The Molecular Basis of Olfactory Dysfunction in COVID-19 and Long COVID.

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

SARS-CoV-2 and Other Respiratory Viruses in Human Olfactory Pathophysiology.

Acute respiratory viruses (ARVs) are the leading cause of diseases in humans worldwide. High-risk individuals, including children and the elderly, could potentially develop severe illnesses that could result in hospitalization or death in the worst case. The most common ARVs are the Human respiratory syncytial virus, Human Metapneumovirus, Human Parainfluenza Virus, rhinovirus, coronaviruses (including SARS and MERS CoV), adenoviruses, Human Bocavirus, enterovirus (-D68 and 71), and influenza viruses. The olfactory deficits due to ARV infection are a common symptom among patients. This review provides an overview of the role of SARS-CoV-2 and other common ARVs in the development of human olfactory pathophysiology. We highlight the critical need to understand the signaling underlying the olfactory dysfunction and the development of therapeutics for this wide-ranging category of AVRs to restore the altered or loss of smell in affected patients.

Neurological Manifestation in Hospitalized Patients With Acute SARS-CoV-2 Infection.

OBJECTIVE: The main objective of this research is to determine the prevalence and characteristics of neurological manifestations in hospitalized patients with SARS-CoV-2 infection. METHODS: A cross-sectional study was conducted. 572 hospitalized patients at the COVID Department of Pulmonology of the Mostar University Clinical Hospital in the six-month period from October 31, 2020, to April 30, 2021, were included. We analyzed the incidence of neurological manifestations and the influence of comorbidities and metabolic syndrome on stroke incidence in COVID-19 patients. We analyzed hospital length of stay and mortality in patients with and without neurological manifestations. The research was conducted with respect to all the determinants of the Helsinki Declaration. RESULTS: 572 patients, 351 men (61.4%), and 221 women (38.6%) were included. A fatal outcome was present in a quarter of patients (25.3%). Neurological manifestations were found in 163 patients (28.5%). Myalgia was the most common (16.1%). The following were reported: headache (9.6%), loss of taste (7.34%), loss of smell (6.8%), and vertigo (2.5%). There was a significant difference regarding loss of smell between males and females (p=0.04). The cerebrovascular incident was present in 2.97% of patients and was more frequent in the group of patients with metabolic syndrome. Patients with neurological manifestations had a longer hospital stay, but it was not statistically significant (p=0.9319). The presence of neurological manifestations in general did not influence the mortality rate. CONCLUSION: Patients with SARS-CoV-2 infection can present with neurologic findings such as myalgia, headache, loss of smell or taste, vertigo, as well as cerebrovascular incidents. Patients with neurological manifestations had longer hospital stays, but the presence of neurological manifestations in general did not influence the mortality rate.

Bidirectional relationship between olfaction and Parkinson's disease.

Background: Hyposmia (loss of smell) is a common early symptom of Parkinson's disease (PD). The shared genetic architecture between hyposmia and PD is unknown. Methods: We leveraged genome-wide association study (GWAS) results for self-assessment of 'ability to smell' and PD diagnosis. Linkage disequilibrium score regression (LDSC) and Local Analysis of [co]Variant Association (LAVA) were used to identify genome-wide and local genetic correlations. Mendelian randomization was used to identify potential causal relationships. Results: LDSC found that sense of smell negatively correlated at a genome-wide level with PD. LAVA found negative correlations in four genetic loci near GBA1, ANAPC4, SNCA, and MAPT. Using Mendelian randomization we found evidence for strong causal relationship between PD and liability towards poorer sense of smell, but weaker evidence for the reverse direction. Conclusions: Hyposmia and PD share genetic liability in only a subset of the major PD risk genes. While there was definitive evidence that PD can lower the sense of smell, there was only suggestive evidence for the reverse. This work highlights the heritability of olfactory function and its relationship with PD heritability and provides further insight into the association between PD and hyposmia.

Efficacy of Stellate Ganglion Block in Treating Long-Term COVID-19-Related Olfactory and Gustatory Dysfunction: A Case Series.

