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BACKGROUND: Although allergic rhinitis (AR) can negatively impact the ability to smell, the degree to which this occurs is not clear and prevalence estimates vary among studies. This study had 4 main objectives: (1) To estimate the prevalence and the degree of olfactory dysfunction in AR patients; (2) To compare olfactory perception between AR patients with different persistence and severity of symptoms and determine if olfactory testing may aid in differentiating among Allergic Rhinitis and its Impact on Asthma (ARIA) groups; (3) To determine whether allergic reactions to different allergens differentially impact olfactory function, and (4) Verify possible changes in the olfactory epithelium (OE) caused by AR. METHODS: One hundred thirty-three patients with AR and one hundred controls were tested. The main outcome was the score in University of Pennsylvania Smell Identification Test (UPSIT®). The OE was examined using immunofluorescence markers for neuronal activity, apoptosis, oxidative stress, signal transduction, eosinophils, and epithelial thickness. RESULTS: Prevalence of olfactory dysfunction in the AR patients was higher (AR: 42.9% vs controls: 9%, P < .001). No difference was found either between intermittent and persistent disease cases (P = .58) or between cases with mild and those with moderate/severe symptomatology (P = .33). Lower olfactory capacity was not associated with the reaction to more (P = .48) or diverse types of allergens (Ps > .05). Although not significant, patients with AR had a greater amount of eosinophilia and a lower amount of cAMP (cyclic adenosine monophosphate) in the OE. CONCLUSION: The study highlights a higher prevalence of olfactory dysfunction in AR patients compared to controls, but olfactory testing may not effectively differentiate AR severity or allergen sensitivities. Although trends suggest potential pathophysiological changes in the OE of AR patients, further research is needed to validate these findings.

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Abstract Introduction Primary ciliary dyskinesia (PCD) is a rare inherited disease associated with impairment of mucociliary transport and, consequently, with a high incidence of chronic rhinosinusitis. For patients with chronic rhinosinusitis who remain symptomatic despite medical treatment, endoscopic sinus surgery is a safe and effective therapeutic option. However, to date, no studies have been found evaluating the effect of surgery on the quality of life associated with the effect on olfaction and nasal endoscopy findings of patients with primary ciliary dyskinesia and chronic rhinosinusitis. Objective To describe the effect of endoscopic sinus surgery on the quality of life, on olfaction, and on nasal endoscopy findings of adults with PCD and chronic rhinosinusitis. Methods Four patients who underwent endoscopic sinus surgery were included. The Sinonasal Outcome Test-22 (SNOT-22) score, the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire, and the Lund-Kennedy score were collected preoperatively and at 3 and 6 months postoperatively. The olfaction as assessed with the University of Pennsylvania Smell Identification Test (UPSIT), which was administered preoperatively and 3 months postoperatively. Results A total of 4 patients with a mean age of 39.3 years old (3 men and 1 woman) completed the study. All patients showed clinically significant improvement in the SNOT-22, NOSE, and Lund-Kennedy scores at 3 months postoperatively, and this improvement was sustained throughout the follow-up period. However, olfaction did not improve after surgery. Conclusion The endoscopic sinus surgery treatment of chronic rhinosinusitis in adults with PCD was associated with improvement in quality of life and endoscopic findings. However, no improvement in olfaction was demonstrated. Studies with a larger number of patients and control groups should help confirm these findings.

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Introduction Primary ciliary dyskinesia (PCD) is a rare inherited disease associated with impairment of mucociliary transport and, consequently, with a high incidence of chronic rhinosinusitis. For patients with chronic rhinosinusitis who remain symptomatic despite medical treatment, endoscopic sinus surgery is a safe and effective therapeutic option. However, to date, no studies have been found evaluating the effect of surgery on the quality of life associated with the effect on olfaction and nasal endoscopy findings of patients with primary ciliary dyskinesia and chronic rhinosinusitis. Objective To describe the effect of endoscopic sinus surgery on the quality of life, on olfaction, and on nasal endoscopy findings of adults with PCD and chronic rhinosinusitis. Methods Four patients who underwent endoscopic sinus surgery were included. The Sinonasal Outcome Test-22 (SNOT-22) score, the Nasal Obstruction Symptom Evaluation (NOSE) questionnaire, and the Lund-Kennedy score were collected preoperatively and at 3 and 6 months postoperatively. The olfaction as assessed with the University of Pennsylvania Smell Identification Test (UPSIT), which was administered preoperatively and 3 months postoperatively. Results A total of 4 patients with a mean age of 39.3 years old (3 men and 1 woman) completed the study. All patients showed clinically significant improvement in the SNOT-22, NOSE, and Lund-Kennedy scores at 3 months postoperatively, and this improvement was sustained throughout the follow-up period. However, olfaction did not improve after surgery. Conclusion The endoscopic sinus surgery treatment of chronic rhinosinusitis in adults with PCD was associated with improvement in quality of life and endoscopic findings. However, no improvement in olfaction was demonstrated. Studies with a larger number of patients and control groups should help confirm these findings.

