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.

Development of normative data for the Brazilian adaptation of the University of Pennsylvania Smell Identification Test.

It is well established that olfactory dysfunction has significant implications for safety, nutrition, and quality of life. The more reliable standardized tests of olfactory function, such as the University of Pennsylvania Smell Identification Test (UPSIT), assess odor identification ability. Unfortunately, cultural factors can influence such tests, as a number of odors are not universally recognized. In this study, a Portuguese language version of the UPSIT was administered to an age- and sex-stratified prospective sample of 1820 Brazilian subjects. Normative data were developed for a subset of 1578 subjects who reported having no difficulties smelling or tasting. Individuals with a history of head trauma or, in the case of those over the age of 64 years, Mini-Mental State Examination Scores <24, were excluded from analysis. As in other populations, the test scores were significantly influenced by age and sex. The median overall difference between the North American and Brazilian UPSIT scores was 2.2 points for men and 0.8 points for women, although subtle age-related differences were also apparent. This research represents that largest clinical study of olfaction ever performed in South America. Correction factors based upon age and sex are provided to allow for direct comparisons of Brazilian test scores to those based upon North American norms.

Lateral sphenoid sinus recess cerebrospinal fluid leak: a case series.

The lateral recess of the sphenoid sinus is one of the most common sites of meningocele and spontaneous cerebrospinal fluid (CSF) leak. Despite the availability of several techniques for closure of skull base defects occurring in this location, recurrence still poses a major challenge. This report reviews the experience of surgical repair of lateral sphenoid sinus recess CSF leak at a tertiary referral center and provides a brief discussion of this rare lesion. Nine surgeries were performed for six cases of spontaneous lateral sphenoid sinus recess CSF leak (two revisions and one repair of a new defect). Two patients presented with intracranial hypertension (ICH) and four with meningocele or meningoencephalocele. The transpterygoid approach was used in two procedures. A multilayer graft was used in seven cases and a nasoseptal flap in two. Three patients received lumbar or ventricular shunts, and one received acetazolamide for ICH management. Two minor complications were recorded, and the overall surgical success rate was 78 %. We conclude that nasoseptal flaps are a valid option for repair of recurrent CSF leaks, particularly in the lateral sphenoid sinus recess. Furthermore, identification and correction of ICH plays an essential role in the success of treatment in this patient population.

Prevalence and Magnitude of Olfactory Dysfunction in Allergic Rhinitis.

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.

Effect of drug therapies on self-reported chemosensory outcomes after COVID-19.

Objective: The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection on self-reported alterations in taste and/or smell function. Methods: Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019 (post-COVID-19) chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the disease. The dependent measure-self-reported total recovery of chemosensory symptoms-was subjected to stepwise logistic regression. Independent predictors included demographic and clinical variables, in addition to specific medications used to mitigate disease symptoms (i.e., systemic corticosteroids, oseltamivir, vitamin C, ibuprofen, hydroxychloroquine, azithromycin, ivermectin, nitazoxanide, anticoagulants, and zinc). Results: The median time between COVID-19 symptom onset and the interviews was 81 days (interquartile range: 60-104). Of the 714 subjects, 249 (34.9%) reported total recovery of their chemosensory function; 437 (61.2%) had at least one treatment since the beginning of the disease. Women and those with more comorbidities had undergone more treatments. The recovery rates of the treated and nontreated groups did not differ significantly. Nonetheless, respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell recovery. Those who took oral zinc were less likely to improve. Conclusions: No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal, although nitrazoxide trended in a positive direction. Oral zinc had a negative effect on the reported recovery of these senses.

High prevalence of olfactory dysfunction detected in treatment-naive patients with head and neck cancer.

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.

Outcomes of Endoscopic Sinus Surgery for Chronic Rhinosinusitis in Adults with Primary Ciliary Dyskinesia.

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.

Post-acute sequelae of SARS-CoV-2 associates with physical inactivity in a cohort of COVID-19 survivors.

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.

