Online survey about oral manifestations of COVID-19

Introduction: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 (Coronavirus type 2 causing severe acute respiratory syndrome) presents systemic manifestations such as fever, anosmia, cough, sore throat and headache, dyspnea, tiredness, malaise, diarrhea. There are reports of developing dysgeusia, xerostomia, and vesiculobullous lesions as oral manifestations related to COVID-19. Objective(s): To identify the most prevalent oral manifestations associated with COVID-19 in a group of Paraguayans. Material(s) and Method(s): An electronic survey was used from January to March 2022. Data were presented as frequencies and percentages and analyzed using the chi2 test. Statistical analysis was performed with R software version 4.0.3. Result(s): The sample consisted of 478 people, most female from 15 to 34 years old. 65.48% stated that they had had at least one oral symptom or sign during COVID-19. The loss in the sensation of bitter tastes (34.31%), the alteration of the taste of food (32.43%), and the loss of sweetness (32.01%) were the most prevalent symptoms. In addition, it was found that among the people who developed moderate to severe COVID-19, there was a more significant number (77.78%) of oral manifestations compared to the participants who developed it mildly (63.92%) (chi2;p= 0.044). Conclusion(s): More than half of the respondents presented oral manifestations, more frequent in those who developed moderate to severe COVID-19. Results will serve as a basis for future research and thus strengthen the surveillance of this disease.

COVID-19-Related Long-Term Taste Impairment: Symptom Length, Related Taste, Smell Disturbances, and Sample Characteristics.

INTRODUCTION:  The COVID-19 infection triggered in some patients a prolonged reduction in the perception of both gustatory and olfactory senses (ageusia and anosmia). These symptoms could be manifested during the first days after the contagion, acting as predictors of COVID-19 infection, and additionally, they could be the only symptoms manifested at all. Clinical resolution of anosmia and ageusia was expected to occur within a few weeks, yet in some cases, patients began to demonstrate COVID-19-related long-term taste impairment (CRLTTI), a condition that can persist for longer than two months, contradicting initial evidence.  Objectives: The authors' aimed to describe the characteristics of the sample of 31 participants with COVID-19-related long-term taste impairment, and their capacity to quantify taste and rate their smell perception.  Material and Methods: Participants were submitted to a taste evaluation of four hyper-concentrated tastes perceived by the tongue (0-10), self-reported their smell (0-10), and answered a semi-structured questionnaire.  Results: Different tastes seemed to be affected differently by COVID-19, despite the lack of statistical relevance observed in this study. Dysgeusia was only expressed in bitter, sweet, and acidic tastes. The mean age observed was 40.2 (SD 12.06) years, with women representing 71% of the sample. Taste impairment persisted for an average period of 10.8 months (SD 5.7). Self-reported smell impairment was reported by the majority of participants with taste impairment. Non-vaccinated people represented 80.6% of the sample.  Conclusions: COVID-19 infection could trigger taste and smell disturbances that lasted as long as 24 months. CRLTTI seems not to affect the four main taste perceptions (hyper-concentrated) equally. Women represented the majority of the sample, with an average age of 40 years (SD 12.06). Previous diseases, medication use, and behavioral aspects seem not to be linked to CRLTTI development.

Construction of Tibetan Medicine Prescription Database for Treating "Gnyan-rims" and Analysis of Their Medication Law Based on Python Language.