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BACKGROUND: Previous studies demonstrated the difficulty of patients with Head and Neck Cancer (HNC) in sensing food taste, a function in which olfaction has a significant role. However, neither study employed psychophysical tests or control groups to establish the veracity of such complaints. AIMS/OBJECTIVES: In this study, we quantitatively tested the olfactory function of HNC individuals and compared their function to that of healthy controls. METHODS: Thirty-one HNC naïve treatment patients and thirty-one controls, matched for sex, age, schooling, and smoking, were tested with the University of Pennsylvania Smell Identification Test (UPSIT). RESULTS: The olfactory function was significantly worse among the patients diagnosed with head and neck cancer [UPSIT cancer = 22.9(CI 95%: 20.5-25.4) vs. UPSIT controls = 29.1(CI 95%: 26.9-31.3); p < .001]. Most patients with HNC had olfactory disorders (n = 29, 93.5%). The risk of olfactory loss was higher in the cancer group [OR: 10.5(CI 95%: 2.1-51.9; p = .001)]. CONCLUSION AND SIGNIFICANCE: Olfactory disorders can be detected in more than 90% of patients with head and neck cancer when evaluated using a well-validated olfactory test. Smell disorders may be a potential marker for early diagnosis of HNC.

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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.

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The aim of this study was to determine whether Post-acute Sequelae of SARS-CoV-2 Infection (PASC) are associated with physical inactivity in COVID-19 survivors. This is a cohort study of COVID-19 survivors discharged from a tertiary hospital in Sao Paulo, Brazil. Patients admitted as inpatients due to laboratory-confirmed COVID-19 between March and August 2020 were consecutively invited for a follow-up in-person visit 6 to 11 months after hospitalization. Ten symptoms of PASC were assessed using standardized scales. Physical activity was assessed by questionnaire and participants were classified according to WHO Guidelines. 614 patients were analyzed (age: 56 ± 13 years; 53% male). Frequency of physical inactivity in patients exhibiting none, at least 1, 1-4, and 5 or more symptoms of PASC was 51%, 62%, 58%, and 71%, respectively. Adjusted models showed that patients with one or more persistent PASC symptoms have greater odds of being physically inactive than those without any persistent symptoms (OR: 1.57 [95% CI 1.04-2.39], P = 0.032). Dyspnea (OR: 2.22 [1.50-3.33], P < 0.001), fatigue (OR: 2.01 [1.40-2.90], P < 0.001), insomnia (OR: 1.69 [1.16-2.49], P = 0.007), post-traumatic stress (OR: 1.53 [1.05-2.23], P = 0.028), and severe muscle/joint pain (OR: 1.53 [95% CI 1.08-2.17], P = 0.011) were associated with greater odds of being physically inactive. This study suggests that PASC is associated with physical inactivity, which itself may be considered as a persistent symptom among COVID-19 survivors. This may help in the early identification of patients who could benefit from additional interventions tailored to combat inactivity (even after treatment of PASC), with potential beneficial impacts on overall morbidity/mortality and health systems worldwide.

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OBJECTIVES: To examine the longitudinal prevalence and recovery of olfactory, gustatory, and oral chemesthetic deficits in a sizable cohort of SARS-CoV-2 infected persons using quantitative testing. To determine whether demographic and clinical factors, mainly the medications used after the COVID-19 diagnosis, influence the test measures. METHODS: Prospective cohort in a hospital with primary, secondary, tertiary, and quaternary care. Patients with confirmed COVID-19 were tested during the acute infection phase (within 15 days of initial symptom, n = 187) and one (n = 113) and 3 months later (n = 73). The University of Pennsylvania Smell Identification Test, the Global Gustatory Test, and a novel test for chemesthesis were administered at all visits. RESULTS: During the acute phase, 93% were anosmic or microsmic and 29.4% were hypogeusic. No one was ageusic. A deficit in oral chemesthesis was present in 13.4%. By 3 months, taste and chemesthesis had largely recovered, however, some degree of olfactory dysfunction remained in 54.8%. Remarkably, patients who had been treated with anticoagulants tended to have more olfactory improvement. Recovery was greater in men than in women, but was unrelated to disease severity, smoking behavior, or the use of various medications prior to, or during, COVID-19 infection. CONCLUSIONS: When using quantitative testing, olfactory disturbances were found in nearly all SARS-CoV-2 infected patients during the acute infection phase. Taste or chemesthetic deficits were low. Olfactory impairment persisted to some degree in over half of the patients at the 3-month follow-up evaluation, being more common in women and less common in those who had been treated earlier with anticoagulants. LEVEL OF EVIDENCE: 3.