Olfactory and gustatory dysfunction, including anosmia, parosmia, ageusia, and dysgeusia, are common long-term symptoms of coronavirus disease 2019 (COVID-19) infection. These symptoms can have a severe impact on quality of life of a patient, including psychological well-being. Stellate ganglion block (SGB) has recently been explored as a potential therapeutic intervention for these symptoms. In this case series, we present six patients with long-term COVID-19 symptoms and we detail how their symptoms evolved after an SGB. All SGB were performed under ultrasound guidance by the same physician. Patients had a right SGB during the initial visit, followed by a left SGB at a subsequent visit. All but one patient reported improvements in olfaction and gustation after the SGB. Our findings suggest that SGB may be a promising therapeutic intervention for patients with olfactory and gustatory dysfunction related to long-term COVID-19 symptoms. Further research is needed to confirm these findings and to explore the optimal treatment protocol.

Olfactory and Gustatory Dysfunctions Following COVID-19 Infection: Factors That Affect Their Duration in Saudi Arabia.

INTRODUCTION:  Many people infected with coronavirus disease 2019 (COVID-19) have developed post-COVID-19 symptoms, which are defined as symptoms and signs (e.g., anosmia and ageusia) that persist for more than 12 weeks after getting infected with COVID-19. These symptoms may appear after or during the infection and cannot be explained by any alternative disease. In this study, we aim to investigate the factors that affect the duration of anosmia and ageusia in Saudi Arabia. METHODS:  We conducted a nationwide, cross-sectional study using an online survey in Saudi Arabia from 14 February 2022 to 23 July 2022. The electronic survey was distributed using social media platforms, such as Twitter, WhatsApp, and Telegram. RESULT:  The study enrolled 2497 individuals who were infected with COVID-19. A total of 60.1% of the participants showed symptoms of anosmia, ageusia, or both after getting infected with COVID-19. According to our data, we found that being a female and not having a repeated COVID-19 infection were risk factors (independent predictors) of the long duration of anosmia after COVID-19 recovery (p = <0.05). While being a male patient, a smoker, and being admitted to the ICU were risk factors (independent predictors) of long duration of ageusia after COVID-19 recovery (p = <0.05). CONCLUSION:  In conclusion, the prevalence of chemosensory dysfunction symptoms, both olfactory and gustatory, after COVID-19 infection among the Saudi population was high. However, several factors can influence their duration, including gender, smoking, and severity of the infection.

Visual Analog Scale and Olfactory Objective Tests in Hyposmia Patients: Is There a Link?

Introduction Olfactory dysfunction (OD) is often a devaluated sensorial affection. The objective evaluation of this dysfunction does not evaluate its compromise in patients' daily life. It is unclear to what extent there is a correlation between the objective evaluation of OD and patient-reported impairment. Objective We aim to search if Sniffin Sticks® correlates with the Visual Analog Scale (VAS) of Hyposmia Symptoms, and therefore if it is a useful method for clinical use. Methods A prospective study was carried out to evaluate and compare consecutive patients who had olfactory impairment due to COVID-19 that were referred to an otolaryngology office. The variables evaluated were gender, age, co-morbidities, and olfactory thresholds (measured according to Sniffin Sticks®). Patients were also enquired about their sense of impairment according to VAS from 1 (worst possible) to 10 (best possible). Statistical analysis was performed using SPSS (IBM SPSS Statistics 26). Normal distribution was checked using both skewness and kurtosis and Kolmogorov-Smirnov tests. Pearson correlation test was used to seek a correlation between VAS and olfactory thresholds. All reported p-values are two-tailed, with a p-value ≤ 0.05 indicating statistical significance. Results Our sample of 47 patients was composed of 30 females (63.8%) and 17 females (36.2%). We found a mean variation between olfactory thresholds before and after the intervention of 3.91±2.466, and an average improvement of 2.29±2.93 in the visual analog scale for subjective evaluation of olfactory impairment. According to the Pearson correlation test, with 95% confidence, there is evidence to claim a moderate association (0.512) between an improvement in olfactory thresholds and VAS (p=0.05). Conclusions There was a moderate correlation between ratings and measures of olfactory function. On an individual basis, there were remarkable differences between measures and ratings of olfactory function. VAS should be considered in the evaluation of the hyposmic patient, due to its simplicity and quick applicability.

Treatment of Olfactory Disorders After SARS - CoViD 2 Virus Infection.

