Association between chemosensory impairment with neuropsychiatric morbidity in post-acute COVID-19 syndrome: results from a multidisciplinary cohort study.

Preliminary methodologically limited studies suggested that taste and smell known as chemosensory impairments and neuropsychiatric symptoms are associated in post-COVID-19. The objective of this study is to evaluate whether chemosensory dysfunction and neuropsychiatric impairments in a well-characterized post-COVID-19 sample. This is a cohort study assessing adult patients hospitalized due to moderate or severe forms of COVID-19 between March and August 2020. Baseline information includes several clinical and hospitalization data. Further evaluations were made using several different reliable instruments designed to assess taste and smell functions, parosmia, and neuropsychiatric disorders (using standardized psychiatric and cognitive measures). Out of 1800 eligible individuals, 701 volunteers were assessed on this study. After multivariate analysis, patients reporting parosmia had a worse perception of memory performance (p < 0.001). Moderate/severe hypogeusia was significantly associated with a worse performance on the word list memory task (p = 0.012); Concomitant moderate/severe olfactory and gustatory loss during the acute phase of COVID-19 was also significantly associated with episodic memory impairment (p = 0.006). We found a positive association between reported chemosensory (taste and olfaction) abnormalities and cognition dysfunction in post-COVID-19 patients. These findings may help us identify potential mechanisms linking these two neurobiological functions, and also support the speculation on a possible route through which SARS-CoV-2 may reach the central nervous system.

Association of air pollution with olfactory identification performance of São Paulo residents: a cross-sectional study.

OBJECTIVE: Exposure to particulate matter of 10 µm or less in diameter (PM10) has been implicated in pulmonary and cardiovascular diseases. However, the effect of PM10 on olfaction has not been well established. We estimated individual acute and chronic PM10 exposure levels in a large Brazilian cohort and related them to the ability to identify odors. METHODS: Adults from São Paulo (n = 1358) were recruited from areas with different levels of air pollution. To verify individual exposure to air pollution, the averages of 30, 60, 90, 180 and 364 days of PM10 were interpolated to subjects' zip codes using the kriging method. Olfactory identification performance was tested using the University of Pennsylvania Smell Identification Test (UPSIT®). Multiple linear regressions were used to calculate the effect of air pollution on olfactory identification performance, controlling for demographic and other variables that affect the sense of smell. RESULTS: Acute exposures to PM10 were related to worse UPSIT® scores, including 30- (ß = - 0.94, 95% Confidence Interval [CI] - 0.98, - 0.89), 60- (ß = - 1.09, 95% CI = - 1.13, - 1.04) and 90-day intervals (ß = - 1.06, 95% CI - 1.10, - 1.02) (reference for ß: 1 µm/m3 increase in PM10 exposure per point decrease in UPSIT® score). Chronic exposures were also associated with worse olfaction for both 180- (ß = - 1.06, 95% CI - 1.10, - 1.03) and 364-day (ß = - 0.87, 95% CI - 0.90, - 0.84) intervals. As in prior work, men, older, low-income, and low-schooling people demonstrated worse olfactory performance. CONCLUSION: Acute and chronic exposure to PM10 is strongly associated with olfactory identification performance in Brazilian adults. Understanding the mechanisms which underlie these relationships could help to improve chemosensory function with a large public health impact.

Post-acute sequelae of SARS-CoV-2 infection: relationship of central nervous system manifestations with physical disability and systemic inflammation.

BACKGROUND: Despite the multitude of clinical manifestations of post-acute sequelae of SARS-CoV-2 infection (PASC), studies applying statistical methods to directly investigate patterns of symptom co-occurrence and their biological correlates are scarce. METHODS: We assessed 30 symptoms pertaining to different organ systems in 749 adults (age = 55 ± 14 years; 47% female) during in-person visits conducted at 6-11 months after hospitalization due to coronavirus disease 2019 (COVID-19), including six psychiatric and cognitive manifestations. Symptom co-occurrence was initially investigated using exploratory factor analysis (EFA), and latent variable modeling was then conducted using Item Response Theory (IRT). We investigated associations of latent variable severity with objective indices of persistent physical disability, pulmonary and kidney dysfunction, and C-reactive protein and D-dimer blood levels, measured at the same follow-up assessment. RESULTS: The EFA extracted one factor, explaining 64.8% of variance; loadings were positive for all symptoms, and above 0.35 for 16 of them. The latent trait generated using IRT placed fatigue, psychiatric, and cognitive manifestations as the most discriminative symptoms (coefficients > 1.5, p < 0.001). Latent trait severity was associated with decreased body weight and poorer physical performance (coefficients > 0.240; p ⩽ 0.003), and elevated blood levels of C-reactive protein (coefficient = 0.378; 95% CI 0.215-0.541; p < 0.001) and D-dimer (coefficient = 0.412; 95% CI 0.123-0.702; p = 0.005). Results were similar after excluding subjects with pro-inflammatory comorbidities. CONCLUSIONS: Different symptoms that persist for several months after moderate or severe COVID-19 may unite within one latent trait of PASC. This trait is dominated by fatigue and psychiatric symptoms, and is associated with objective signs of physical disability and persistent systemic inflammation.