Objective: To construct the database of Tibetan medicine prescriptions for "Gnyan-rims" disease,and to explore the invisible medication law of Tibetan medicine in the treatment of "Gnyan-rims" disease,such as prescription compatibility and combination of drug properties. Method: The prescriptions for treating "Gnyan-rims" were retrieved from four Tibetan medical literatures such as The Four Medical Tantras,Kong-sprul-zin-tig, Phyag-rdor-gso-rig-phyogs-bsgrigs and Sman-sbyor-lag-len-phyogs-bsgrigs, and the database was constructed under Python code,and the Apriori algorithm and the vector structure model of taste property flavor transformation were used for analysis. Result:According to the characteristics of Tibetan medicine prescription data,with six fields of prescription name,formula,dosage,efficacy,source and original text as the core,a Tibetan medicine treatment "Gnyan-rims" prescription database with functions of cleaning, searching and exporting was established. A total of 7 602 prescriptions were included in the database,among which 598 prescriptions had therapeutic effects of "Gnyan" and "Rims". The results of compatibility analysis showed that Shexiang,Hezi,Honghua,Mukuer Moyao,Tiebangchui,Tianzhuhuang and Bangga were the most frequently used drugs,while the correlation degrees of Shexiang-Mukuer Moyao,Honghua-Tianzhuhuang,Shexiang-Hezi and Shexiang-Tiebangchui were the strongest,and all the drug composition of Wuwei Shexiang pills appeared in the top ten correlations. According to the property analysis of 40 prescriptions containing high-frequency drugs,19 prescriptions were found to have excessive bitter taste,followed by 9 prescriptions such as Sanchen powders with excessive sweetish taste,and the ratios of sweetish and bitter tastes in six tastes were >35%. The total of sweetish and bitter prescriptions accounted for 70% of the total prescriptions. Among the three flavors,the bitter flavor was the most abundant. The cool effect,dull effect and heavy effect were prominent among the seventeen effects. Conclusion: The prescription database of Tibetan medicine for "Gnyan-rims" can promote the high-quality development of research on prevention and treatment of plague with ethnic medicine. Tibetan medicine treatment of "Gnyan-rims" focuses on the composition of Wuwei Shexiang pills,with the property combination of "cool-bitter and sweet-bitter flavor-cool,dull and heavy", which mainly treats diseases such as "heat sharp light-mkhris pa-heat". These studies can provide data basis and theoretical reference for the selection of Tibetan medicine prescription and its composition for treating plague.Copyright © 2021, China Academy of Chinese Medical Sciences Institute of Chinese Materia Medica. All rights reserved.

Human T2R38 Bitter Taste Receptor Expression and COVID-19: From Immunity to Prognosis

Background: Bitter taste-sensing type 2 receptor (T2Rs or TAS2Rs) found on ciliated epithelial cells and solitary chemosensory cells have a role in respiratory tract immuni-ty. T2Rs have shown protection against SARS-CoV-2 by enhancing the innate immune response. The purpose of this review is to outline the current sphere of knowledge re-garding this association. Method(s): A narrative review of the literature was done by searching (T2R38 OR bitter taste receptor) AND (COVID-19 OR SARS-CoV-2) keywords in PubMed and google scholar. Result(s): T2R38, an isoform of T2Rs encoded by the TAS2R38 gene, may have a potential association between phenotypic expression of T2R38 and prognosis of COVID-19. Current studies suggest that due to different genotypes and widespread distributions of T2Rs within the respiratory tract and their role in innate immunity, treatment protocols for COVID-19 and other respiratory diseases may change accordingly. Based on the phenotypic expression of T2R38, it varies in innate immunity and host response to respiratory infection, systemic symptoms and hospitalization. Conclusion(s): This review reveals that patients' innate immune response to SARS-COV-2 could be influenced by T2R38 receptor allelic variations.Copyright © 2023, Avicenna Journal of Medical Biotechnology.

Postmarketing Reporting of Paxlovid-Related Dysgeusia: A Real-World Pharmacovigilance Study.

OBJECTIVE: A novel COVID-19 therapeutic, nirmatrelvir/ritonavir (Paxlovid), is commonly associated with reports of dysgeusia. The Food and Drug Administration Adverse Event Reporting System (FAERS) database was used to determine the real-world reporting of Paxlovid-associated dysgeusia (PAD), identify associated factors, and describe the relative reporting rates of dysgeusia for Paxlovid compared to other COVID-19 therapeutics (OCT), ritonavir alone, and other protease inhibitors (OPI). STUDY DESIGN: Observational retrospective. SETTING: Tertiary academic medical center. METHODS: We collected patient and adverse event characteristics reported in the FAERS database between January 1968 and September 2022. Disproportionality analyses were used to compare the reporting of PAD to dysgeusia reported for OCT, ritonavir, and OPI. RESULTS: 345,229 adverse events were included in the present study. Dysgeusia was a frequently reported Paxlovid-associated adverse event (17.5%) and was associated with nonserious COVID-19 infection (reporting odds ratio [ROR] 1.4; 95% confidence interval [CI] 1.2, 1.7) and female sex (ROR = 1.7; 95% CI 1.6, 1.9). Paxlovid was more likely to be associated with the reporting of dysgeusia compared to OCT (ROR 305.4; 95% CI 164.1, 568.5), ritonavir (ROR 28.0; 95% CI 24.1, 32.7), and OPI (ROR 49.0; 95% CI 42.8, 56.1). CONCLUSION: Dysgeusia is much more likely to be reported by patients receiving Paxlovid than those receiving OCT, ritonavir alone, or OPI. These findings suggest a potential mechanism of dysgeusia that causes distorted taste out of proportion to the background effects of COVID-19 infection and specific to nirmatrelvir. Future studies are needed to determine the underlying pathophysiology and long-term clinical implications for patients who report dysgeusia with Paxlovid.

