Smell and taste

This chapter provides an up-to-date overview of the nature and causes of chemosensory disturbances in older age, tools for their evaluation, and approaches useful for counselling patients and treating the underlying dysfunction. In addition to the sensory innervation of the olfactory nerve, free nerve endings of the trigeminal nerve are distributed throughout the nasal mucosa. Threshold tests establish the lowest concentration of an odorant that can be perceived or recognised as a quality. Odour identification tests determine the degree of a person's olfactory function. The loss of smell can be quite severe in patients with nasal sinus disease, with most being anosmic or profoundly hyposmic. Severe acute respiratory syndrome coronavirus 2, which causes coronavirus disease 2019, affects chemosensory functions. During the last decade, more extensive research in the area of central nervous diseases has accumulated evidence on neurodegenerative processes and impaired olfaction. Taste function, like olfactory function, declines over the lifespan. © 2022 John Wiley & Sons Ltd. All rights reserved.

Identification of Genes Associated with the Impairment of Olfactory and Gustatory Functions in COVID-19 via Machine-Learning Methods.

The coronavirus disease 2019 (COVID-19), as a severe respiratory disease, affects many parts of the body, and approximately 20-85% of patients exhibit functional impairment of the senses of smell and taste, some of whom even experience the permanent loss of these senses. These symptoms are not life-threatening but severely affect patients' quality of life and increase the risk of depression and anxiety. The pathological mechanisms of these symptoms have not been fully identified. In the current study, we aimed to identify the important biomarkers at the expression level associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection-mediated loss of taste or olfactory ability, and we have suggested the potential pathogenetic mechanisms of COVID-19 complications. We designed a machine-learning-based approach to analyze the transcriptome of 577 COVID-19 patient samples, including 84 COVID-19 samples with a decreased ability to taste or smell and 493 COVID-19 samples without impairment. Each sample was represented by 58,929 gene expression levels. The features were analyzed and sorted by three feature selection methods (least absolute shrinkage and selection operator, light gradient boosting machine, and Monte Carlo feature selection). The optimal feature sets were obtained through incremental feature selection using two classification algorithms: decision tree (DT) and random forest (RF). The top genes identified by these multiple methods (H3-5, NUDT5, and AOC1) are involved in olfactory and gustatory impairments. Meanwhile, a high-performance RF classifier was developed in this study, and three sets of quantitative rules that describe the impairment of olfactory and gustatory functions were obtained based on the optimal DT classifiers. In summary, this study provides a new computation analysis and suggests the latent biomarkers (genes and rules) for predicting olfactory and gustatory impairment caused by COVID-19 complications.

SARS-CoV-2 Effects on Psychophysical Olfactory Scores: Prospective Study With Evaluation Before and 60-Days After Infection.

The aim of this study was to prospectively evaluate the olfactory function in a series of individuals infected with SARS-CoV-2 and who had undergone psychophysical olfactory assessment prior to infection. Individuals unexposed to SARS-CoV-2 infection underwent a psychophysical evaluation of smell with the Sniffin' Sticks test. The subjects were followed prospectively and included in the study if they developed SARS-CoV-2 infection with a second test 60 days after recovery. At the 60-day follow-up of the 41 included subjects, 2 (4.9%) self-reported persistent olfactory dysfunction (OD). The differences between TDI scores before and after infection were statistically significant (37 [interquartile range (IQR), 34.25-39.25] vs 34.75 [IQR, 32.25-38]; p = .021). Analyzing the individual olfactory domains, the differences were significant for threshold (T) (9.75 [IQR, 9-11.25] vs 8.25 [IQR, 7.25-10.25]; p = .009) but not for odor discrimination (D) (p = .443) and identification (I) (p = .159). SARS-CoV-2 causes a significant reduction in the olfactory function, in particular affecting the olfactory threshold, even in subjects who do not self-report an OD.