Safety and efficacy of superior turbinate biopsies as a source of olfactory epithelium appropriate for morphological analysis.

PURPOSE: There is no standardized approach for preserving olfactory function in the side of the nose where biopsy of the olfactory epithelium (OE) is performed. Moreover, a gold standard technique for obtaining human OE in vivo is still lacking. We determined the efficacy of obtaining good-quality OE specimens suitable for pathological analysis from the lower half of the superior turbinate and verified the safety of this procedure in maintaining bilateral and unilateral olfactory function. METHODS: In 21 individuals without olfactory complaints and who had undergone septoplasty and inferior turbinectomy OE biopsy was made during septoplasty. Olfactory function, both unilateral and bilateral, was assessed using the University of Pennsylvania Smell Identification Test (UPSIT) before and 1 month after the procedure. Specimens were marked with the olfactory marker protein for confirmation of OE presence. RESULTS: Ninety percent of the samples contained OE, although clear histological characterization was possible from only 62%. There was no deterioration of UPSIT scores either bilaterally or unilaterally on the side of the biopsy. Patients also maintained the ability to identify individual odorants. CONCLUSION: Biopsies of the lower half of the superior turbinate do not affect olfactory function and show strong efficacy in yielding OE tissue and moderate efficacy for yielding tissue appropriate for morphological analysis. Future studies are needed to assess the safety of this procedure in other OE regions.

Olfactory symptoms reported by migraineurs with and without auras.

OBJECTIVE: Olfaction-related symptoms accompany migraine attacks and some, such as osmophobia, may be useful in differentiating migraine from other types of headaches. However, the types and frequencies of olfactory symptoms associated with migraine have not been well characterized. The goal of this study was to better characterize the olfactory symptoms of migraine. METHODS: A cross-sectional study was devised. One hundred and thirteen patients who met the International Classification of Headache Disorders II criteria for migraine were administered a new 65-item questionnaire specifically focused on olfaction-related experiences (eg, odor-related triggers, osmophobia, cacosmia, phantosmia, olfactory hallucinations, olfactory hypersensitivity, and self-perceived olfactory function). Visual analog scale ratings and frequencies were computed and compared between migraineurs with and without auras using t-tests and chi-square analyses. RESULTS: While osmophobia was present in 95.5% of the patients, the prevalence of other olfaction-related symptoms was much lower (interictal olfactory hypersensitivity [IOH], 14.1%; olfactory hallucinations, 6.2%; phantosmia, 4.4%; cacosmia/euosmia, 2.6%). Migraine was commonly triggered by odors (90.2%), with perfume being the most common trigger (95.1%), followed by cleaning products (81.3%), cigarette smoke (71.5%), and motor vehicle exhaust (70.5%). No significant differences in symptom frequencies were apparent between migraineurs with or without auras (P > .40). Interestingly, patients with IOH reported being less likely to experience osmophobia and odor-triggered crisis than did those without this symptom (respective percentages: 75% vs. 99% and 69% vs. 94%, P ≤ .002). Osmophobia and odor triggered headache were associated with a mild decrease in self-reported olfactory acuity. CONCLUSION: Odor-related disturbances were common symptoms of the 113 migraineurs, with nearly all reporting osmophobia. Perfume odor was the most common trigger for the migraine. The reported symptoms did not differ between patients with and without auras. Patients who experienced IOH appeared to fundamentally differ from those who did not experience IOH in terms of the incidence of osmophobia and odor-triggered crisis. Subjects who reported experiencing osmophobia and odor-triggered headache reported having worse olfactory acuity.

Olfactory Dysfunction in Frontline Health Care Professionals During COVID-19 Pandemic in Brazil.

