT AND PUBLIC CONTRIBUTION: Eleven participants who experienced long-term loss of smell following COVID-19 contributed to the study. They enriched the study by describing the effects of their experiences. There was no other participation or contribution from the public to the research.

Platelet-Rich Plasma for Patients with Olfactory Dysfunction: Myth or Reality? A Systematic Review.

BACKGROUND: With promising outcomes, platelet-rich plasma (PRP) has recently been suggested as a treatment for olfactory dysfunction (OD). METHODS: Clinical studies utilizing PRP in OD caused by COVID-19, trauma, anesthetic exposure, viral infection, and chronic rhinosinusitis were included in a systematic review. RESULTS: Ten clinical studies were qualitatively analyzed. Six of these studies used the PRP for OD caused by COVID-19, one on OD after functional endoscopic sinus surgery, and three on post-infectious or post-trauma OD. The population included 531 patients, ranging in age from 15 to 63. CONCLUSION: The use of PRP may be a risk-free and efficient therapeutic option with very encouraging outcomes. Indeed, it enhances olfactory perception in patients who not only exhibit COVID-19 infection aftereffects, but also in those who have lost their sense of smell due to trauma, rhinosinusitis, rhinitis, or even surgery. To evaluate the PRP's therapeutic benefits in OD patients and to compare the efficacy of different therapeutic protocols with regard to treatment schedules, there is an urgent need for focused controlled trials.

Mechanisms of COVID-19-associated olfactory dysfunction.

Olfactory dysfunction is one of the most common symptoms of COVID-19. In the first 2 years of the pandemic, it was frequently reported, although its incidence has significantly decreased with the emergence of the Omicron variant, which has since become the dominant viral strain. Nevertheless, many patients continue to suffer from persistent dysosmia and dysgeusia, making COVID-19-associated olfactory dysfunction an ongoing health concern. The proposed pathogenic mechanisms of COVID-19-associated olfactory dysfunction are complex and likely multifactorial. While evidence suggests that infection of sustentacular cells and associated mucosal inflammation may be the culprit of acute, transient smell loss, alterations in other components of the olfactory system (e.g., olfactory receptor neuron dysfunction, olfactory bulb injury and alterations in the olfactory cortex) may lead to persistent, long-term olfactory dysfunction. This review aims to provide a comprehensive summary of the epidemiology, clinical manifestations and current understanding of the pathogenic mechanisms of COVID-19-associated olfactory dysfunction.

Pro-inflammatory markers associated with COVID-19-related persistent olfactory dysfunction.

INTRODUCTION: While localized inflammation has been implicated in the pathophysiology of acute coronavirus disease of 2019 (COVID-19) olfactory dysfunction (OD), persistent COVID-19 OD remains poorly understood with limited therapeutics. Our prospective study evaluated olfactory cleft (OC) biomarkers as predictors of persistent OD in mucus sampling. METHODS: COVID-19 subjects with persistent OD >3 months confirmed by psychophysical olfaction tests were compared to COVID-19 subjects with no OD and those with no prior infection. OC mucus samples were evaluated for 13 anti-viral and inflammatory biomarkers. Cohorts were compared using analysis of variance (ANOVA) and Mann-Whitney tests with multi-comparison adjustment. Viral RNA was assessed through RT-PCR using the COVID-19 N2 primer. RESULTS: Thirty-five samples were collected (20 COVID persistent OD, 8 COVID no OD, and 7 non-COVID no OD). Significant differences in IFN-λ1 (p = 0.007) and IFN-γ (p = 0.006) expression in OC mucus were found across all three groups, with the highest cytokine concentrations corresponding to COVID OD. IFN-α2 levels were elevated in COVID OD versus no OD (p = 0.026). Mean IFN-γ levels were the highest in COVID OD, but there were higher levels found in COVID no OD compared to non-COVID no OD (p = 0.008). No difference was seen in IL6. No N2 gene expression was detected in all cohorts. CONCLUSION: IFN pathway cytokines were found elevated in the olfactory microenvironment of COVID-19 persistent OD compared to those with no OD and no prior history of COVID-19 infection.

Identifying candidate genes underlying isolated congenital anosmia.