OBJECTIVE: The benefit of a nasal corticosteroid in the treatment of persistent post-infectious smell disorders is not as clear in previous studies as is assumed for olfactory training. This study would therefore like to describe the treatment strategies using the example of a persistent olfactory dysfunction as a result of a proven infection with SARS-CoViD-2-virus. METHODS: Twenty patients (average age of 33.9 ± 11.9 years) with hyposmia were included in this study from December 2020 to July 2021. Every second patient received additionally a nasal corticosteroid. The two resulting randomized groups of equal size were screened with the TDI test, a 20-item taste powder test for the assessment of retronasal olfaction and otorhinolaryngological examination. The patients were asked to train twice daily using a standardized odor training kit and followed up after 2 months and 3 months, respectively. RESULTS: We documented a significant overall improvement in olfactory ability over the investigation period in both groups. While the TDI score steadily increased on average under the combination therapy, the rise under olfactory training alone was initially steeper. This short-term interaction effect over mean two months was not statistically significant. According to Cohen, however, a moderate effect (eta2 = 0.055, Cohen`s d = 0.5) can still be assumed. This effect could be explained by a possibly higher compliance at the beginning of the sole olfactory training due to the lack of further drug treatment offers. When the training intensity decreases, the recovery of the sense of smell stagnates. Adjunctive therapy ultimately outweighs this short-term benefit. CONCLUSIONS: The results reinforce the recommendation of early and consistent olfactory training on patients with dysosmia due to COVID-19. For continuous improvement of the sense of smell, an accompanying topical treatment seems at least to be worth consideration. The results should be optimized with larger cohorts and using new objective olfactometric methods.

Doxycycline Improves Quality of Life and Anosmia in Chronic Rhinosinusitis With Nasal Polyposis: A Randomized Controlled Trial.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex disorder and effective treatment remains a major challenge. Some antibiotics with anti-inflammatory properties are reported to have potential to be used as an adjunct therapy in the management of chronic airway inflammation. OBJECTIVE: The aim of this study was to evaluate the efficacy of doxycycline in CRSwNP. METHODS: In this randomized, double-blind, placebo-control study, we assessed the efficacy of doxycycline in patients with moderate to severe CRSwNP. A total of 100 patients were randomly assigned to receive either doxycycline (200 mg on the first day followed by 100 mg daily) or placebo for 6 weeks. All patients received baseline therapy with fluticasone, montelukast, and nasal irrigation during the study. The primary outcome was quality of life based on the sino-nasal outcome test (SNOT-22) questionnaire. We measured peak nasal inspiratory flow (PNIF) and severity of symptoms by visual analogue scale (VAS). Baseline blood eosinophil count, serum IgE level, eosinophil in nasal secretions, and Lund-Mackay score based on low dose paranasal CT scan were also recorded. RESULTS: Treatment with doxycycline significantly improved SNOT-22 (P = .037) and sense of smell (P = .048). The baseline SNOT-22 score had no effect on outcomes. The effect of doxycycline on quality of life in patients with or without nasal eosinophilia was not significantly different. Change in SNOT-22 score was also not correlated with serum IgE (P = .220, r = -0.186) and the eosinophil count (P = .190, r = -0.198). CONCLUSION: Doxycycline improves the quality of life in patients with CRSwNP. It also has temporarily beneficial effects in improving the sense of smell. The levels of eosinophil in the blood and nasal secretions do not affect the response to treatment. Hence, doxycycline can be used in both eosinophilic and non-eosinophilic nasal polyps.This study was registered at Iranian Registry of Clinical Trials. https://www.irct.ir/ IRCTID: IRCT20210403050817N1.

Prevalence of Olfactory Dysfunction with the Omicron Variant of SARS-CoV-2: A Systematic Review and Meta-Analysis.

The omicron variant is thought to cause less olfactory dysfunction than previous variants of SARS-CoV-2, but the reported prevalence differs greatly between populations and studies. Our systematic review and meta-analysis provide information regarding regional differences in prevalence as well as an estimate of the global prevalence of olfactory dysfunction based on 62 studies reporting information on 626,035 patients infected with the omicron variant. Our estimate of the omicron-induced prevalence of olfactory dysfunction in populations of European ancestry is 11.7%, while it is significantly lower in all other populations, ranging between 1.9% and 4.9%. When ethnic differences and population sizes are considered, the global prevalence of omicron-induced olfactory dysfunction in adults is estimated to be 3.7%. Omicron's effect on olfaction is twofold to tenfold lower than that of the alpha or delta variants according to previous meta-analyses and our analysis of studies that directly compared the prevalence of olfactory dysfunction between omicron and previous variants. The profile of the prevalence differences between ethnicities mirrors the results of a recent genome-wide association study that connected a gene locus encoding an odorant-metabolizing enzyme, UDP glycosyltransferase, to the extent of COVID-19-related loss of smell. Our analysis is consistent with the hypothesis that this enzyme contributes to the observed population differences.

Effects of classical olfactory training in patients with COVID-19-related persistent loss of smell.