COVID-19-ASSOCIATED PULMONARY MUCORMYCOSIS PRESENTING AS SPONTANEOUS PNEUMOTHORAX: A RARE PRESENTATION

SESSION TITLE: COVID-19 Case Report Posters 1 SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Mucormycosis is an angio-invasive fungal infection with substantial morbidity and mortality. While diabetes and immune suppression remain well-known risk factors for mucormycosis, COVID-19 is now emerging as its independent predictor. CASE PRESENTATION: A 43-year-old male, with a history of hyperlipidemia and alcoholism, presented to the hospital with complaints of progressive dyspnea on exertion, productive cough, intermittent fever, anorexia, and chest pain over the course of 2 weeks. About 5 weeks prior to the current presentation, he was tested positive for COVID-19 by a polymerase chain reaction (PCR) based test and remained in quarantine at home. He was not vaccinated against COVID-19. He had no known immunosuppressive disease. On initial examination, he was ill-appearing and had a temperature of 101 F, blood pressure 138/83 mmHg, respiratory rate 22/minute, pulse 102/minute, and saturation of 91% on 2 L nasal cannula oxygen. A computerized tomography (CT) scan of the chest revealed small bilateral pneumothorax (2 cm and 5mm) along with extensive ground-glass opacifications in all lobes. In the next 24 hours, the right-sided pneumothorax progressed to tension pneumothorax requiring pigtail pleural drainage catheter placement. The drained pleural fluid had more than 100,000/uL total nucleated cells (91% neutrophils, 2% lymphocytes, and 1% eosinophils) and ultimately cultures grew Rhizopus spp. He was started on intravenous liposomal amphotericin-B infusion (5 mg/kg daily). On hospital discharge, he was switched to oral posaconazole (started with loading 300 mg delayed-release tablet twice a day, followed by 300 mg dosing of delayed-release posaconazole tablets daily) to complete the long term treatment course. DISCUSSION: Most of the reported cases of mucormycosis in COVID-19 were in patients with either diabetes or receiving steroids. This is a rare presentation of COVID-19–associated pulmonary mucormycosis (CAPM) as spontaneous pneumothorax, in the absence of known immunosuppression history. COVID-19 results in a considerable increase in cytokines, particularly interleukin-6 (IL-6), which increase free iron by increasing ferritin levels due to increased synthesis and decreased iron transport. Also, concomitant acidosis increases free iron by reducing the ability of transferrin to chelate iron and this available iron becomes a considerable resource for mucormycosis. [1] Also, Mucorales adheres to and invades endothelial cells by specific recognition of the host receptor glucose-regulator protein 78 (GRP-78). Acidosis associated with severe COVID-19 triggers GRP-78 and fungal ligand spore coating homolog (CotH) protein expression on endothelial cells, both contributing to angioinvasion, hematogenous dissemination, and tissue necrosis. [2] CONCLUSIONS: Mucormycosis can present as spontaneous pneumothorax after recent COVID-19 and clinicians should be aware of rare clinical presentation. Reference #1: Singh AK, Singh R, Joshi SR, et al. Mucormycosis in COVID-19: A systematic review of cases reported worldwide and in India. Diabetes Metab Syndr Clin Res Rev 2021;15:102146. doi:10.1016/j.dsx.2021.05.019 Reference #2: Baldin C, Ibrahim AS. Molecular mechanisms of mucormycosis—The bitter and the sweet. PLOS Pathog 2017;13:e1006408. doi:10.1371/journal.ppat.1006408 DISCLOSURES: No relevant relationships by Faran Ahmad No relevant relationships by AYESHA BATOOL No relevant relationships by Zachary DePew No relevant relationships by Neil Mendoza