An estimated 1 in 10 000 people are born without the ability to smell, a condition known as congenital anosmia, and about one third of those people have non-syndromic, or isolated congenital anosmia (ICA). Despite the significant impact of olfaction for our quality of life, the underlying causes of ICA remain largely unknown. Using whole exome sequencing (WES) in 10 families and 141 individuals with ICA, we identified a candidate list of 162 rare, segregating, deleterious variants in 158 genes. We confirmed the involvement of CNGA2, a previously implicated ICA gene that is an essential component of the olfactory transduction pathway. Furthermore, we found a loss-of-function variant in SREK1IP1 from the family gene candidate list, which was also observed in 5% of individuals in an additional non-family cohort with ICA. Although SREK1IP1 has not been previously associated with olfaction, its role in zinc ion binding suggests a potential influence on olfactory signaling. This study provides a more comprehensive understanding of the spectrum of genetic alterations and their etiology in ICA patients, which may improve the diagnosis, prognosis, and treatment of this disorder and lead to better understanding of the mechanisms governing basic olfactory function.

Understanding olfactory dysfunction in the COVID-19 era: insights from a cross-sectional survey of the Saudi community.

Background and objectives: COVID-19 has emerged as a public health emergency caused by the coronavirus 2 (SARS-CoV2). However, only a few studies have reported that anosmia is an early predictor of COVID-19. Therefore, this study aimed to assess the current level of knowledge regarding smell dysfunction in COVID-19 era in Saudi community. Materials and methods: An online survey was conducted using Survey Monkeys in Saudi Arabia. The survey was distributed through Twitter and WhatsApp. The questionnaire included individuals' demographic information, such as sex, age, residence, income, and qualifications, as well as their knowledge of the early symptoms of COVID-19. ANOVA and Mann-Whitney U-test were conducted to analyze the data. There were twelve items on knowledge dimensions which were assessed through five-point Likert scale. Results: In total, 809 respondents completed the questionnaire. Among them, 658 (81.3%) had no knowledge of how sudden loss of or change in the sense of smell can be the only symptom of COVID-19. However, most participants, 738 (91.2%), knew that fever was a symptom of COVID-19. Similarly, 707 (87.4%) and 772 (95.5%) participants knew that cough and shortness of breath were the major symptoms of COVID-19, respectively. In addition, 395 (48.3%) participants had no information regarding taste changes as a symptom of COVID-19. Notably, participants who were female, married, or diagnosed with COVID-19 had significantly greater knowledge of smell-related issues due to COVID-19 than males, unmarried, and healthy/those without COVID-19. Conclusion: This study revealed that the Saudi population has an fairly good level of knowledge regarding common COVID-19 symptoms as more than 90% of the participants understood symptoms of COVID-19, but less acceptable knowledge regarding smell and taste dysfunction as more than 80% had no knowledge of change in olfactory and taste function was due to COVID-19.

Prevalence and Prognostic Factors Associated with Early Recovery of Olfactory Dysfunction in COVID-19 Patients.

BACKGROUND: The prevalence of smell dysfunction, along with its risk factors, has been evaluated in previous literature; however, little has been established regarding its relation to other factors such as disease severity, history of coronavirus disease-2019 (COVID-19) vaccinations, and medical treatment for COVID-19 infection. These factors may impact the overall recovery of olfaction in COVID-19 patients. OBJECTIVE: This study investigated the prevalence of early olfactory recovery from COVID-19 infection and its associated factors. METHODS: This study was a prospective cohort study on 348 COVID-19 patients with a new onset of anosmia or hyposmia. Smell sensation scores on the olfactory self-assessment test were collected at baseline and every week until 6 weeks of follow-up. The primary outcome was the prevalence of early olfactory recovery. The secondary outcomes were analyzing factors associated with early olfactory recovery and the median time to complete recovery of smell loss. RESULTS: The prevalence of early olfactory recovery was 63.1% (95% CI: 0.58-0.68), and significant associated factors in multivariate analysis included patients without allergic rhinitis (OR 2.22, 95% CI: 1.12-4.40, P = 0.023) and no alteration of taste perception (OR 1.62, 95% CI: 1.02-2.57, P = 0.042). The median time to complete recovery from smell loss was 2 weeks. CONCLUSION: The present study found that the prevalence of early olfactory recovery within 2 weeks was 63.1%. The median time to olfactory recovery was also 2 weeks. Patients without allergic rhinitis and taste alteration had a significantly better chance of early recovery of olfactory function.