PURPOSE: The management of post-COVID-19 persistent olfactory dysfunction (OD) is uncertain. Currently, olfactory training is the only evidence-based therapy for post-viral OD. In this study, we evaluated the effectiveness of classical olfactory training (COT) in the treatment of post-COVID-19 persistent OD. MATERIALS AND METHODS: Patients with persistent OD after COVID-19 were assessed using the Sniffin' Sticks test. Fifty-one patients were then divided into two groups based on personal preference: the COT group (n = 31) included subjects who performed COT over 12 weeks, and the control group (n = 20) included subjects who did not receive any treatment. After the exclusion of eight patients, the olfactory performances of 43 patients were re-evaluated and compared to the baseline values. RESULTS: A significantly higher proportion of patients in the COT group improved their olfactory scores above the clinically important difference compared to the control group (40% versus 6%) (p = 0.014). The subjective smell improvement by COT was independent of age, gender, OD duration, presence of parosmia, or the initial olfactory score (all p > 0.05). CONCLUSION: Twelve weeks of COT appears to increase the olfactory sensitivity in patients with persistent OD following COVID-19.

COVID-19 loss of taste and smell: potential psychological repercussions.

The novel coronavirus (COVID-19) has become a cause for global concern. Apart from a multitude of symptoms, the virus is known for its ability to cause loss of taste and smell that can be irreversible in a few cases. In fact, even after recovery, post-covid syndrome can still lead to devastating outcomes, specifically with reference to loss of smell and taste. A number of mechanisms that have been postulated include receptor-mediated uptake, increased inflammation, transneuronal migration, and direct damage to the olfactory pathway. Considering how important these two senses are, many psychological, social, and emotional repercussions can be expected. These repercussions include lowering of self-esteem and developmental of mental health issues. Long-term altered taste sensation can also lead to the development of unhealthy eating habits that can result in increasing risk for diabetes and hypertension. A few solutions have been investigated for treating these chemosensory dysfunctions, such as olfactory training, corticosteroids, theophylline and acupuncture. Although the results have been promising but a new modality, virtual reality, requires more in-depth exploration because it targets not only the dysfunction but also the mental health issues being experienced. It is important that affected individuals be provided with strong emotional and family support. Additionally, physicians can help the patients through support groups, cognitive behavioural therapy, olfactory, and virtual reality training.

Management of Anosmia in COVID-19: A Comprehensive Review.

With the evolving understanding of COVID-19, a thorough analysis of the effects of this unique coronavirus on the affected people's olfactory abilities could highlight the disease's specific course of treatment. Researchers have discovered that the neurological side effects of SARS-CoV-2 infection include acute anosmia and ageusia. This work aims to review the relevant mechanisms, provide information on COVID-19-related anosmia, and suggest a novel approach to treating long-term anosmia brought on by coronavirus disease. For that, we did a thorough literature assessment of the subject from various online resources, including PubMed, Scopus, and Google Scholar. We evaluated the publications that described anosmia in COVID-19 and its management. In patients with SARS-CoV-2 infections, the angiotensin-converting enzyme two receptor plays a crucial role in the anosmia process. Olfactory systems are directly harmed by new coronaviruses when they connect with sustentacular cells' ACE-2 (Angiotensin converting enzyme-2) receptors. Other suggested processes include the virus's infiltration of the olfactory nerve and the ensuing local inflammation. Therefore, neuroprotective, anti-inflammatory, or depolarizing medications may be helpful for COVID-19 individuals who have lost their sense of smell. According to the available data, we found out olfactory training, topical or oral corticosteroids, caffeine, insulin, or minocycline may effectively treat COVID-19 odor loss. A novel method of treating long-term COVID-19 with persistent anosmia can be suggested based on recent investigations. The path to effective anosmia management is still somewhat hazy, but there is hope that we can find the right treatment plan with the right clinical trials and additional research. People who lost their sense of smell during COVID-19 can be reassured that recovery is typically possible.

Discovery and Analytical Validation of a Vocal Biomarker to Monitor Anosmia and Ageusia in Patients With COVID-19: Cross-sectional Study.

