Trends in clinical trials for olfactory dysfunction in the COVID-19 era.

KEY POINTS: Nearly half of all olfactory dysfunction (OD) clinical trials since 2010 are COVID-19-related. COVID-19-related OD trials are published significantly faster than COVID-19-unrelated trials. High-quality clinical trials and publications are crucial to discovering effective treatments.

Olfactory impairment in COVID-19: Two methods for the assessment of olfactory function.

Background: Olfactory impairment is a major symptom of COVID-19. Is it necessary for COVID-19 patients to perform the detection of olfactory function, even how to select the olfactory psychophysical assessment tool. Methods: Patients infected with SARS-CoV-2 Delta variant were firstly taken into three categories (mild, moderate, and severe) according to the clinical classification. The Odor Stick Identification Test for the Japanese (OSIT-J) and the Simple Olfactory Test were used to assess olfactory function. Moreover, these patients were divided into three groups based on the results of the olfactory degree (euosmia, hyposmia, and dysosmia), too. The statistical analysis of the correlations between olfaction and clinical characteristics of patients were performed. Results: Our study demonstrated that the elderly men of Han were more susceptible to infected SARS-CoV-2, the clinical symptoms of the COVID-19 patients showed a clear correspondence with the disease type and the degree of olfactory disturbance. Whether or not to vaccinate and whether to complete the whole course of vaccination was closely related to the patient's condition. OSIT-J Test and Simple Test were consistent in our work, indicating that olfactory grading would worsen with the aggravation of symptoms. Furthermore, the OSIT-J method maybe better than Simple Olfactory Test. Conclusion: The vaccination has an important protective effect on the general population, and vaccination should be vigorously promoted. Moreover, it is necessary for COVID-19 patients to perform the detection of olfactory function, and the easier, faster and less expensive method for determination of olfactory function should be utilized to COVID-19 patients as the vital physical examination.

Determination of the Prevalence of Postcovid Syndrome and Assessment of the Effectiveness of the Drug Cortexin in the Treatment of Neurological Disorders in Patients with Postcovid Syndrome. Results of the CORTEX Multicenter Clinical and Epidemiological Observational Program.

Objectives. To study the prevalence and clinical manifestations of postcovid syndrome (PCS) in out-patients and to assess the efficacy of treatment with the drug Cortexin at doses of 10 and 20 mg i.m. for 10 days. Materials and methods. A total of 979 patients with PCS from regions of the Russian Federation, Azerbaijan, Kyrgyzstan, and Kazakhstan were studied; mean age was 54.6 ± 4.5 years; duration of COVID-19 was from one month upwards. Investigations involved three visits. The first was on the day of consultation (assessment of complaints, analysis of scale indicators, prescription of drug Cortexin at a dose of 10 or 20 mg i.m. for 10 days). The second visit (telephone consultation) was on day 10-14. The third visit was on day 30 of out-patient treatment. Assessment of patients' status used an asthenia assessment scale (MFI-20), a brief mental state assessment scale (MMSE), the Schulte test, and the Subjective Treatment Quality Assessment Scale. Results. The proportion of patients with PCS was up to 30% of all neurological admissions. The commonest manifestations were: fatigue, general weakness, decreased memory and concentration of attention, vertigo, sleep impairment, irritability, and aggression; less frequent were breathlessness, pain, increased sweating, anosmia, hyposmia, dysgeusia, paresthesia, hair loss, degradation of vision, tachycardia, allergic reactions, menstrual cycle impairments, erectile dysfunction, panic attacks, suicidal ideation, depression and refusal to eat meat. Conclusions: No associations were found between clinical symptomatology and the severity of COVID-19, the volume of lung tissue affected, or different periods of postcovid syndrome. Cortexin was found to be effective at doses of 10 and 20 mg for correcting the cognitive and asthenic manifestations of PCS. Cortexin was found to have anti-anxiety, antidepressant, and anxiolytic effects, which were more marked at the 20-mg dose.