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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.

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Abstract Objective: Olfaction influences nutrition, safety, and the cognitive development of children. Presently there are few olfactory tests for children, and normative reference values are generally lacking. In this study, we validate the Pediatric Smell WheelTM (PSW) to evaluate olfactory function in Brazilian children. Methods: We modified and validated the PSW, a test developed in the United States, for administration in Brazil, and established normative data for Brazilian children. The validation process consisted of five phases. First, we identified odorants familiar to Brazilian children. Second, we established the test-retest reliability of the Brazilian PSW test that employed these odorants. Third, we compared the test scores of healthy children to those microsmic from adenoid hypertrophy. Fourth, we examined the test's ability to detect improvement in olfactory function before and after adenoidectomy. Finally, we determined a normative 10th percentile cut point for defining microsmia in a sample of 169 healthy Brazilian children between 5 and 12 years of age. Results: Eleven odors were identified for inclusion in the test. The test-retest reliability was modest (r = 0.54, p < 0.001), although likely attenuated based on the inclusion of only data from children with normal function. The test clearly differentiated the olfactory function of children with adenoid hypertrophy from that of healthy children and demonstrated the return of function after adenoidectomy. An overall score <7 was found useful in defining hyposmia, although additional age-related cut-points were also defined. Conclusion: A Brazilian version of the PSW was developed and validated and found to be efficacious in detecting smell dysfunction in children ranging in age from 5 to 12 years. Level of evidence: 1b (Diagnosis).

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Abstract Introduction Olfactory epithelium biopsy has been useful for studying diverse otorhinolaryngological and neurological diseases, including the potential to better understand the pathophysiology behind COVID-19 olfactory manifestations. However, the safety and efficacy of the technique for obtaining human olfactory epithelium are still not fully established. Objective This study aimed to determine the safety and efficacy of harvesting olfactory epithelium cells, nerve bundles, and olfactory epithelium proper for morphological analysis from the superior nasal septum. Methods During nasal surgery, 22 individuals without olfactory complaints underwent olfactory epithelium biopsies from the superior nasal septum. The efficacy of obtaining olfactory epithelium, verification of intact olfactory epithelium and the presence of nerve bundles in biopsies were assessed using immunofluorescence. Safety for the olfactory function was tested psychophysically using both unilateral and bilateral tests before and 1 month after the operative procedure. Results Olfactory epithelium was found in 59.1% of the subjects. Of the samples, 50% were of the quality necessary for morphological characterization and 90.9% had nerve bundles. There was no difference in the psychophysical scores obtained in the bilateral olfactory test (University of Pennsylvania Smell Identification Test [UPSIT®]) between means before biopsy: 32.3 vs. postoperative: 32.5, p= 0.81. Also, no significant decrease occurred in unilateral testing (mean unilateral test scores 6 vs. 6.2, p= 0.46). None out of the 56 different odorant identification significantly diminished (p> 0.05). Conclusion The technique depicted for olfactory epithelium biopsy is highly effective in obtaining neuronal olfactory tissue, but it has moderate efficacy in achieving samples useful for morphological analysis. Olfactory sensitivity remained intact.