BACKGROUND: The COVID-19 disease has multiple symptoms, with anosmia and ageusia being the most prevalent, varying from 75% to 95% and from 50% to 80% of infected patients, respectively. An automatic assessment tool for these symptoms will help monitor the disease in a fast and noninvasive manner. OBJECTIVE: We hypothesized that people with COVID-19 experiencing anosmia and ageusia had different voice features than those without such symptoms. Our objective was to develop an artificial intelligence pipeline to identify and internally validate a vocal biomarker of these symptoms for remotely monitoring them. METHODS: This study used population-based data. Participants were assessed daily through a web-based questionnaire and asked to register 2 different types of voice recordings. They were adults (aged >18 years) who were confirmed by a polymerase chain reaction test to be positive for COVID-19 in Luxembourg and met the inclusion criteria. Statistical methods such as recursive feature elimination for dimensionality reduction, multiple statistical learning methods, and hypothesis tests were used throughout this study. The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) Prediction Model Development checklist was used to structure the research. RESULTS: This study included 259 participants. Younger (aged <35 years) and female participants showed higher rates of ageusia and anosmia. Participants were aged 41 (SD 13) years on average, and the data set was balanced for sex (female: 134/259, 51.7%; male: 125/259, 48.3%). The analyzed symptom was present in 94 (36.3%) out of 259 participants and in 450 (27.5%) out of 1636 audio recordings. In all, 2 machine learning models were built, one for Android and one for iOS devices, and both had high accuracy-88% for Android and 85% for iOS. The final biomarker was then calculated using these models and internally validated. CONCLUSIONS: This study demonstrates that people with COVID-19 who have anosmia and ageusia have different voice features from those without these symptoms. Upon further validation, these vocal biomarkers could be nested in digital devices to improve symptom assessment in clinical practice and enhance the telemonitoring of COVID-19-related symptoms. TRIAL REGISTRATION: Clinicaltrials.gov NCT04380987; https://clinicaltrials.gov/ct2/show/NCT04380987.

In COVID-19 Patients, the Identified Gastrointestinal Symptoms in Tertiary Care Center of India.

Aim: This study aimed to assess the demographic details of coronavirus disease-2019 (COVID-19) patients, their comorbid conditions, preexisting illnesses such as tuberculosis (TB), the prevalence of gastrointestinal (GI) symptoms, duration of GI symptoms, gender-wise distribution of GI symptoms, age-wise distribution of GI symptoms, lab investigation, and computed tomography (CT) scanning was done to record the grading. Materials and methods: In total, 956 COVID-19 patients admitted to an isolation ward of a tertiary care center were screened for 3 months. Patients were confirmed positive for SARS-CoV-2 virus by real-time polymerase chain reaction (RT-PCR) test with a throat swab. Patient's age, demographic details, preexisting illness, and GI symptoms such as fever, impairment of appetite, loss of taste, loss of smell, hiccups, nausea, vomiting, diarrhea, abdominal pain, symptom's duration, history of chronic drug intake, biological markers, CT scanning, and comorbidities were recorded. Based on the provided protocol, standard care management was given to the admitted COVID-19 patients.Statistical analysis was performed using SPSS version 20.0. Frequencies with percentages, median (min, max), Chi-square test, and Mann-Whitney U test were used to test the statistical significance, and a p-value of <0.05 was considered statistically significant. Results: In our prospective study of 956 COVID-19 hospitalized patients, details were analyzed and the results are: the median age was 45 years, 70% of male, 60% were above 35 years, comorbidities like diabetes present in 42%, hypertension in 36%, asthma in 8%, cardiovascular diseases (CVD) in 5%, and history of chronic drug intake in 21%.Among 956 COVID-19 patients, GI symptoms were loss of smell (29.2%), loss of taste (26.4%) for 3 days; nausea (10%), vomiting (7.1%), abdominal pain (12.7%), and fever (42.5%) were observed for 2 days among the 36-45 years of age-group; and the loss of appetite (19%) for 3 days among the age-group of 46-55 years.The loss of appetite (23.7 vs 16.9%) (p= 0.014), taste (32.4 vs 23.8%) (p = 0.005), nausea (14.6 vs 8.2%) (p = 0.003), and vomiting (10.8 vs 5.5%) (p = 0.004) were higher in females than in males. No gender difference was observed in loss of smell (p = 0.057), abdominal pain (12 vs 14.3%) (p = 0.491), hiccups (4 vs 2.1%) (p = 0.132), and fever (41.3 vs 45.3%) (p = 0.329).Females had significantly higher levels of C-reactive protein (CRP) than males (6.1 vs 3.8) (p = 0.002). No gender difference was observed in neutrophil/lymphocyte ratio (NLR) (p = 0.772), ferritin, and lactate dehydrogenase (LDH). CT-grade IV was higher in males than in females (1.7 vs 1.5%), but the rest of the CT grades were higher in females than in males. Conclusion: In conclusion, GI symptoms are the onset of symptoms that are first expressed after being infected with the SARS-CoV-2 virus. Several studies showed the GI symptoms but did not analyze the age and gender that are risk factors for any disease, but our study showed all GI symptoms and their association with age and gender, which will shed light for our clinicians for early symptom identification, diagnosis, and appropriate treatment. How to cite this article: Murugesan M, Govindarajan R, Prakash L, et al. In COVID-19 Patients, the Identified Gastrointestinal Symptoms in Tertiary Care Center of India. Euroasian J Hepato-Gastroenterol 2022;12(1):24-30.