Characteristics of olfactory dysfunction in patients with long-haul covid-19.

Background: A subset of individuals suffering from Coronavirus Disease 2019 (COVID-19) will experience ongoing symptoms that last longer than three months (i.e., long-haul COVID). This includes olfactory dysfunction (OD), which is currently estimated to occur in 1-63.5% of patients at one-year post-infection. However, OD in individuals with long-haul COVID-19 is poorly understood, and there is little information regarding how initial SARS-CoV-2 variants correlate with long-haul symptoms. In this study, we investigated the prevalence and severity of OD in patients with long-haul COVID-19 and investigated how OD severity varied with SARS-CoV-2 variants. Methods: Patients were recruited from the University of North Carolina-Chapel Hill COVID Recovery Clinic. Each patient completed the University of Pennsylvania Smell Identification Test (UPSIT). The dominant strain at the time of infection was determined using the date of COVID-19 diagnosis, and Centers for Disease Control and Prevention, World Health Organization, and North Carolina Department of Health and Human Services databases. Results: Nearly 85% of patients with long-haul COVID-19 reported some degree of OD, which persisted in some patients for two or more years from the date of the initial infection. There was no association between the time since COVID-19 infection and severity of OD. No difference was detected between OD in patients with long-haul COVID-19 based on the dominant variant at the time of infection (p=0.0959). Conclusion: A vast majority of patients with long-haul COVID-19 had some degree of ongoing olfactory complications, although the severity of symptoms was not dependent on the dominant SARS-CoV-2 variant at the time of infection.

Development and Validation of the Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR).

OBJECTIVE: Develop and validate a quality-of-life (QoL) outcome measure for patients with dysosmia. STUDY DESIGN: Cross-sectional survey study. SETTING: Otolaryngology clinics, research registries, and Facebook support groups. METHODS: A 59-item pilot survey with questions addressing parosmia concerns was developed using input from subjects with parosmia and clinical expertise from Otolaryngologists. After item reduction, the Parosmia Olfactory Dysfunction Outcomes Rating (DisODOR) was reduced to its final 29 items. DisODOR maximum score is 116 (each item score 0-4) with higher scores indicating a higher degree of dysfunction from smell distortion. DisODOR was validated using participants with parosmia persisting >3 months after severe acute respiratory syndrome coronavirus 2 (cases) and healthy controls. Reliability, face and content validity, internal consistency, convergent validity, discriminative validity, sensitivity to change, and the minimal clinically important difference (MCID) were assessed. RESULTS: A total of 134 cases and 20 controls completed DisODOR. The mean (SD) age was 45.9 (12.2) for cases and 29.6 (8.9) for controls. The mean score difference between cases and controls was 45.0 (95% confidence interval, 40.5-49.5) displaying good discriminative validity. DisODOR showed strong test-retest reliability (r = .942) with high internal consistency (Cronbach's α = .971). DisODOR had a moderate correlation with SNOT-22 scores (r = .619) indicating good convergent validity. There is an excellent association with the global impression of severity categories (η2 = 0.447). Based on the distribution method, the MCID is 15. CONCLUSION: DisODOR is a valid, reliable QoL instrument for parosmia that can be used to measure the functional impact and QoL impairment for parosmia patients. DisODOR is sensitive to change and thus can be used in studies investigating treatments for parosmia.

A Pilot Study of Short-Course Oral Vitamin A and Aerosolised Diffuser Olfactory Training for the Treatment of Smell Loss in Long COVID.