Chemosensory Dysfunction 3-Months After COVID-19, Medications and Factors Associated with Complete Recovery.

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.

Adaptation of the Pediatric Smell WheelTM to evaluate olfactory function in Brazilian children.

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).

Biopsy of the olfactory epithelium from the superior nasal septum: is it possible to obtain neurons without damaging olfaction?

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.

Clinical, sociodemographic and environmental factors impact post-COVID-19 syndrome.

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.

Sinonasal inverted papilloma: rate of recurrence and malignant transformation in 44 operated patients.

INTRODUCTION: Although sinonasal inverted papillomas are benign lesions, they are locally aggressive and have a potential malignant transformation ranging from 5% to 15%, with a high recurrence rate. OBJECTIVE: The aim of this article is to describe the rate of recurrence and malignant transformation in patients with a diagnosis of inverted papilloma who underwent surgery in a tertiary hospital in São Paulo. METHODS: We performed a retrospective analysis of patients diagnosed with sinonasal papilloma who had undergone surgery in a tertiary hospital in São Paulo, between August 1998 and August 2017. A patient chart review was conducted to assess data of patients' demographics, tumors characteristics, follow-up appointments, recurrence and malignancy. Inverted papillomas were analyzed and classified under the Krouse staging system. RESULTS: A total of 69 surgeries were performed in patients with diagnosis of sinonasal papilloma. Inverted papilloma was the most prevalent subtype (49 cases ‒ 80.33%), followed by exophytic papilloma (6 cases ‒ 9.84%) and by oncocytic papilloma (6 cases - 9.84%). The recurrence rate was 34.09% for inverted papilloma (15/44) and the mean time of recurrence was 24.6 months. Malignant transformation occurred in 6 patients (13.64%). Three of these patients presented carcinoma in the first surgery and three patients developed carcinoma during the follow-up. CONCLUSION: The high recurrence rate and malignancy potential allow us to consider inverted papillomas as aggressive tumors. In a tertiary hospital in São Paulo the recurrence rate the mean time to recurrence is 24.6 months. The recurrence after 10 years implies was 34.09% and the need for long-term follow up. It is possible that the high recurrence rate and the high malignant transformation rate we found are due to the large number of tumors discovered at an advanced stage (most of them staged T3 and T4), secondary to poor access to health system, in developing countries.

Prospective evaluation of clarithromycin in recurrent chronic rhinosinusitis with nasal polyps.

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.

Chemosensory Dysfunction in COVID-19: Prevalences, Recovery Rates, and Clinical Associations on a Large Brazilian Sample.

OBJECTIVE: Our study aimed to measure the percentage of reported olfactory or taste losses and their severity, recovery time, and association with other features in a large cohort of patients with COVID-19. STUDY DESIGN: Prospective survey. SETTING: Quaternary medical center and online survey. METHODS: The perceived chemosensory capacities of 655 patients with confirmed COVID-19 were assessed with 11-point category rating scales (0, no function; 10, normal function). Patients were contacted in hospital, by phone calls, or by internet regarding their ability to smell or taste, and 143 were interviewed by phone 1 to 4 months later to assess the recovery of their chemosensory abilities. RESULTS: The prevalence of self-reported olfactory, general taste, and taste quality-specific disturbances (sweet, sour, bitter, and salty) in the patients with COVID-19 were 82.4% (95% CI, 79.5%-85.3%), 76.2% (95% CI, 72.9%-79.4%), and 52.2% (95% CI, 48.3%-56.1%), respectively. The majority reported anosmia (42.9%). The presence of chemosensory symptoms was not associated with COVID-19 severity. At a median time >2 months after the onset of symptoms, rates of total and partial olfaction recovery were 53.8% and 44.7%, while complete or partial return to previous taste function was 68.3% and 27.6%. Less than 5% of the patients reported no chemosensory function improvement at all. CONCLUSION: The prevalence of self-reported chemosensory dysfunction is high among patients with COVID-19. Almost all patients seem to recover a significant part of their smell and taste abilities in the first 4 months after the onset of symptoms.