Is Olfactory Testing a Useful Diagnostic Tool to Identify SARS-CoV-2 Infections Early? A Cross-Sectional and Longitudinal Analysis.

BACKGROUND: Genesis and the prognostic value of olfactory dysfunction (OD) in COVID-19 remain partially described. The objective of our study was to characterize OD during SARS-CoV-2 infection and to examine whether testing of OD may be a useful tool in clinical practice in order to early identify patients with SARS-CoV-2 infection. METHODS: Olfactory function assessment was objectively carried out using the u-Smell-it® test. In a cross-sectional study part, we evaluated this test in a control cohort of SARS-CoV-2 negative tested patients, who attended the University Hospital Frankfurt between May 2021 and March 2022. In a second longitudinal study part, sensitivity and specificity of OD was evaluated as a diagnostic marker of a SARS-CoV-2 infection in Frankfurt am Main, Germany in SARS-CoV-2 infected patients and their close contacts. RESULTS: Among 494 SARS-CoV-2 negative tested patients, OD was detected in 45.7% and was found to be significantly associated with the male gender (p < 0.001), higher age (p < 0.001), cardiovascular and pulmonary comorbidities (p < 0.001; p = 0.03). Among 90 COVID-19 positive patients, OD was found in 65.6% and was significantly associated with male gender and positive smoking status (p = 0.04 each). Prevalence and severity of OD were significantly increased in infections with the Delta variant (B.1.617.2) compared to those with the Omicron variant (BA.1.1.529). Diagnostic sensitivity and specificity of OD for diagnosis of SARS-CoV-2 infection were 69% and 64%, respectively. CONCLUSION: OD is common in COVID-19 negative and positive tested patients with significantly different prevalence rates observed between different variants. Diagnostic accuracy of OD is not high enough to implement olfactory testing as a tool in diagnostic routine to early identify patients with a SARS-CoV-2 infection.

Wearing N95 masks decreases the odor discrimination ability of healthcare workers: a self-controlled before-after study.

Objective: During the coronavirus disease 2019 (COVID-19) pandemic, the N95 mask is an essential piece of protective equipment for healthcare workers. However, the N95 mask may inhibit air exchange and odor penetration. Our study aimed to determine whether the use of N95 masks affects the odor discrimination ability of healthcare workers. Methods: In our study, all the participants were asked to complete three olfactory tests. Each test involved 12 different odors. The participants completed the test while wearing an N95 mask, a surgical mask, and no mask. The score for each olfactory test was documented. Results: The olfactory test score was significantly lower when the participants wore N95 masks than when they did not wear a mask (7 vs. 10, p < 0.01). The score was also lower when the participants wore N95 masks than surgical masks (7 vs. 8, p < 0.01). Conclusion: Wearing N95 masks decreases the odor discrimination ability of healthcare workers. Therefore, we suggest that healthcare workers seek other clues when diagnosing disease with a characteristic odor.

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.

Psychophysical assessment of olfactory and gustatory function in post-mild COVID-19 patients: A matched case-control study with 2-year follow-up.

BACKGROUND: The aim of this study was to psychophysically evaluate the prevalence of smell and taste dysfunction 2 years after mildly symptomatic severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection compared to that observed at 1-year follow-up and while considering the background of chemosensory dysfunction in the no-coronavirus disease 2019 (COVID-19) population. METHOD: This is a prospective case-control study on 93 patients with polymerase chain reaction (PCR)-positive SARS-CoV-2 infection and 93 matched controls. Self-reported olfactory and gustatory dysfunction was assessed by 22-item Sino-Nasal-Outcome Test (SNOT-22), item "Sense of smell or taste." Psychophysical orthonasal and retronasal olfactory function and gustatory performance were estimated using the extended Sniffin' Sticks test battery, 20 powdered tasteless aromas, and taste strips test, respectively. Nasal trigeminal sensitivity was assessed by sniffing a 70% solution of acetic acid. RESULTS: The two psychophysical assessments of chemosensory function took place after a median of 409 days (range, 366-461 days) and 765 days (range, 739-800 days) from the first SARS-CoV-2-positive swab, respectively. At 2-year follow-up, cases exhibited a decrease in the prevalence of olfactory (27.9% vs. 42.0%; absolute difference, -14.0%; 95% confidence interval [CI], -21.8% to -2.6%; p = 0.016) and gustatory dysfunction (14.0% vs. 25.8%; absolute difference, -11.8%; 95% CI, -24.2% to 0.6%; p = 0.098). Subjects with prior COVID-19 were more likely than controls to have an olfactory dysfunction (27.9% vs. 10.8 %; absolute difference, 17.2%; 95% CI, 5.2% to 28.8%) but not gustatory dysfunction (14.0% vs. 9.7%; absolute difference, 4.3%; 95% CI, -5.8% to 14.4% p = 0.496) still 2 years after the infection. Overall, 3.2% of cases were still anosmic 2 years after the infection. CONCLUSIONS: Although a proportion of subjects recovered from long-lasting smell/taste dysfunction more than 1 year after COVID-19, cases still exhibited a significant excess of olfactory dysfunction 2 years after SARS-CoV-2 infection when compared to matched controls.