Sudden loss of smell and taste: clinical predictors of coronavirus disease 2019 infection.

OBJECTIVES: This study aimed: to evaluate the association between coronavirus disease 2019 infection and olfactory and taste dysfunction in patients presenting to the out-patient department with influenza-like illness, who underwent reverse transcription polymerase chain reaction testing for coronavirus; and to determine the sensitivity, specificity, and positive and negative predictive values of olfactory and taste dysfunction and other symptoms in these patients. METHODS: Patients presenting with influenza-like illness to the study centre in September 2020 were included in the study. The symptoms of patients who tested positive for coronavirus on reverse transcription polymerase chain reaction testing were compared to those with negative test results. RESULTS: During the study period, 909 patients, aged 12-70 years, presented with influenza-like illness; of these, 316 (34.8 per cent) tested positive for coronavirus. Only the symptoms of olfactory and taste dysfunction were statistically more significant in patients testing positive for coronavirus than those testing negative. CONCLUSION: During the pandemic, patients presenting to the out-patient department with sudden loss of sense of smell or taste may be considered as positive for coronavirus disease 2019, until proven otherwise.

Impact of olfactory dysfunction on quality of life in coronavirus disease 2019 patients: a systematic review.

OBJECTIVE: To outline the impact on quality of life in coronavirus disease 2019 patients with olfactory dysfunction. METHODS: Five databases were searched for articles referring to the impact on quality of life in coronavirus disease 2019 patients with olfactory dysfunction. The search was conducted for the period from November 2019 to April 2021. The search was conducted over one month (May 2021). RESULTS: Four studies that met the objective were included. Altogether, there were 1045 patients. Various questionnaires were used to assess quality of life. Overall, the quality of life deficit affected 67.7 per cent of patients. Quality of life domains investigated include overall quality of life (four studies), food and taste dysfunction (two studies), mental health (two studies), cognitive function (one study), functional outcome (one study) and safety domains (one study). CONCLUSION: Quality of life deficit was reported to be 67.7 per cent among coronavirus disease 2019 patients with olfactory dysfunction. The high prevalence of persistent olfactory dysfunction prompts more serious research, as the long-standing consequences of olfactory dysfunction are detrimental.

Olfactory dysfunction amongst children and adolescents with laboratory confirmed coronavirus disease 2019: a systematic review.

BACKGROUND: Despite the rapidly emerging reports of olfactory dysfunction amongst adult patients with coronavirus disease 2019, cases involving children and adolescents are scarcely reported. The literature was reviewed to elucidate olfactory dysfunction amongst children and adolescents with coronavirus disease 2019. METHODS: A search of the literature published from 1 December 2019 to 30 April 2021 was conducted using four databases, based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and the Cochrane Handbook for Systematic Reviews of Interventions. The search was performed over one month (May 2021). RESULTS: Only 9 articles were identified, with a total of 316 laboratory confirmed coronavirus disease 2019 positive children and adolescents, of whom 156 reported olfactory dysfunction. Four studies reported olfactory dysfunction based on subjective tests; four studies carried out objective assessment. Most studies reported on olfaction recovery. CONCLUSION: The literature review revealed an olfactory dysfunction rate of 49 per cent amongst children and adolescents with coronavirus disease 2019. Persistence of olfactory dysfunction was reported in 7.1 per cent of the patients. Further studies involving objective measures need to be carried out in children and adolescents with coronavirus disease 2019.

Olfactory dysfunction at six months after coronavirus disease 2019 infection.

