Development of parallel forms of a brief smell identification test useful for longitudinal testing.

Although there are numerous brief odor identification tests available for quantifying the ability to smell, none are available in multiple parallel forms that can be longitudinally administered without potential confounding from knowledge of prior test items. Moreover, empirical algorithms for establishing optimal test lengths have not been generally applied. In this study, we employed and compared eight machine learning algorithms to develop a set of four brief parallel smell tests employing items from the University of Pennsylvania Smell Identification Test that optimally differentiated 100 COVID-19 patients from 132 healthy controls. Among the algorithms, linear discriminant analysis (LDA) achieved the best overall performance. The minimum number of odorant test items needed to differentiate smell loss accurately was identified as eight. We validated the sensitivity of the four developed tests, whose means and variances did not differ from one another (Bradley-Blackwood test), by sequential testing an independent group of 32 subjects that included persons with smell dysfunction not due to COVID-19. These eight-item tests clearly differentiated the olfactory compromised subjects from normosmics, with areas under the ROC curve ranging from 0.79 to 0.83. Each test was correlated with the overall UPSIT scores from which they were derived. These brief smell tests can be used separately or sequentially over multiple days in a variety of contexts where longitudinal olfactory testing is needed.

Olfactory Training Impacts Olfactory Dysfunction Induced by COVID-19: A Pilot Study.

INTRODUCTION: Olfactory dysfunction is one of the main symptoms of COVID-19 and may last beyond resolution of the infection. The most promising intervention for post-viral olfactory dysfunction is olfactory training (OT), which involves exposing the olfactory system to a range of odors daily. This approach is thought of promoting the regeneration of olfactory receptor cells, but its effectiveness in patients with post-COVID-19 olfactory dysfunction has yet to be confirmed. METHODS: This double-blind randomized pilot study compared the effectiveness of OT versus placebo in the treatment of post-COVID-19 olfactory dysfunction. Twenty-five participants were recruited in each group. OT protocol consisted of sniffing 4 scents (rose, orange, clove, and eucalyptus) for 5 min twice daily for 12 weeks. Olfactory function was assessed before and after the training using (1) a validated odor identification test (UPSIT-40) and (2) a 10-point visual analog scale; we further assessed the presence of (3) parosmia. RESULTS: While we did not observe any effect of OT on olfactory test scores, we observed a significant improvement of subjective olfactory function in the intervention group, while no such effect was observed in the placebo group. Finally, the frequency of parosmia was significantly lower in the intervention group. CONCLUSIONS: This study highlights an increase in subjective but not objective olfactory function when performing OT for 12 weeks. Further, parosmia seems to be positively affected by OT. These results may serve as a starting point for larger scale studies to assess the efficacy of OT for treatment of post-COVID-19 olfactory dysfunction.

Acupuncture for olfactory dysfunction in infected COVID-19 patients: study protocol for a randomized, sham-controlled clinical trial

Objective Olfactory dysfunction (OD) is a common symptom of Corona Virus Disease 2019 (COVID-19). It is defined as the reduced or distorted ability to smell during sniffing (orthonasal olfaction) and represents one of the early symptoms in the clinical course of COVID-19 infection. A large online questionnaire-based survey has shown that some post-COVID-19 patients had no improvement 1 month after discharge from the hospital. Therefore, this clinical trial was designed to explore the efficacy of acupuncture for OD in COVID-19 infected patients and to determine whether acupuncture could have benefits over sham acupuncture for OD in post-COVID-19 patients. Methods This is a single-blind, randomized controlled, cross-over trial. We plan to recruit 40 post-COVID-19 patients with smell loss or smell distortions lasting for more than 1 month. Qualified patients will be randomly allocated to the intervention group (real acupuncture) or the control group (sham acupuncture) at a 1:1 ratio. Each patient will receive 8 sessions of treatment over 4 weeks (Cycle 1) and a 2-week follow-up. After the follow-up, the control group will be subjected to real acupuncture for another 4 weeks (Cycle 2), and the real acupuncture group will undergo the 4-week sham acupuncture. The primary outcomes will be the score changes on the questionnaire of olfactory functioning and olfaction-related quality of life at week 6, 8, 12, and 14 from the baseline. The secondary outcomes will be the changes in the olfactory test score at week 6 and 12 from the baseline measured by using the Traditional Chinese version of the University of Pennsylvania Smell Identification Test (UPSIT-TC). Discussion The results of this trial will help to determine the effectiveness of acupuncture for OD in post-COVID-19 patients. This may provide a new treatment option for patients.