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.

Validation of the local applicability of the 'TIB' Olfactory Test Device in the era of COVID-19.

OBJECTIVE: To evaluate the validity and test-retest reliability of the novel 'TIB' Olfactory Test Device (TIB) and to determine its normative values. METHODS: The study stratified the study subjects into normosmic, hyposmic and anosmic groups according to their olfactory function. The olfactory function of the subjects was evaluated using both the traditional Chinese version of the University of Pennsylvania of Smell Identification Test (UPSIT-TC) and the TIB. The normosmic group was used to retest with the UPSIT-TC and TIB at an inter-test interval of at least 7 days. The cut-off scores of TIB among the three different groups were determined by receiver operating characteristic curve analysis. RESULTS: This study enrolled 180 subjects: 60 in each group. The mean scores of TIB were 44.1 for the normosmic group, 27.5 for the hyposmic group and 10.9 for the anosmic group. The TIB scores were significantly different across the three groups. There was a significant correlation between the first and second TIB tests (r = 0.506). The cut-off scores were 41 for normosmic subjects and 24 for hyposmic subjects. CONCLUSION: The validity and test-retest reliability results suggest that the TIB is an appropriate olfactory test for the Taiwanese population.

Comparison of the Healing Effect of Nasal Saline Irrigation with Triamcinolone Acetonide Versus Nasal Saline Irrigation alone in COVID-19 Related Olfactory Dysfunction: A Randomized Controlled Study.

There is no routinely determined treatment for olfactory dysfunction because of COVID-19. Saline irrigation and nasal corticosteroid treatments are safe and inexpensive methods, and have low side effects. In our study, we argue that saline nasal irrigation and topical corticosteroid treatment can be used in the treatment of patients with olfactory loss in all areas of rhinology. A total of 150 patients who admitted to our clinic with other symptoms or with only acute odor loss, diagnosed with COVID-19 with RT-PCR were divided into 3 equal groups.Fifty patients in Group 1 were not given any extra treatments. The other 50 patients in Group 2 were given saline irrigation for treatment; and the 50 people in Group 3 were given both saline irrigation and nasal steroid spray for treatment. The "Subjective Olfactory Capability (SOC)" was used for olfactory function evaluation of patients. Self-Rating Olfactory Score (SROS), and Olfactory Dysfunction Duration (ODD) were recorded on the 1st, 15th and 30th days. SROS of the group receiving Nasal Saline + Triamcinolone Acetonide treatment on the 30th day was significantly higher than in other groups ( p -1-3 = 0.018,  p 2-3  = 0.033). Also, the ODD was significantly reduced in this group compared to other groups ( p -1-3  = 0.022,  p 2-3  = 0.028,). Topical triamcinolone treatment was found to be successful in the treatment of olfactory dysfunction due to COVID-19. Nasal steroids, which are both inexpensive and have low side effect profiles, can be used safely in the treatment of patients with olfactory losses.

Olfactory Dysfunction is Associated with More Severe Clinical Course in COVID-19.

To perform a quantitative olfactory test in positive COVID19 RT-PCR admitted patients and asymptomatic ones, to evaluate the association between hyposmia and disease severity. This is a Cross sectional study. Ninety-one patients including 68 inpatients and 23 asymptomatic healthcare workers with positive COVID-19 RT-PCRs. Methods: Demographics and clinical characteristics were collected. Iran Smell Identification Test (IR-SIT), a highly accurate 6-odorant test was used to evaluate the reliability of self-reported hyposmia and determine the correlation of the measured olfactory dysfunction with disease severity. Twenty-two of 91 patients (24%) reported hyposmia, while 41/91 (45%) patients had measurable olfactory dysfunction (IR-SIT score 1-4, p < 0.05). Mean age of the 68 inpatients and 23 asymptomatic patients were 43.97 ± 16.13 years; M:F 43:25, and 43.87 ± 12.76 years; M:F 8:15 respectively. Of 68 patients, 20 were graded as severe, and 48/68 had mild course of disease. IR-SIT detected hyposmia in 80% of patients with severe disease, and 50% with mild disease, respectively. The risk of disease severity was significantly increased for patients with olfactory dysfunction and was detected 4 times higher when compared to patients with mild disease (OR 4, 95% CI: 1.166-13.728, p = 0.028). Olfactory Dysfunction was present in 80% of patients with severe course. The risk of disease severity is significantly increased with olfactory dysfunction in admitted patients.