Resumo Introdução A biópsia do epitélio olfatório tem sido útil para estudar diversas doenças otorrinolaringológicas e neurológicas, incluindo seu potencial para melhor compreender a fisiopatologia por trás das manifestações olfatórias na COVID‐19. No entanto, a segurança e eficácia da técnica de obtenção de epitélio olfatório humano ainda não estão totalmente estabelecidas. Objetivos Este estudo teve como objetivo determinar a segurança e eficácia da coleta de células do epitélio olfatório, feixes nervosos e epitélio olfatório adequados para análise morfológica, no septo nasal superior. Método Durante a cirurgia nasal, 22 indivíduos sem queixas olfatórias foram submetidos a biópsias de epitélio olfatório do septo nasal superior. A eficácia da obtenção de epitélio olfatório, a verificação de epitélio olfatório íntegro e a presença de feixes nervosos nas biópsias foram avaliadas por imunofluorescência. A segurança da função olfatória foi testada psicofisicamente usando testes unilaterais e bilaterais antes e um mês após o procedimento cirúrgico. Resultados Epitélio olfatório foi encontrado em 59,1% dos sujeitos. Das amostras, 50% apresentaram a qualidade necessária para a caracterização morfológica e 90,9% continham feixes nervosos. Não houve diferença nos escores psicofísicos obtidos no teste olfatório bilateral (University of Pennsylvania Smell Identification Test [UPSIT®]) entre as médias antes da biópsia: 32,3 vs. pós‐operatório: 32,5, p = 0,81. Além disso, nenhuma diminuição significante ocorreu no teste unilateral (escore médio do teste unilateral 6 vs. 6,2, p = 0,46). Não houve redução significante na identificação de nenhum dos 56 odorantes diferentes (p > 0,05). Conclusão A técnica descrita para biópsia de epitélio olfatório é altamente eficaz na obtenção de tecido olfatório neuronal, mas tem eficácia moderada na obtenção de amostras adequadas para análise morfológica. A capacidade olfativa permaneceu intacta.

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Background: Sociodemographic and environmental factors are associated with incidence, severity, and mortality of COVID-19. However, little is known about the role of such factors in persisting symptoms among recovering patients. We designed a cohort study of hospitalized COVID-19 survivors to describe persistent symptoms and identify factors associated with post-COVID-19 syndrome. Methods: We included patients hospitalized between March to August 2020 who were alive six months after hospitalization. We collected individual and clinical characteristics during hospitalization and at follow-up assessed ten symptoms with standardized scales, 19 yes/no symptoms, a functional status and a quality-of-life scale and performed four clinical tests. We examined individual exposure to greenspace and air pollution and considered neighbourhood´s population density and socioeconomic conditions as contextual factors in multilevel regression analysis. Results: We included 749 patients with a median follow-up of 200 (IQR = 185-235) days, and 618 (83%) had at least one of the ten symptoms measured with scales. Pain (41%), fatigue (38%) and posttraumatic stress disorder (35%) were the most frequent. COVID-19 severity, comorbidities, BMI, female sex, younger age, and low socioeconomic position were associated with different symptoms. Exposure to ambient air pollution was associated with higher dyspnoea and fatigue scores and lower functional status. Conclusions: We identified a high frequency of persistent symptoms among COVID-19 survivors that were associated with clinical, sociodemographic, and environmental variables. These findings indicate that most patients recovering from COVID-19 will need post-discharge care, and an additional burden to health care systems, especially in LMICs, should be expected.

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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.

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OBJECTIVE: Olfaction influences nutrition, safety, and the cognitive development of children. Presently there are few olfactory tests for children, and normative reference values are generally lacking. In this study, we validate the Pediatric Smell WheelTM (PSW) to evaluate olfactory function in Brazilian children. METHODS: We modified and validated the PSW, a test developed in the United States, for administration in Brazil, and established normative data for Brazilian children. The validation process consisted of five phases. First, we identified odorants familiar to Brazilian children. Second, we established the test-retest reliability of the Brazilian PSW test that employed these odorants. Third, we compared the test scores of healthy children to those microsmic from adenoid hypertrophy. Fourth, we examined the test's ability to detect improvement in olfactory function before and after adenoidectomy. Finally, we determined a normative 10th percentile cut point for defining microsmia in a sample of 169 healthy Brazilian children between 5 and 12 years of age. RESULTS: Eleven odors were identified for inclusion in the test. The test-retest reliability was modest (r = 0.54, p < 0.001), although likely attenuated based on the inclusion of only data from children with normal function. The test clearly differentiated the olfactory function of children with adenoid hypertrophy from that of healthy children and demonstrated the return of function after adenoidectomy. An overall score <7 was found useful in defining hyposmia, although additional age-related cut-points were also defined. CONCLUSION: A Brazilian version of the PSW was developed and validated and found to be efficacious in detecting smell dysfunction in children ranging in age from 5 to 12 years. LEVEL OF EVIDENCE: 1b (Diagnosis).