Prednisolone does not improve olfactory function after COVID-19: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Prednisolone has been suggested as a treatment for olfactory disorders after COVID-19, but evidence is scarce. Hence, we aimed to determine the efficacy of a short oral prednisolone treatment on patients with persistent olfactory disorders after COVID-19. METHODS: We performed a randomized, double-blind, placebo-controlled, single-centered trial in the Netherlands. Patients were included if they were > 18 years old and if they had persistent (> 4 weeks) olfactory disorders within 12 weeks after a confirmed COVID-19 test. The treatment group received oral prednisolone 40 mg once daily for 10 days and the placebo group received matching placebo. In addition, all patients performed olfactory training. The primary outcome was the objective olfactory function on Sniffin' Sticks Test (SST) 12 weeks after the start of treatment, measured in Threshold-Discrimination-Identification (TDI) score. Secondary outcomes were objective gustatory function assessed by the Taste Strip Test (TST) and subjective self-reported outcomes on questionnaires about olfactory, gustatory and trigeminal function, quality of life, and nasal symptoms. The CONSORT 2010 guideline was performed. RESULTS: Between November 2021 and February 2022, we included 115 eligible patients, randomly assigned to the treatment (n = 58) or placebo group (n = 57). No difference in olfactory function between groups was obtained after 12 weeks. Median TDI score on SST was 26.8 (IQR 23.6-29.3) in the placebo group and 28.8 (IQR 24.0-30.9) in the prednisolone group, with a median difference of 2.0 (95% CI 0.75 to 1.5). There was similar improvement on olfactory function in both groups after 12 weeks. Furthermore, on secondary outcomes, we obtained no differences between groups. CONCLUSIONS: This trial shows that prednisolone does not improve olfactory function after COVID-19. Therefore, we recommend not prescribing prednisolone for patients with persistent olfactory disorders after COVID-19. TRIAL REGISTRATION: This trial is registered on the ISRCTN registry with trial ID ISRCTN70794078.

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.

The Association between Olfactory Function and Cognitive Impairment in Older Persons with Cognitive Impairments: A Cross-Sectional Study.

Olfactory function is an emerging topic of research in the fields of cognitive impairment and neurodegenerative diseases. We aimed to confirm the association between olfactory function and cognitive impairment by assessing the olfactory function of older persons with cognitive impairment and identify whether olfactory function is associated with cognitive impairment. For this study, we recruited 117 older people aged ≥65 years with cognitive impairments from a public hospital in Korea. We used the Korean version of the expanded clinical dementia rating scale to evaluate participants' cognitive impairments, and the University of Pennsylvania's smell identification test to assess their olfactory function. Our results indicate a significant negative correlation between olfactory function and all domains of cognitive impairment (memory, orientation, judgement and problem-solving, community affairs, home and hobbies, and personal care). In addition, olfactory function was a factor associated with cognitive impairment in older persons. Therefore, we expect that our results to provide useful data for the development of interventions using olfactory stimulation to improve cognitive function in older persons with cognitive impairment.

Eight-month follow-up of olfactory and gustatory dysfunctions in recovered COVID-19 patients.

PURPOSE: To investigate the recovery of loss of smell and taste among recovered COVID-19 patients. MATERIALS AND METHODS: This cross-sectional follow-up study is a sequel to a study by Biadsee et al. Among the previous study population of 128 non-hospitalized patients, positive for COVID-19 by reverse transcription-polymerase chain reaction (RT-PCR), 97 patients participated in a survey designed for this study. Information and data regarding loss of smell and taste, rate of recovery, xerostomia, and additional symptoms; (Cough, Myalgia, Weakness, Rhinorrhea, Nasal congestion) were collected. RESULTS: A total of 43 men and 54 women were included. Mean age was 37.5 years (range 19-74). Mean follow-up was 229 days (range 191-253). Sixty-five patients reported gustatory dysfunction during the disease of which 61.5% reported full recovery, 38.5% partial recovery. Of 65 patients who reported olfactory impairment during the disease, 52% had full recovery and 48% reported partial recovery of olfactory function. Complete recovery of olfactory function was positively associated with full recovery of gustatory function (p = 0.01). Gender did not significantly affect the recovery of OD and GD (p = 0.45, p = 0.90, respectively). Patients who experienced olfactory dysfunction as an initial symptom had lower rates of olfactory complete recovery (p = 0.043). CONCLUSION: After a mean follow-up of 229 days, complete recovery of smell and taste functions occurred in 52% and 61.5%, respectively. However, dysfunction persisted in 48%-38.5% of patients.