Proportion of New Onset of Anosmia and Its Diagnostic Significance in COVID-19.

OBJECTIVE: This study aimed to know the proportion of new-onset of anosmia and to find its diagnostic significance in coronavirus disease 2019 (COVID-19) patients attending the hospital. Study design and duration: The Indian smell test in COVID-19 by AIIMS Raipur (ISCA-R) was developed for evaluating olfaction in the Indian population. The olfactory function was assessed using the corona scale on anosmia AIIMS Raipur (COSANAr). RESULTS: Out of 256 patients, 171 were males and 85 were females. In the majority of the patients, 75 (29.29%), the COSANAr score "0" was higher on the day of admission compared to the score "3" on the day of discharge with 61 (23.82%) patients. There was no improvement in 134 (52.34%) patients with loss of smell at the time of discharge. CONCLUSION: This study is a step forward in identifying anosmia by ISCA-R at the early stages of the COVID phase. The COSANAr is affordable for the Indian population. It is noticed that most of the patients have mild hyposmia at the time of discharge and anosmia at the admission time.

The 8-Odorant Barcelona Olfactory Test (BOT-8): Validation of a New Test in the Spanish Population During the COVID-19 Pandemic.

BACKGROUND AND OBJECTIVE: Most smell tests are difficult to implement in daily clinical practice owing to their long duration. The aim of the present study was to develop and validate a short, easy-to-perform, and reusable smell test to be implemented during the COVID-19 pandemic. METHODS: The study population comprised 120 healthy adults and 195 patients with self-reported olfactory dysfunction (OD). The 8-Odorant Barcelona Olfactory Test (BOT-8) was used for detection, memory/recognition, and forced-choice identification. In addition, a rose threshold test was performed, and a visual analog scale was applied. The Smell Diskettes Olfaction Test (SDOT) was used for correlation in healthy volunteers, and the University of Pennsylvania Smell Identification Test (UPSIT) was used for patients with OD to establish cut-offs for anosmia and hyposmia. In order to take account of the COVID-19 pandemic, disposable cotton swabs with odorants were compared with the original test. RESULTS: In healthy persons, the mean (SD) BOT-8 score was 100% for detection, 94.5% (1.07) for memory/recognition, and 89.6% (0.86) for identification. In patients with OD, the equivalent values were 86% (32.8), 73.2% (37.9), and 77.1% (34.2), respectively. BOT-8 demonstrated good test-retest reliability, with agreement of 96.7% and a quadratic k of 0.84 (P<.001). A strong correlation was observed between BOT-8 and SDOT (r=0.67, P<.001) and UPSIT (r=0.86, P<.001). Agreement was excellent for disposable cotton swabs, with a k of 0.79 compared with the original test. The cut-off point for anosmia was ≤3 (area under the curve, 0.83; sensitivity, 0.673; specificity, 0.993). CONCLUSION: BOT-8 offers an efficient and fast method for assessment of smell threshold, detection, memory, and identification in daily clinical practice. Disposable cotton swabs with odorants proved to be useful and safe during the COVID-19 pandemic.

Why Does the Omicron Variant Largely Spare Olfactory Function? Implications for the Pathogenesis of Anosmia in Coronavirus Disease 2019.

The omicron variant of severe acute respiratory syndrome coronavirus 2 causes much less olfactory dysfunction than the previous variants. There are several potential mechanisms for how omicron may change tissue tropism and spare olfactory function. The new mutations make omicron more hydrophobic and alkaline than previous variants, which may reduce penetration of the mucus layer. Overall, the new mutations minimally change receptor binding affinity, but entry efficiency into host cells is reduced in cells expressing transmembrane serine protease 2 (TMPRSS2). Because the support cells in the olfactory epithelium abundantly express TMPRSS2, these main target cells in the olfactory epithelium may become infected less by the new omicron variant.