Background: Olfactory dysfunction (OD) is a common neurosensory manifestation in long COVID. An effective and safe treatment against COVID-19-related OD is needed. Methods: This pilot trial recruited long COVID patients with persistent OD. Participants were randomly assigned to receive short-course (14 days) oral vitamin A (VitA; 25,000 IU per day) and aerosolised diffuser olfactory training (OT) thrice daily (combination), OT alone (standard care), or observation (control) for 4 weeks. The primary outcome was differences in olfactory function by butanol threshold tests (BTT) between baseline and end-of-treatment. Secondary outcomes included smell identification tests (SIT), structural MRI brain, and serial seed-based functional connectivity (FC) analyses in the olfactory cortical network by resting-state functional MRI (rs-fMRI). Results: A total of 24 participants were randomly assigned to receive either combination treatment (n = 10), standard care (n = 9), or control (n = 5). Median OD duration was 157 days (IQR 127-175). Mean baseline BTT score was 2.3 (SD 1.1). At end-of-treatment, mean BTT scores were significantly higher for the combination group than control (p < 0.001, MD = 4.4, 95% CI 1.7 to 7.2) and standard care (p = 0.009) groups. Interval SIT scores increased significantly (p = 0.009) in the combination group. rs-fMRI showed significantly higher FC in the combination group when compared to other groups. At end-of-treatment, positive correlations were found in the increased FC at left inferior frontal gyrus and clinically significant improvements in measured BTT (r = 0.858, p < 0.001) and SIT (r = 0.548, p = 0.042) scores for the combination group. Conclusions: Short-course oral VitA and aerosolised diffuser OT was effective as a combination treatment for persistent OD in long COVID.

Smell and Taste Loss Associated with COVID-19 Infection.

OBJECTIVE: The aim of this study was to quantify the impact of COVID-19 on olfactory and gustatory function in US adults. METHODS: From the 2021 Adult National Health Interview Survey, demographic and survey-specific module data concerning COVID-19 diagnoses, testing and disease severity, and data quantifying disturbances and eventual recovery of smell and taste were extracted. Sample weights were applied to obtain nationally representative statistics. The overall rate of COVID-19 infection was determined, and those diagnosed with COVID-19 were analyzed with respect to disease severity, smell and taste disturbance, and respective recoveries. RESULTS: In 2021, 35.8 million or 14% of the adult population (95% CI 13.5-14.7%; mean age, 43.9 years; 53.8% female) had been diagnosed with COVID-19. Among those, 60.5% (58.6-62.5%) and 58.2% (56.2-60.1%) reported accompanying losses  in smell or taste, respectively; there was a significant association between overall COVID-19 symptom severity and smell (p < 0.001) and taste disturbance (p < 0.001). Following infection, 72.2% (69.9-74.3%), 24.1% (22.2-26.2%), and 3.7% (3.0-4.6%) of the patients experienced complete, partial, and no smell recovery, respectively. Recovery rates for gustatory function paralleled olfaction, with 76.8% (74.6-78.9%), 20.6% (18.7-22.7%), and 2.6 (1.9-3.4%) reporting complete, partial, and no recovery of taste, respectively. When sensory disturbance was present, severity of overall symptomatology was negatively associated with smell and taste recovery (p < 0.001 for each). CONCLUSION: The majority of adults infected with COVID-19 in 2021 experienced olfactory or gustatory dysfunction with a non-negligible population reporting incomplete or no near-term sensory recovery. Our results are useful for providers counseling patients and suggest that interventions lessening overall COVID-19 symptom burden may prevent prolonged sensory dysfunction. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2357-2361, 2023.

COVID-19-Associated Chemosensory Loss Continues to Decline.

Chemosensory losses have long been considered a cardinal symptom of COVID-19 infection. Recent studies have shown changing symptom profiles with COVID-19, including decreasing incidence of olfactory losses. We accessed the National COVID Cohort Collaborative database to identify patients with and without smell and taste loss within 2 weeks of COVID-19 diagnosis. Peak prevalence time intervals for variants were determined from Covariants.org. Using rates of chemosensory loss during the peak time interval for "Untyped" variants as baseline (4/27/2020-6/18/2020), odds ratios for COVID-19-associated smell or taste disturbance fell for each of the Alpha (0.744), Delta (0.637), Omicron K (0.139), Omicron L (0.079), Omicron C (0.061), and Omicron B (0.070) peak intervals. These data suggest that during the recent Omicron waves and potentially moving forward, the presence or absence of smell and taste disturbances may no longer have predictive value in the diagnosis of COVID-19 infection.