Intranasal Corticosteroid Treatment on Recovery of Long-Term Olfactory Dysfunction Due to COVID-19.

BACKGROUND AND AIMS: Olfactory dysfunction is a recognized manifestation in patients infected with Coronavirus Disease 2019 (COVID-19). This investigation aimed to assess the effect of mometasone furoate intranasal spray on the improvement of smell dysfunction in post-COVID-19 patients. MATERIALS AND METHODS: This randomized placebo-controlled trial included 80 non-hospitalized adult patients who had persistent anosmia or severe microsmia for more than 4 weeks due to COVID-19 infection. The participants were randomly allocated to the intervention or placebo group to receive mometasone furoate nasal spray or sodium chloride intranasal spray during 4 weeks of follow-up, respectively. The patients' olfactory dysfunction was assessed in terms of visual analog scale (VAS), and smell test score according to the modified version of the University of Pennsylvania smell identification test for the Iranian population. RESULTS: A total of 70 participants completed the follow-up period and were analyzed in this study. By comparing the olfactory scores including smell test and VAS scores, no significant differences were found between case and control groups at baseline, 2, and 4 weeks intervals. However, the change of both olfactory scores at pre to post-treatment intervals and 2-4 weeks was significantly higher in the mometasone group relative to the placebo group. At post-treatment, the frequency of anosmia was 22.9% reduced in the case group compared to the control group. CONCLUSION: Overall, there was no significant difference in olfactory dysfunction between the two groups during follow-up. However, based on the significant between-group difference in terms of olfactory scores changes, it seems that the nasal corticosteroids may be a positive effect on the recovery process of patients who received more than 2 weeks. LEVEL OF EVIDENCE: 2 Laryngoscope, 132:2209-2216, 2022.

Analysis of Prevalence and Predictive Factors of Long-Lasting Olfactory and Gustatory Dysfunction in COVID-19 Patients.

BACKGROUND: Although smell and taste disorders are highly prevalent symptoms of COVID-19 infection, the predictive factors leading to long-lasting chemosensory dysfunction are still poorly understood. METHODS: 102 out of 421 (24.2%) mildly symptomatic COVID-19 patients completed a second questionnaire about the evolution of their symptoms one year after the infection using visual analog scales (VAS). A subgroup of 69 patients also underwent psychophysical evaluation of olfactory function through UPSIT. RESULTS: The prevalence of chemosensory dysfunction decreased from 82.4% to 45.1% after 12 months, with 46.1% of patients reporting a complete recovery. Patients older than 40 years (OR = 0.20; 95% CI: [0.07, 0.56]) and with a duration of loss of smell longer than four weeks saw a lower odds ratio for recovery (OR = 0.27; 95% CI: [0.10, 0.76]). In addition, 28 patients (35.9%) reported suffering from parosmia, which was associated with moderate to severe taste dysfunction at the baseline (OR = 7.80; 95% CI: [1.70, 35.8]). Among the 69 subjects who underwent the UPSIT, 57 (82.6%) presented some degree of smell dysfunction, showing a moderate correlation with self-reported VAS (r = -0.36, p = 0.0027). CONCLUSION: A clinically relevant number of subjects reported persistent chemosensory dysfunction and parosmia one year after COVID-19 infection, with a moderate correlation with psychophysical olfactory tests.

Intensive Olfactory Training in Post-COVID-19 Patients: A Multicenter Randomized Clinical Trial.

BACKGROUND: Olfactory dysfunction (OD)-including anosmia and hyposmia-is a common symptom of COVID-19. Previous studies have identified olfactory training (OT) as an important treatment for postinfectious OD; however, little is known about its benefits and optimizations after SARS-CoV-2 infection. OBJECTIVE: This study aimed to assess whether olfactory training performance can be optimized using more fragrances over a shorter period of time in patients with persistent OD after COVID-19. In addition, we determined the presence of other variables related to OD and treatment response in this population. METHODS: This multicenter randomized clinical trial recruited 80 patients with persistent OD and prior COVID-19 infection for less than 3 months. The patients were divided into 2 groups receiving either 4 or 8 essences over 4 weeks. Subjective assessments and the University of Pennsylvania Smell Identification Test (UPSIT) were performed before and after the treatment. RESULTS: Significant olfactory improvement was measured subjectively and using the UPSIT in both groups; however, no significant differences between the groups were observed. Additionally, the presence of olfactory fluctuations was associated with higher UPSIT scores. CONCLUSION: These data suggest that training intensification by increasing the number of essences for 4 weeks does not show superiority over the classical method. Moreover, fluctuant olfaction seems to be related to a higher score on the UPSIT.