OBJECTIVE: This study aimed to assess olfactory dysfunction in patients at six months after confirmed coronavirus disease 2019 infection. METHODS: Coronavirus disease 2019 positive patients were assessed six months following diagnosis. Patient data were recoded as part of the adapted International Severe Acute Respiratory and Emerging Infection Consortium Protocol. Olfactory dysfunction was assessed using the University of Pennsylvania Smell Identification Test. RESULTS: Fifty-six patients were included. At six months after coronavirus disease 2019 diagnosis, 64.3 per cent of patients (n = 36) were normosmic, 28.6 per cent (n = 16) had mild to moderate microsmia and 7 per cent (n = 4) had severe microsmia or anosmia. There was a statistically significant association between older age and olfactory dysfunction. Hospital or intensive care unit admission did not lead to worse olfactory outcomes compared to those managed in the out-patient setting. CONCLUSION: At six months after coronavirus disease 2019 diagnosis, approximately two-thirds of patients will be normosmic. This study is the first to describe six-month outcomes for post-coronavirus disease 2019 patients in terms of olfactory dysfunction.

Olfactory Impairment and Close Social Relationships. A Narrative Review.

Olfactory impairment is one of the more unique symptoms of COVID-19 infection and has therefore enjoyed increased public attention in recent months. Olfactory impairment has various implications and consequences ranging from difficulty detecting dangerous pathogens to hindering social functioning and social behaviors. We provide an overview of how olfactory impairment can impact 3 types of close social relationships: family relationships, friendships, and romantic relationships. Evidence is divided into several categories representing potential mechanisms by which olfactory impairment can impact close social relationships: bonding disruptions, decreased social support, missed group-eating experiences, hygiene concerns, and altered sexual behaviors. We conclude with a discussion of emerging future research questions.

Impairment of olfactory and gustatory sensations in severe acute respiratory syndrome corona virus 2 (SARS-CoV-2 virus) disease.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2 virus) disease had first appeared in December 2019 in Wuhan, China, and since then, it has emerged as a global threat to humanity. An early diagnosis and isolation are the most significant measures required to prevent its spread. Recent anecdotal evidence has suggested impairment of olfactory and gustatory sensations associated with corona virus disease (COVID-19). Angiotensin-converting enzyme-2 is an important aspect for the manifestations seen in this deadly viral disease. The associated olfactory and gustatory dysfunction can also lead to partial and/or complete loss of the ability to smell and taste in the early stages of disease onset. Evidence has also suggested that the presence of SARS-CoV-2 nucleic acid in human saliva makes it the carrier of the infectious viral disease and aids in its diagnosis. The present review focuses on the listed clinical manifestations in the form of olfactory and gustatory impairment in SARS-CoV-2 virus disease.

Ethyl alcohol threshold test: a fast, reliable and affordable olfactory Assessment tool for COVID-19 patients.

OBJECTIVE: COVID-19 patients may present mild symptoms. The identification of paucisymptomatic patients is paramount in order to interrupt the transmission chain of the virus. Olfactory loss could be one of those early symptoms which might help in the diagnosis of COVID-19 patients. In this study, we aim to develop and validate a fast, inexpensive, reliable and easy-to-perform olfactory test for the screening of suspected COVID-19 patients. STUDY DESIGN: Phase I was a case-control study and Phase II a transversal descriptive study. SUBJECTS AND METHODS: Olfaction was assessed with the ethyl alcohol threshold test and symptoms with visual analogue scales. The study was designed in two phases: In Phase I, we compared confirmed COVID-19 patients and healthy controls. In Phase II, patients with suspected COVID-19 infection referred for testing were studied. RESULTS: 275 participants were included in Phase I, 135 in Phase II. The ROC curve showed an AUC of 0.749 in Phase I, 0.737 in Phase II. The cutoff value which offered the highest amount of correctly classified patients was ≥ 2 (10% alcohol) for all age intervals. The odds ratio was 8.19 in Phase I, 6.56 in Phase II with a 75% sensitivity. When cases report normal sense of smell (VAS < 4), it misdiagnoses 57.89% of patients detected by the alcohol threshold test. CONCLUSION: The olfactory loss assessed with the alcohol threshold test has shown high sensitivity and odds ratio in both patients with confirmed COVID-19 illness and participants with suspected SARS-CoV-2 infection.