Parosmia COVID-19 Related Treated by a Combination of Olfactory Training and Ultramicronized PEA-LUT: A Prospective Randomized Controlled Trial.

During COVID-19 pandemic, clinicians have had to deal with an ever-increasing number of cases of olfactory disturbances after SARS-CoV-2 infections and in some people this problem persisted for long time after negativization from virus. This a prospective randomized controlled trial aims at evaluating the efficacy of ultramicronized palmitoylethanolamide (PEA) and Luteolin (LUT) (umPEA-LUT) and olfactory training (OT) compared to OT alone for the treatment of smell disorders in Italian post-COVID population. We included patients with smell loss and parosmia who were randomized and assigned to Group 1 (intervention group; daily treatment with umPEA-LUT oral supplement and OT) or Group 2 (control group; daily treatment with placebo and OT). All subjects were treated for 90 consecutive days. The Sniffin' Sticks identification test was used to assess the olfactory functions at the baseline (T0) and the end of the treatment (T1). Patients were queried regarding any perception of altered olfaction (parosmia) or aversive smell, such as cacosmia, gasoline-type smell, or otherwise at the same observational points. This study confirmed the efficacy of combination of umPEA-LUT and olfactory training as treatment of quantitative smell alteration COVID-19 related, but the efficacy of the supplement for parosmia was limited. UmpEA-LUT is useful for the treatment of brain neuro-inflammation (origin of quantity smell disorders) but has limited/no effect on peripheral damage (olfactory nerve, neuro-epithelium) that is responsible of quality disorders.

Viral Shedding and Persistence of Anosmia and Ageusia in an Asymptomatic SARS-CoV-2 Infection.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first identified in the region of Wuhan, China is responsible for the ongoing pandemic of coronavirus disease-19 (COVID-19) that has been a part of our life for almost three years now. Although there have been multiple reports of prolonged viral shedding in people with severe disease, viral shedding lasting for extended periods can occur in patients with less serious clinical insults or even asymptomatic individuals. Herein, we report a case of a female patient that, although otherwise asymptomatic, remained positive on nasopharyngeal viral testing for a prolonged period, alongside persisting complaints of anosmia and ageusia. The patient may well have been one of the first individuals to be infected in the Greek territory; we followed up on her long-term COVID sequelae from the time of proof of infection up until the present day.

Use of platelet-rich plasma for COVID-19-related olfactory loss: a randomized controlled trial.

INTRODUCTION: The current study evaluated the use of platelet-rich plasma (PRP), an autologous blood product with supraphysiologic concentrations of growth factors, in the treatment of prolonged coronavirus disease 2019 (COVID-19)-related smell loss. METHODS: This multi-institutional, randomized controlled trial recruited patients with COVID-19 who had objectively measured smell loss (University of Pennsylvania Smell Identification Test [UPSIT] ≤ 33) between 6 and 12 months. Patients were randomized to three intranasal injections of either PRP or sterile saline into their olfactory clefts. The primary outcome measure was change in Sniffin' Sticks score (threshold, discrimination, and identification [TDI]) from baseline. The secondary end point measures included responder rate (achievement of a clinically significant improvement, ≥5.5 points TDI), change in individual TDI olfaction scores, and change in subjective olfaction via a visual analog scale. RESULTS: A total of 35 patients were recruited and 26 completed the study. PRP treatment resulted in a 3.67-point (95% CI: 0.05-7.29, p = 0.047) greater improvement in olfaction compared with the placebo group at 3 months and a higher response rate (57.1% vs 8.3%, odds ratio 12.5 [95% exact bootstrap confidence interval, 2.2-116.7]). There was a greater improvement in smell discrimination following PRP treatment compared with placebo but no difference in smell identification or threshold. There was no difference in subjective scores between PRP and placebo. No adverse effects were reported. CONCLUSION: Olfactory function following COVID-19 can improve spontaneously after 6 months and can improve to a greater extent with PRP injection. These data build on the promise of PRP to be a safe potential treatment option for patients with COVID-19-related smell loss, and larger-powered studies will help further assess its efficacy.