Effect of Pumpkin Cultivar on the Selected Quality Parameters of Functional Non-Dairy Frozen Desserts

This study was conducted to investigate the influence of pumpkin cultivar as a fermented semi-product on the selected quality parameters of functional non-dairy frozen desserts, which were prepared using the potentially probiotic strain cultures L. rhamnosus Lock 0900 and L. casei O14. Microbiological status, pH, sugar and carotenoids content, antioxidant activity, color and sensory quality have been checked. Regardless of the pumpkin cultivar used, the lactic acid fermentation of pulps with selected bacterial strains decreased reducing sugar and total sugars content. Improvement in the antioxidant activity was also observed. The impact of the individual sensory attributes on the overall quality was determined. The overall quality of the investigated pumpkin sorbets was positively driven by the sweet taste, pumpkin flavor, smoothness of texture, and negatively driven by acidic flavor, pungent taste, and bitter taste, verified by PCA method. All of the final products achieved high survival of probiotics (higher than 8.4 log CFU/g) and revealed a good sensory quality (overall quality higher than 8 c.u). The treatments with the cultivar “Melon Yellow” of the Cucurbita maxima species, were characterized by significantly higher (p < 0.05) carotenoids content, total sugars and reducing sugars content and antioxidant activity, measured by two methods. It can be concluded that the pumpkin cultivar and strain culture used for the fermentation affect the count of potentially probiotic bacteria in the final products, the composition of bioactive compounds, antioxidant activity and sensory quality of the functional pumpkin frozen desserts.

Gustatory dysfunction in long COVID

Background This study aims to investigate the prevalence and long-term development of gustatory dysfunction (GD) after COVID-19. Methods In the population-based cross-sectional COVIDOM-study, 667 patients above the age of 18 years (mean 48.2) who tested positive for SARSCoV- 2 via PCR-testing on average 9.09 months ago were examined between November 2020 and June 2021. Extensive medical history taking was conducted via questionnaires. Participants were asked to rate their ability to taste before, during and after COVID-19 on a Visual Analogue Scale (VAS) ranging from 0 to 10. Whole mouth gustatory testing with Taste Strips for the qualities sweet, sour, salty, and bitter was performed. Results 60.9 % (406 of 667) participants reported gustatory impairment during their infection. Out of those, 56.9 % perceived this symptom as severe and 13.3 % noticed it as the earliest symptom. At the time of our examination, 36.2 % had a persistent subjective GD, defined as a lower score on the VAS than before COVID-19 (mean difference -0.9 points). This difference was significant (p < 0.001). In the testing, 7.3 % (47 of 667) participants had a GD, defined as the correct identification of less than three out of four Taste Strips. No signifi- cant correlation was found between subjectively persistent and tested GD (p = 0.250). Conclusions SARS-CoV-2 seems to frequently affect the gustatory function in the long term as well, what might have an influence on patients' everyday-life. However, Patients' own perception does not always correspond with psychophysiological testing which might be caused by the common difficulty to differentiate between the chemosensory senses of taste and smell.

HSP90 Modulates T2R Bitter Taste Receptor Nitric Oxide Production and Innate Immune Responses in Human Airway Epithelial Cells and Macrophages