Six-Month Psychophysical Evaluation of Olfactory Dysfunction in Patients with COVID-19.

This study prospectively assessed the 6-month prevalence of self-reported and psychophysically measured olfactory dysfunction in subjects with mild-to-moderate COVID-19. Self-reported smell or taste impairment was prospectively evaluated by SNOT-22 at diagnosis, 4-week, 8-week, and 6-month. At 6 months from the diagnosis, psychophysical evaluation of olfactory function was also performed using the 34-item culturally adapted University of Pennsylvania Smell Identification Test (CA-UPSIT). 145 completed both the 6-month subjective and psychophysical olfactory evaluation. According to CA-UPSIT, 87 subjects (60.0%) exhibited some smell dysfunction, with 10 patients being anosmic (6.9%) and seven being severely microsmic (4.8%). At the time CA-UPSIT was administered, a weak correlation was observed between the self-reported alteration of the sense of smell or taste and olfactory test scores (Spearman's r = -0.26). Among 112 patients who self-reported normal sense of smell at last follow-up, CA-UPSIT revealed normal smell in 46 (41.1%), mild microsmia in 46 (41.1%), moderate microsmia in 11 (9.8%), severe microsmia in 3 (2.3%), and anosmia in 6 (5.4%) patients; however, of those patients self-reporting normal smell but who were found to have hypofunction on testing, 62 out of 66 had a self-reported reduction in sense of smell or taste at an earlier time point. Despite most patients report a subjectively normal sense of smell, we observed a high percentage of persistent smell dysfunction at 6 months from the diagnosis of syndrome coronavirus 2 (SARS-CoV-2) infection, with 11.7% of patients being anosmic or severely microsmic. These data highlight a significant long-term rate of smell alteration in patients with previous SARS-COV-2 infection.

Olfactory Dysfunction: A Highly Prevalent Symptom of COVID-19 With Public Health Significance.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is a global pandemic affecting millions of individuals, killing hundreds of thousands. Although typically described with characteristic symptoms of fever, cough, and shortness of breath, greater understanding of COVID-19 has revealed myriad clinical manifestations. Olfactory dysfunction (OD)-hyposmia and anosmia-has recently been recognized as an important symptom of COVID-19 and increasingly gained traction as a public health tool for identifying COVID-19 patients, in particular otherwise asymptomatic carriers who, unawares, may be major drivers of disease spread. The objective of this study is to review the scientific evidence about anosmia in COVID-19. DATA SOURCES: PubMed, Google Scholar, and Web of Science. REVIEW METHODS: Comprehensive literature search of primary studies pertinent to the objectives of this review using the chosen data sources. CONCLUSIONS: Current evidence shows that OD is highly prevalent in COVID-19, with up to 80% of patients reporting subjective OD and objective olfactory testing potentially showing even higher prevalence. OD is frequently accompanied by taste dysfunction. Up to 25% of COVID-19 patients may experience sudden-onset OD as the first symptom. A large proportion of COVID-19 OD cases may resolve over the period of a few weeks. IMPLICATIONS FOR PRACTICE: Sudden anosmia should be considered a symptom of COVID-19. Assessing for sudden-onset anosmia may increase sensitivity of COVID-19 screening strategies, in particular for identifying patients at the earliest stages of disease. Since many cases of OD due to COVID-19 may resolve in the short term, conservative management, including observation, is reasonable, while advanced imaging is unnecessary.

Mood, Anxiety and Olfactory Dysfunction in COVID-19: Evidence of Central Nervous System Involvement?