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.

Quick Olfactory Sniffin' Sticks Test (Q-Sticks) for the detection of smell disorders in COVID-19 patients.

BACKGROUND: Coronavirus disease (COVID-19) infection represents a worldwide critical health burden from the sanitary perspective. This disease's symptoms range from a mild flu-like form to a severe life-threatening respiratory disease and respiratory failure. Several patients, however, remain paucisymptomatic. Among the symptoms that seem relevant are the changes in taste and smell, regardless of the disease's severity. METHODS: Data from patients affected by COVID-19 infection, hospitalized from 15 to 29 April, 2020, were analyzed. Questionnaires about smell, taste, and nasal function were administered to all, and a proportion also received the Quick olfactory Sniffin' Sticks Test (q-Sticks) to objectivate the presence of anosmia or hyposmia. The results of instruments and Q-Sticks were then compared. RESULTS: Thirty-seven patients (20 males, 54.1%), with a mean age 0f 69.19 years (SD = 17.96; median 76, IQR: 63-82) were evaluated. Among the patients, 8 (22%) were asymptomatic. Out of the remaining 29 patients, 28 (97%) had fever, 19 (66%) asthenia, 11 (38%) dry cough, 10 (34%) dyspnea, and 6 (21%) gastroenteric symptoms. The q-Sticks test was performed on 27 patients and showed that 6 with anosmia, and 16 patients had hyposmia, where only 5 (14%) patients complained of loss of smell by conducting the questionnaires. CONCLUSION: Although olfactory disturbances may be secondary to other factors, a sudden onset of anosmia or hyposmia should be assessed as a possible symptom of COVID-19 infection. The use of questionnaires or anamnestic collection is sometimes not enough, while adding to them a simple test such as the q-Sticks test can provide more accurate and reliable data. A simple, easy-to-perform, and reliable tool (q-Sticks) for olfactory disorders assessment can be administered to identify the real size of anosmia in patients with COVID-19 infection and detect the early stage of infection or paucisymptomatic patients, therefore becoming important to reduce the spreading of the pandemic.

Prevalence and reversibility of smell dysfunction measured psychophysically in a cohort of COVID-19 patients.

BACKGROUND: Considerable evidence suggests that smell dysfunction is common in coronavirus disease-2019 (COVID-19). Unfortunately, extant data on prevalence and reversibility over time are highly variable, coming mainly from self-report surveys prone to multiple biases. Thus, validated psychophysical olfactory testing is sorely needed to establish such parameters. METHODS: One hundred severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-positive patients were administered the 40-item University of Pennsylvania Smell Identification Test (UPSIT) in the hospital near the end of the acute phase of the disease. Eighty-two were retested 1 or 4 weeks later at home. The data were analyzed using analysis of variance and mixed-effect regression models. RESULTS: Initial UPSIT scores were indicative of severe microsmia, with 96% exhibiting measurable dysfunction; 18% were anosmic. The scores improved upon retest (initial test: mean, 21.97; 95% confidence interval [CI], 20.84-23.09; retest: mean, 31.13; 95% CI, 30.16-32.10; p < 0.0001); no patient remained anosmic. After 5 weeks from COVID-19 symptom onset, the test scores of 63% of the retested patients were normal. However, the mean UPSIT score at that time continued to remain below that of age- and sex-matched healthy controls (p < 0.001). Such scores were related to time since symptom onset, sex, and age. CONCLUSION: Smell loss was extremely common in the acute phase of a cohort of 100 COVID-19 patients when objectively measured. About one third of cases continued to exhibit dysfunction 6 to 8 weeks after symptom onset. These findings have direct implications for the use of olfactory testing in identifying SARS-CoV-2 carriers and for counseling such individuals with regard to their smell dysfunction and its reversibility.

Acute Olfactory Dysfunction-A Primary Presentation of COVID-19 Infection.