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INTRODUCTION: Olfactory epithelium biopsy has been useful for studying diverse otorhinolaryngological and neurological diseases, including the potential to better understand the pathophysiology behind COVID-19 olfactory manifestations. However, the safety and efficacy of the technique for obtaining human olfactory epithelium are still not fully established. OBJECTIVE: This study aimed to determine the safety and efficacy of harvesting olfactory epithelium cells, nerve bundles, and olfactory epithelium proper for morphological analysis from the superior nasal septum. METHODS: During nasal surgery, 22 individuals without olfactory complaints underwent olfactory epithelium biopsies from the superior nasal septum. The efficacy of obtaining olfactory epithelium, verification of intact olfactory epithelium and the presence of nerve bundles in biopsies were assessed using immunofluorescence. Safety for the olfactory function was tested psychophysically using both unilateral and bilateral tests before and 1 month after the operative procedure. RESULTS: Olfactory epithelium was found in 59.1% of the subjects. Of the samples, 50% were of the quality necessary for morphological characterization and 90.9% had nerve bundles. There was no difference in the psychophysical scores obtained in the bilateral olfactory test (University of Pennsylvania Smell Identification Test [UPSIT®]) between means before biopsy: 32.3 vs. postoperative: 32.5, p = 0.81. Also, no significant decrease occurred in unilateral testing (mean unilateral test scores 6 vs. 6.2, p = 0.46). None out of the 56 different odorant identification significantly diminished (p > 0.05). CONCLUSION: The technique depicted for olfactory epithelium biopsy is highly effective in obtaining neuronal olfactory tissue, but it has moderate efficacy in achieving samples useful for morphological analysis. Olfactory sensitivity remained intact.

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Introduction Intra and postoperative bleeding are the most frequent and feared complications in adenotonsillectomy (AT). Tranexamic acid (TXA), which is known for its antifibrinolytic effects, has a proven benefit in reducing bleeding in hemorrhagic trauma and cardiac surgery; however, the effectiveness and timing of its application in AT have not yet been established. Objectives We aimed to evaluate the efficacy of TXA in controlling bleeding during and after AT and assess its possible adverse effects in children. Methods The present randomized, controlled, double-blind clinical trial included 63 children aged 2 to 12 years. They were randomly assigned to receive either intravenous TXA (10 mg/kg) or placebo 10 minutes before surgery. The volume of intraoperative bleeding, presence of postoperative bleeding, and adverse effects during and 8 hours after the surgery were assessed. Results No difference in bleeding volume was noted between the 2 groups (mean, 122.7 ml in the TXA group versus 115.5 ml in the placebo group, p = 0.36). No intraoperative or postoperative adverse effects were noted because of TXA use. Furthermore, no primary or secondary postoperative bleeding was observed in any of the participants. Conclusion In our pediatric sample, TXA (10 mg/kg) administration before AT was safely used, without any adverse effects. It did not reduce the bleeding volume in children during this type of surgery. Future studies should assess the use of higher doses of TXA and its administration at other time points before or during surgery.

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INTRODUCTION: COVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales (often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity. METHODS AND ANALYSES: We will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1-2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6-9 months and 12-15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics. ETHICS AND DISSEMINATION: All components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples. TRIAL REGISTRATION NUMBER: RBR-8z7v5wc; Pre-results.