Upper respiratory viral infections can decrease the sense of smell either by inflammatory restriction of nasal airflow that carries the odorant molecules or through interference in olfactory sensory neuron function. During the coronavirus disease 2019 (COVID-19) pandemic, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), worldwide reports of severe smell loss (anosmia/hyposmia) revealed a different type of olfactory dysfunction associated with respiratory virus infection. Since self-reported perception of smell is subjective and SARS-CoV-2 exposure is variable in the general population, we aimed to study a population that would be more homogeneously exposed to the virus. Here, we investigated the prevalence of olfactory loss in frontline health professionals diagnosed with COVID-19 in Brazil, one of the major epicenters of the disease. We also analyzed the rate of olfactory function recovery and the particular characteristics of olfactory deficit in this population. A widely disclosed cross-sectional online survey directed to health care workers was developed by a group of researchers to collect data concerning demographic information, general symptoms, otolaryngological symptoms, comorbidities, and COVID-19 test results. Of the 1,376 health professionals who completed the questionnaire, 795 (57.8%) were working directly with COVID-19 patients, either in intensive care units, emergency rooms, wards, outpatient clinics, or other areas. Five-hundred forty-one (39.3%) participants tested positive for SARS-CoV-2, and 509 (37%) were not tested. Prevalence of olfactory dysfunction in COVID-19-positive subjects was 83.9% (454 of 541) compared to 12.9% (42 of 326) of those who tested negative and to 14.9% (76 of 509) of those not tested. Olfactory dysfunction incidence was higher in those working in wards, emergency rooms, and intensive care units compared to professionals in outpatient clinics. In general, remission from olfactory symptoms was frequent by the time of responses. Taste disturbances were present in 74.1% of infected participants and were significantly associated with hyposmia. In conclusion, olfactory dysfunction is highly correlated with exposure to SARS-CoV-2 in health care professionals, and remission rates up to 2 weeks are high.

Relationship of socioeconomic status to olfactory function.

Socioeconomic status can significantly impact health. To what degree education and other socioeconomic factors influence the chemical sense of olfaction is not clear. Most studies that have assessed such influences come from countries lacking large disparities in education and income and generally view such measures as nuisance variables to be controlled for statistically. In this study, we evaluated the influences of education and income on odor identification in a diverse sample of subjects from Brazil, a society where large disparities in both income and education are present. The 40-item University of Pennsylvania Smell Identification Test (UPSIT) was administered to 1572 healthy Brazilian citizens with no self-reported olfactory or gustatory deficits and for whom detailed socioeconomic and educational status data were obtained. Univariate and multivariate models were employed to examine the influence of socioeconomic status on the test scores. After controlling for age, sex, ethnicity, and smoking behavior, income and educational level were positively and independently related to the olfactory test scores (respective ps < 0.001 & 0.01). Both linear and quadratic functions described the relationship between the UPSIT scores and the levels of education and socioeconomic status. Individuals of lower socioeconomic status performed significantly worse than those of higher socioeconomic status on 20 of the 40 odorant items. This study demonstrates socioeconomic status is significantly associated with influence the ability to identify odors. The degree to which this reflects differential exposures to xenobiotic agents, cultural differences, familiarity with odors or their names, cognitive development, or other factors requires further investigation.

Reducing the exposure of the tonsillar fossa does not impact postoperative pain levels in children undergoing tonsillectomy: A double-blind randomized controlled trial.

BACKGROUND: It is not established whether reducing the exposure of the tonsillar fossa would be an effective strategy for postoperative pain relief among the pediatric population submitted to tonsillectomy. We assessed the impact of closing this region using absorbable sutures on pain, on the resumption of normal diet and on the healing process until seven days after surgery. METHODS: Randomized, double-blind, controlled trial comparing postoperative pain in 132 children between the ages of 5 and 12 years undergoing tonsillectomy having bilateral closure, unilateral closure or non-closure of the tonsillar fossa. RESULTS: No differences in pain levels were reported both at discharge and on postoperative day 7. The day of resumption of normal diet was similar in all patients. Less granuloma and edema of the uvula were noted in patients with non-closure of the tonsillar fossa. CONCLUSION: These results showed that reducing the exposure of the tonsillar fossa after the removal of the palatine tonsils was not an effective method for postoperative pain relief in children. Moreover, its closure was associated with slower healing.

Cross-Cultural Adaptation and Validation of SNOT-20 in Portuguese.

Introduction. Chronic rhinosinusitis is a highly prevalent disease, so it is necessary to create valid instruments to assess the quality of life of these patients. The SNOT-20 questionnaire was developed for this purpose as a specific test to evaluate the quality of life related to chronic rhinosinusitis. It was validated in the English language, and it has been used in most studies on this subject. Currently, there is no validated instrument for assessing this disease in Portuguese. Objective. Cross-cultural adaptation and validation of SNOT-20 in Portuguese. Patients and Methods. The SNOT-20 questionnaire underwent a meticulous process of cross-cultural adaptation and was evaluated by assessing its sensitivity, reliability, and validity. Results. The process resulted in an intelligible version of the questionnaire, the SNOT-20p. Internal consistency (Cronbach's alpha = 0.91, P < .001), reliability testing-retesting (r = 0.994, P < .001), content validity, validity of discrimination of patients without chronic rhinosinusitis (U = 44, P < .0001) and assessment of sensitivity to change (SRM = 1.53 and 1.09) were evaluated. Conclusion. We conducted a successful process of cross-cultural adaptation and validation of the SNOT-20 questionnaire into Portuguese.