OBJECTIVE: The objective of this study was to determine the burden of depressed mood and anxiety in COVID-19, and associated disease characteristics. MATERIALS AND METHODS: This is a prospective, cross-sectional study of 114 COVID-19 positive patients diagnosed using RT-PCR-based testing over a 6-week period. The two-item Patient Health Questionnaire (PHQ-2) and the two-item Generalized Anxiety Disorder questionnaire (GAD-2) were used to measure depressed mood and anxiety level, respectively, at enrollment and for participants' baseline, pre-COVID-19 state. Severity of smell loss, loss of taste, nasal obstruction, rhinorrhea/mucus production, fever, cough, and shortness of breath (SOB) during COVID-19 were assessed. RESULTS: PHQ-2 and GAD-2 significantly (P < .001) increased from baseline to enrollment. PHQ-2 was associated with smell loss (adjusted incidence rate ratio [aIRR] = 1.40, 95% CI, 1.10-1.78, P = .006), age (aIRR = 1.02, 95% CI, 1.01-1.04, P = .006), and baseline PHQ-2 score (aIRR = 1.39, 95% CI, 1.09-1.76, P = .007). GAD-2 score was associated with smell loss (aIRR = 1.29, 95% CI, 1.02-1.62, P = .035), age (aIRR = 1.02, 95% CI, 1.01-1.04, P = .025) and baseline GAD-2 score (aIRR = 1.55, 95% CI, 1.24-1.93, P < .001). Loss of taste also exhibited similar associations with PHQ-2 and GAD-2. PHQ-2 and GAD-2 scores were not associated with severities of any other symptoms during the COVID-19 course. CONCLUSIONS: Despite the occurrence of symptoms-such as SOB-associated with severe manifestations of COVID-19, only the severities of smell and taste loss were associated with depressed mood and anxiety. These results may raise the novel possibility of emotional disturbance as a CNS manifestation of COVID-19 given trans-olfactory tract penetration of the central nervous system (CNS) by coronaviruses. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:2520-2525, 2020.

Validation of a self-administered olfactory and gustatory test for the remotely evaluation of COVID-19 patients in home quarantine.

BACKGROUND: Chemosensitive disorders are very frequent in the early stages of COVID-19 and in paucisymptomatic cases. These patients are typically placed in home quarantine. This study has the aim of validating a new olfactory and gustatory objective evaluation test in these patients. METHODS: Thirty-three home-quarantined COVID-19 patients have undergone a self-administered chemosensitive test the day before the control swab. On this occasion, the patients underwent operator-administered already validated tests. The results were finally compared. RESULTS: The differences between the results of the two tests were not significant for both the olfaction (P =.201) and the taste (P =.180). CONCLUSION: The olfactory and gustatory evaluation by self-administered test can be considered a valid tool, fundamental for obtaining objective qualitative and quantitative data on the extent of chemosensitive disorders in home-quarantined COVID-19 patients.

Objective evaluation of anosmia and ageusia in COVID-19 patients: Single-center experience on 72 cases.

BACKGROUND: The first European case series are detecting a very high frequency of chemosensitive disorders in COVID-19 patients, ranging between 19.4% and 88%. METHODS: Olfactory and gustatory function was objectively tested in 72 COVID-19 patients treated at University Hospital of Sassari. RESULTS: Overall, 73.6% of the patients reported having or having had chemosensitive disorders. Olfactory assessment showed variable degree hyposmia in 60 cases and anosmia in two patients. Gustatory assessment revealed hypogeusia in 33 cases and complete ageusia in one patient. Statistically significant differences in chemosensitive recovery were detected based on age and distance from the onset of clinical manifestations. CONCLUSION: Olfactory and gustatory dysfunctions represent common clinical findings in COVID-19 patients. Otolaryngologists and head-neck surgeons must by now keep this diagnostic option in mind when evaluating cases of ageusia and nonspecific anosmia that arose suddenly and are not associated with rhinitis symptoms.