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.

Upper Airway Mucociliary Clearance is Impaired in Dyspneic COVID-19 Patients.

Covid-19 is transmitted mainly by respiratory droplets and as the upper airway mucosa is the first innate immune barrier, it is crucial to understand the effects of SARS-CoV-2 on this system. In the current study, we aimed to evaluate the nasal mucociliary clearance in patients with SARS-CoV-2 infection and their symptom development. Observational cross-sectional study. The nasal mucociliary clearance (NMC) time was evaluated by the saccharin test and the results were compared between patients with SARS-CoV-2 infection (group 1) and controls (group 2, asymptomatic patients with a negative polymerase chain reaction test). We also compared the NMC time for each specific symptom suffered by participants in group 1 with the NMC time of the control group as well as with the patients in group 1 who were asymptomatic. There was a significant increase in NMC time in group 1 with dyspnea when compared to the control group (p = 0.032) and also when compared to patients who were infected were not dyspneic (p = 0.04). There were no differences in the clearance times when considering other symptoms. COVID-19 patients with dyspnea present with altered nasal mucociliary clearance.

Upper Airway Mucociliary Clearance is Impaired in Dyspneic COVID-19 Patients

Covid-19 is transmitted mainly by respiratory droplets and as the upper airway mucosa is the first innate immune barrier, it is crucial to understand the effects of SARS-CoV-2 on this system. In the current study, we aimed to evaluate the nasal mucociliary clearance in patients with SARS-CoV-2 infection and their symptom development. Observational cross-sectional study. The nasal mucociliary clearance (NMC) time was evaluated by the saccharin test and the results were compared between patients with SARS-CoV-2 infection (group 1) and controls (group 2, asymptomatic patients with a negative polymerase chain reaction test). We also compared the NMC time for each specific symptom suffered by participants in group 1 with the NMC time of the control group as well as with the patients in group 1 who were asymptomatic. There was a significant increase in NMC time in group 1 with dyspnea when compared to the control group (p = 0.032) and also when compared to patients who were infected were not dyspneic (p = 0.04). There were no differences in the clearance times when considering other symptoms. COVID-19 patients with dyspnea present with altered nasal mucociliary clearance.

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.

Impact of SARS-CoV-2 on saliva: TNF-⍺, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM.

OBJECTIVES: Understanding the role of certain salivary components, such as TNF-⍺, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM, in airway defense during the ongoing SARS-CoV-2 pandemic is essential. The salivary immune barrier of patients with COVID-19 may play a role in their prognosis. The present study aims to evaluate the impact of SARS-CoV-2 on saliva composition. METHODS: A longitudinal study was carried out with male and female firefighters aged 24-48 years. The study sample (n = 34) was divided into 3 groups: asymptomatic volunteers with a negative polymerase chain reaction (PCR) test for SARS-CoV-2 (group 1, Control, n = 21); patients with symptoms of COVID-19 of less than 7 days' duration and a diagnosis of SARS-CoV-2 infection by PCR (group 2, COVID-19, n = 13); and recovered patients from group 2 who were free of COVID-19 symptoms for at least 2 months (group 3, post-COVID-19 recovery, n = 13). All groups underwent real-time PCR to detect the presence of SARS-CoV-2, as well as analysis of the salivary concentrations of TNF-⍺, IL-6, IL-10, lactoferrin, lysozyme, IgG, IgA, and IgM by the ELISA method. RESULTS: Lactoferrin concentrations were significantly decreased in the infected group (COVID-19) when compared to those not infected by SARS-CoV-2 (control) (p = 0.032). IgA concentrations were decreased in the COVID-19 and post-COVID-19 groups compared to the control group (p = 0.005 and p = 0.016, respectively). Comparison of the COVID-19 and post-COVID-19 groups also revealed an increase in IgM concentrations during acute SARS-CoV-2 infection (p = 0.010). CONCLUSION: SARS-CoV-2 alters the composition of the salivary immune barrier.

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.

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.

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.