Bitter taste receptors (T2Rs) are G protein-coupled receptors (GPCRs) expressed in various cell types including ciliated airway epithelial cells and macrophages. T2Rs in these two innate immune cell types are activated by bitter products, including those secreted by Pseudomonas aeruginosa, leading to Ca2+-dependent activation of endothelial nitric oxide (NO) synthase (eNOS). NO enhances mucociliary clearance and has direct antibacterial effects in ciliated epithelial cells. NO also increases phagocytosis by macrophages. Using biochemistry and live-cell imaging, we explored the role of heat shock protein 90 (HSP90) in regulating T2R-dependent NO pathways in primary sinonasal epithelial cells, primary monocyte-derived macrophages, and a human bronchiolar cell line (H441). Immunofluorescence showed that H441 cells express eNOS and T2Rs and that the bitter agonist denatonium benzoate activates NO production in a Ca2+- and HSP90-dependent manner in cells grown either as submerged cultures or at the air–liquid interface. In primary sinonasal epithelial cells, we determined that HSP90 inhibition reduces T2R-stimulated NO production and ciliary beating, which likely limits pathogen clearance. In primary monocyte-derived macrophages, we found that HSP-90 is integral to T2R-stimulated NO production and phagocytosis of FITC-labeled Escherichia coli and pHrodo-Staphylococcus aureus. Our study demonstrates that HSP90 serves as an innate immune modulator by regulating NO production downstream of T2R signaling by augmenting eNOS activation without impairing upstream Ca2+ signaling. These findings suggest that HSP90 plays an important role in airway antibacterial innate immunity and may be an important target in airway diseases such as chronic rhinosinusitis, asthma, or cystic fibrosis.

An analysis of TCM disease syndromes of 36 cases of coronavirus disease 2019 (COVID-19) in Kunming, China

Objective: To analyze the distribution characteristics of syndrome of TCM of the patients with COVID-19 in Kunming, China. Methods: To classify and summarize the TCM syndrome types of COVID-19 patients via Cluster analysis combining with tongue image, chest CT and clinical expertise of 36 Covid-19 patients in Kunming. Results: In the 36 cases of Kunming region confirmed COVID-19 patients, 17 cases had fever (47.2%), 18 cases had cough (50%), 16 cases felt bitter taste in the mouth (44.4%), 18 cases felt dry throat (50.0%), 17 cases had poor appetite (47.2%), 15 cases had nausea (41.7%);12 cases had diarrhea (33.3%), 15 cases had insomnia (41.7%);12 cases had chest tightness (33.3%);3 cases had dyspnea (8.3%);6 cases had nasal congestion and running nose (16.7%);15 cases had fatigue (41.7%);6 cases had headache and body pain (16.7%);5 cases had red tongue (13.9%);18 cases had pale red tongue (50%);8 cases had tongue with red edge and tip (22.2%);3 cases had dark red tongue (8.3%);2 cases had cyanosis (5.6%);3 cases had swollen tongue (8.3%);18 cases had dentate tongue (50%);4 cases had yellow tongue coating (11.1%);5 cases had yellow sticky tongue coating (13.9%);12 cases had white sticky tongue coating (33.3%);6 cases had thin white tongue coating (16.7%);2 cases had no tongue coating (5.6%). The chest CT results showed that: There were five cases without lesions. The lesions were located in the upper lobe of one lung in 13 cases located in the lower lobe of one lung in seven cases, located in the upper middle lobe in three cases, located in the lower lobe in five cases, and in the upper middle and lower lobes of double lung in 13 cases. There were 14 cases of Shaoyang syndrome, 17 cases of wet Resistance Tir-juao Syndrome. According to the time of onset, the disease was followed by Shaoyang Syndrome (1 day), the Wet blocked tri-jiao Syndrome (3 days), epidemic poison retention lung syndrome and syndrome of flaring heat in qifen and yingfen (5 days), and dampness-toxicity lung-stagnation syndrome (6 days). Conclusion: The TCM syndromes of COVID-19 in Kunming are mainly the Wet Resistance Tri-Jiao Syndrome and Shaoyang syndrome, followed by dampness-toxicity lung-stagnation syndrome, epidemic poison retention lung and syndrome of flaring heat in qifen and yingfen.

Treatment Protocol for COVID-19 Based on T2R Phenotype.