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Abstract Introduction The antiinflammatory effects of macrolides, especially clarithromycin, have been described in patients with chronic rhinosinusitis without polyps and also other chronic inflammatory airway diseases. There is no consensus in the literature regarding the effectiveness of clarithromycin in patients with chronic rhinosinusitis with sinonasal polyposis and the national literature does not report any prospective studies on the efficacy of clarithromycin in chronic rhinosinusitis in our population. Objective To evaluate the effect of clarithromycin in the adjunctive treatment of recurrent chronic rhinosinusitis with sinonasal polyposis refractory to clinical and surgical treatment. Methods Open prospective study with 52 patients with chronic rhinosinusitis and recurrent sinonasal polyposis. All subjects received nasal lavage with 20 mL 0.9% SS and fluticasone nasal spray, 200 mcg / day, 12/12 h for 12 weeks; and clarithromycin 250 mg 8/8 h for 2 weeks and, thereafter, 12/12 h for 10 weeks. The patients were assessed by SNOT 20, NOSE and Lund-Kennedy scales before, immediately after treatment and 12 weeks after treatment. The patients were also evaluated before treatment with paranasal cavity computed tomography (Lund-Mackay) and serum IgG, IgM, IgA, IgE and eosinophil levels. The outcomes evaluated were: SNOT-20, NOSE and Lund-Kennedy. Results Most patients were women, aged 47 (15) years (median / interquartile range), and 61.5% (32/52) had asthma. All patients completed the follow-up after 12 weeks and 42.3% (22/52) after 24 weeks. Treatment resulted in a quantitative decrease in the SNOT-20 [2.3 (1.6) vs. 1.4 (1.6); Δ = −0.9 (1.1); p < 0.01]; NOSE [65 (64) vs. 20 (63); Δ = −28 (38), p < 0.01] and Lund-Kennedy [11 (05) vs. 07 (05); Δ = −2 (05); p < 0.01] scores. SNOT-20 showed a qualitative improvement (>0.8) in 54% (28/52, p < 0.04) of patients, a group that showed lower IgE level [108 (147) vs. 289 (355), p < 0.01]. The group of patients who completed follow-up 12 weeks after the end of treatment (n = 22) showed no worsening of outcomes. Conclusion Long-term adjuvant use of low-dose clarithromycin for chronic rhinosinusitis patients with recurrent sinonasal polyposis refractory to clinical and surgical treatment has resulted in improved quality of life and nasal endoscopy findings, especially in patients with normal IgE levels. This improvement persisted in the patient group evaluated 12 weeks after the end of the treatment.

Resumo Introdução Os efeitos anti-inflamatórios dos macrolídeos são reconhecidos, principalmente da claritromicina para os pacientes com rinossinusite crônica sem pólipos e outras doenças inflamatórias crônicas das vias aéreas em outras populações. Não existe consenso na literatura quanto a sua prescrição para os pacientes de rinossinusite crônica com polipose nasossinusal e a literatura nacional não dispõe de estudos prospectivos sobre a eficácia da claritromicina na rinossinusite crônica em nossa população. Objetivo Avaliar o efeito da claritromicina no tratamento adjuvante da rinossinusite crônica recorrente com polipose nasossinusal refratária ao tratamento clínico e cirúrgico. Método Estudo prospectivo aberto, com 52 pacientes, portadores de rinossinusite crônica com polipose nasossinusal recorrente. Todos os indivíduos receberam lavagem nasal com SF 0,9% 20 mL e fluticasona spray nasal, 200 mcg/dia, 12/12 horas por 12 semanas; e claritromicina 250 mg, de 8/8 horas, por 2 semanas e posteriormente 12/12 horas, por 10 semanas. Os pacientes foram avaliados através do SNOT 20, do NOSE e Lund-Kennedy antes, pós-tratamento imediato e 12 semanas após o tratamento. Os pacientes também foram avaliados antes do tratamento por tomografia computadorizada das cavidades paranasais (Lund-Mackay) e dosagem sérica de IgG, IgM, IgA, IgE e eosinófilos. Os desfechos avaliados foram: SNOT-20, NOSE e Lund-Kennedy. Resultados A maioria dos pacientes era mulher, idade de 47 (15) anos (mediana/intervalo interquartílico) e 61,5% (32/52) portadores de asma. Todos os pacientes completaram o seguimento após 12 semanas e 42,3% (22/52) após 24 semanas. O tratamento resultou em uma diminuição quantitativa do SNOT-20 [2,3 (1,6) vs. 1,4 (1,6); Δ = -0,9 (1,1); p< 0,01]; do NOSE [65 (64) vs. 20 (63); Δ = -28 (38), p< 0,01] e do Lund-Kennedy [11 (05) vs. 07 (05); Δ = -2 (05); p< 0,01]. O SNOT-20 mostrou uma melhoria qualitativa (> 0,8) em 54% (28/52, p< 0,04) dos pacientes, grupo que evidenciou menor nível de IgE [108 (147) vs. 289 (355), p< 0,01]. O grupo de pacientes que completou o seguimento 12 semanas após o término do tratamento (n = 22) não mostrou uma pioria dos desfechos. Conclusão O uso prolongado adjuvante da claritromicina em baixas doses para pacientes com rinossinusite crônica com polipose nasossinusal recorrente refratária ao tratamento clínico e cirúrgico resultou em melhoria na qualidade de vida e endoscopia nasal, principalmente em pacientes com níveis de IgE normal. Essa melhoria se sustentou no grupo de pacientes avaliado 12 semanas após o término do tratamento.

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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.