Diagnostic Value of Butanol Threshold Test in COVID-19 Related Olfactory Dysfunction.

Olfactory and taste dysfunction has been reported as a specific, preliminary symptom in COVID-19, but a few comparative studies with quantitative tests are reported. In this study, we aimed to compare the butanol olfactory threshold values between COVID-19 patients and healthy volunteers.A cross-sectional study was designed. A total of 53 patients were included in the COVID-19 group and the control group. The definitive diagnosis of COVID-19 was made with reverse-transcription polymerase chain reaction (RT-PCR) test. Frequency of odor and taste dysfunction and other head and neck system-specific and other symptoms were recorded. Afterward, olfactory threshold values determined according to Connecticut Chemosensory Clinical Research Center (CCCRC) test principle for study groups. 21 patients included in the COVID-19 group and 32 patients in the control group. Symptom onset time was 7.1 ± 3.1 (min: 3, max: 14) days for COVID-19 patients. The most common symptom in the otolaryngology system was olfactory dysfunction (n = 15, 71.4%). The butanol olfactory threshold value was determined as an average of 4.4 ± 1.9 in the COVID-19 group and 6.4 ± 0.8 in the control group (p < 0.001, 95% CI 2.9-1.0). The sensitivity of the butanol threshold test for COVID-19 related olfactory dysfunction was 80.0% and the specificity was 66.6%. For differential, early and initial, diagnosis of COVID-19, complaint of the smell dysfunctions, and impairment butanol threshold may be a distinctive indicator.

Evaluation of predictive value of olfactory dysfunction, as a screening tool for COVID-19.

OBJECTIVES: At the end of 2019, SARS-CoV-2 was identified, the one responsible for the COVID-19 disease. Between a 5.1% and a 98% of COVID-19 patients present some form of alteration in their sense of smell. The objective of this study is to determine the diagnostic yield of the smell dysfunction as screening tool for COVID-19. METHODS: Cross-sectional, observational, and pro-elective study was performed in a tertiary care hospital from May 25th to June 30th, 2020. One hundred and thirty-nine patients were included in the study. Demographic characteristics were collected from anamnesis. A Self-Perception Questionnaire and psychophysical olfactory test (POT) were applied to all participants. The presence of SARS-CoV2, was detected by RT-PCR methods. RESULTS: 51.7% of patients were SARS-CoV-2 positive. A sensitivity of 50% was obtained for the self-perception questionnaire as a screening tool for SARS-CoV2, with a specificity of 80.59%. The positive predictive value (PPV) was of 73.46%, the negative predictive value (NPV) was of 60%. The POT as a screening tool had a PPV of 82.35%, a NPV of 52.45%, a LR+ of 4.34, a LR- 0.84. The combination of anosmia (according to the POT) plus cough and asthenia got an OR of 8.25 for the SARS CoV-2 infection. CONCLUSION: There is a strong association between olfactory dysfunction and COVID-19. However, it is not really efficient in the screening of SARS-CoV-2 infection and thus, they should not be considered as a single diagnostic instrument. LEVEL OF EVIDENCE: 4.

Gaining Back What Is Lost: Recovering the Sense of Smell in Mild to Moderate Patients After COVID-19.

The purpose of our cohort study was to quantify olfactory deficits in Coronavirus disease 2019 (COVID-19) patients using Sniffin' Sticks and a pre-post design to evaluate olfactory recovery. Thirty adult patients with laboratory-confirmed mild to moderate forms of COVID-19 underwent a quantitative olfactory test performed with the Sniffin' Sticks test (SST; Burghardt, Wedel, Germany), considering olfactory threshold (T), odor discrimination (D), and odor identification (I). Results were presented as a composite TDI score (range 1-48) that used to define functional anosmia (TDI ≤ 16.5), hyposmia (16.5 < TDI < 30.5), or functionally normal ability to smell (TDI ≥ 30.5). Patients also self-evaluated their olfactory function by rating their ability to smell on a visual analogue scale (Visual Analog Scale rating) and answering a validated Italian questionnaire (Hyposmia Rating Scale). Patients were tested during hospitalization and about 2 months after symptoms onset. During the hospitalization, the overall TDI score indicated that our cohort had impairments in their olfactory ability (10% was diagnosed with anosmia and more than 50% were hyposmic). Almost all patients showed a significant improvement at around 1 month following the first test and for all the parts of the SST except for odor identification. None of the subjects at 1 month was still diagnosed with anosmia. We also quantified the improvement in the TDI score based on initial diagnosis. Anosmic subjects showed a greater improvement than hyposmic and normosmic subjects. In conclusion, within a month time window and 2 months after symptoms' onset, in our cohort of patients we observed a substantial improvement in the olfactory abilities.

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.