COVID-19 has become a global pandemic of the highest priority. Multiple treatment protocols have been proposed worldwide with no definitive answer for acure. A prior retrospective study showed association between bitter taste receptor 38 (T2R38) phenotypes and the severity of COVID-19. Based on this, we proposed assessing the different T2R38 phenotypes response towards a targeted treatment protocol. Starting July 2020 till December 2020, we tested subjects for T2R38 phenotypic expression (supertasters, tasters, and nontasters). Subjects who were subsequently infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (diagnosed via PCR) were included. Based on their taster status, supertasters were given dexamethasone for 4 days; tasters were given azithromycin and dexamethasone +/- hydroxychloroquine for 7 days; and nontasters were given azithromycin and dexamethasone for 12 days. Subjects were followed prospectively and their outcomes were documented. Seven hundred forty-seven COVID-19 patients were included, with 184 (24.7%) supertasters, 371 (49.6%) tasters, and192 (25.7%) nontasters. The average duration of symptoms with the treatment protocol was 5 days for supertasters, 8.1 days for tasters, and 16.2 days for nontasters. Only three subjects (0.4%) required hospitalization (3/3 nontasters). Targeted treatment protocol showed significant correlation (p < 0.05) based on patients' T2R38 phenotypic expression. Assessing treatment protocols for COVID-19 patients according to their T2R38 phenotype could provide insight into the inconsistent results obtained from the different studies worldwide. Further study is warranted on the categorization of patients based on their T2R38 phenotype.

Chloroquine: Autophagy inhibitor, antimalarial, bitter taste receptor agonist in fight against COVID-19, a reality check?

The recent SARS-CoV-2 pandemic poses one of the greatest challenges to modern medicine. Therefore, identification of new therapeutic strategies seems essential either based on novel vaccines or drugs or simply repurposing existing drugs. Notably, due to their known safety profile, repurposing of existing drugs is the fastest and highly efficient approach to bring a therapeutic to a clinic for any new indication. One such drug that has been used extensively for decades is chloroquine (CQ, with its derivatives) either for malaria, lupus and rheumatoid arthritis. Accumulating body of evidence from experimental pharmacology suggests that CQ and related analogues also activate certain pathways that can potentially be exploited for therapeutic gain. For example, in the airways, this has opened an attractive avenue for developing novel bitter taste ligands as a new class of bronchodilators for asthma. While CQ and its derivatives have been proposed as a therapy in COVID-19, it remains to be seen whether it really work in the clinic? To this end, our perspective aims to provide a timely yet brief insights on the existing literature on CQ and the controversies surrounding its use in COVID-19. Further, we also highlight some of cell-based mechanism(s) that CQ and its derivatives affect in mediating variety of physiological responses in the cell. We believe, data emanating from the clinical studies and continual understanding of the fundamental mechanisms may potentially help in designing effective therapeutic strategies that meets both efficacy and safety criteria for COVID-19.

Chloroquine and COVID-19: role as a bitter taste receptor agonist?

COVID-19 is a world public health emergency caused by the new coronavirus, SARSCoV-2. Many drugs were repurposed as a treatment for COVID-19 patients including Chloroquine (CQ). CQ is a bitter taste receptor agonist reported to relax the airways suggesting a role in preventing disease severity of COVID-19 patients with asthma.

Does phenotypic expression of bitter taste receptor T2R38 show association with COVID-19 severity?

BACKGROUND: Severe acute respiratory syndrome-associated coronavirus-2 (SARS-CoV-2) has been identified as the pathogen causing the outbreak of coronavirus disease-2019 (COVID-19) commencing in Wuhan, China, in December 2019. Multiple reports have shown subjective loss of taste and smell as an early and hallmark symptom for COVID-19. METHODS: A retrospective study was performed in our clinical practice during July 2020 on patients positive for SARS-CoV-2 via polymerase chain reaction. All patients were categorized into 3 groups (supertasters, tasters, and nontasters) via taste sensitivity to phenylthiocarbamide, thiourea, and sodium benzoate with taste strip testing. The results of the taste strip tests were correlated with clinical course. RESULTS: A total of 100 patients (mean, 51 [range, 24-82] years of age; 44 [44%] women) were assessed. We found that 21 of 100 (21%) were nontasters, 79 of 100 (79%) were tasters, and 0 of 100 (0%) were supertasters (p < 0.001). Twenty-one of 21 (100%) (p < 0.001) of the patients requiring inpatient admission were classified as nontasters. All 79 (100%) (p < 0.001) of the patients who displayed mild to moderate symptoms not requiring admission were classified as tasters. CONCLUSION: Our results show objective data that taste disturbance, specifically global loss of taste, appears to correlate with the clinical course specific to each individual, because 100% of the patients requiring inpatient admission were classified as nontasters.