COVID-19 is a zoonotic illness caused by a new strain of coronavirus and has recently been declared a pandemic by the World Health Organization, with an estimated fatality rate of 1% to 2%. Early identification and isolation of patients in the preliminary infective stage has been a mainstay of most governmental strategies in order to limit transmission. Four otherwise healthy patients presented to a specialist open access Ear, Nose & Throat Clinic in central London with acute total or subtotal loss of their sense of smell in a single one-week period, coinciding with rapid escalation of COVID-19 infection in the indigenous population. The diagnosis was confirmed by the validated University of Pennsylvania Smell Identification Test (UPSIT) in 3. Endoscopic examination and magnetic resonance imaging (2 cases) excluded a range of alternative potential pathological conditions. Covid-19 antibody testing carried out 6 to 8 weeks after the onset of nasal symptoms showed positive immunoglobulin G antibodies in 3 of the 4 patients. Acute severe anosmia is therefore almost certainly an unusual presenting local nasal feature of a COVID-19 viral infection. All 4 patients achieved significant partial olfactory recovery by one week after treatment with subjective ratings of 40% to 85% of normal (mean 60%) and complete olfaction recovery after 2 to 3 weeks in all 4 patients. The significance, possible pathogenesis, and public health implications are highlighted and discussed.

Is SARS-CoV-2 (COVID-19) postviral olfactory dysfunction (PVOD) different from other PVOD?

BACKGROUND: The SARS-CoV-2 virus continues to spread rapidly across the globe afflicting many with Coronavirus Disease 2019 (COVID-19). As the infection rates rise, a growing number of SARS-CoV-2 positive individuals have been reported to complain of olfactory disturbances at an alarming rate. Postviral olfactory dysfunction (PVOD) is a well-known phenomenon that may explain the olfactory dysfunction reported by SARS-CoV-2 infected individuals. METHODS: A scoping literature review was performed to identify studies that investigated the mechanisms of postviral olfactory dysfunction. Studies demonstrating pathophysiological, histological, immunochemical, and epidemiological outcomes of PVOD were included. RESULTS: Fourteen studies were included in addition to one international news article. Three studies reported destruction of the olfactory epithelium following intranasal inoculation of various viral strains in mice. Three studies isolated pathogenic, anosmia inciting viruses (Parainfluenza virus, Human Coronavirus, Rhinovirus) through nucleic acid amplification. Eleven studies demonstrated female predilection in patients with PVOD and COVID-19 associated olfactory dysfunction, of which the majority were over 50 years old. CONCLUSIONS: PVOD and COVID-19 associated olfactory dysfunction demonstrates considerable similarities in epidemiological trends and disease sequela of other viruses to suggest identical pathophysiological mechanisms. Further studies such as intranasal inoculation and histological biopsies are needed to support our hypothesis.

Smell dysfunction: a biomarker for COVID-19.

BACKGROUND: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), is responsible for the largest pandemic since the 1918 influenza A virus subtype H1N1 influenza outbreak. The symptoms presently recognized by the World Health Organization are cough, fever, tiredness, and difficulty breathing. Patient-reported smell and taste loss has been associated with COVID-19 infection, yet no empirical olfactory testing on a cohort of COVID-19 patients has been performed. METHODS: The University of Pennsylvania Smell Identification Test (UPSIT), a well-validated 40-odorant test, was administered to 60 confirmed COVID-19 inpatients and 60 age- and sex-matched controls to assess the magnitude and frequency of their olfactory dysfunction. A mixed effects analysis of variance determined whether meaningful differences in test scores existed between the 2 groups and if the test scores were differentially influenced by sex. RESULTS: Fifty-nine (98%) of the 60 patients exhibited some smell dysfunction (mean [95% CI] UPSIT score: 20.98 [19.47, 22.48]; controls: 34.10 [33.31, 34.88]; p < 0.0001). Thirty-five of the 60 patients (58%) were either anosmic (15/60; 25%) or severely microsmic (20/60; 33%); 16 exhibited moderate microsmia (16/60; 27%), 8 mild microsmia (8/60; 13%), and 1 normosmia (1/60; 2%). Deficits were evident for all 40 UPSIT odorants. No meaningful relationships between the test scores and sex, disease severity, or comorbidities were found. CONCLUSION: Quantitative smell testing demonstrates that decreased smell function, but not always anosmia, is a major marker for SARS-CoV-2 infection and suggests the possibility that smell testing may help, in some cases, to identify COVID-19 patients in need of early treatment or quarantine.