Integrative Systems Immunology Analysis Reveals Elevated Anti-AGTR1 Levels with Accumulating COVID-19 Symptoms (preprint)

The coronavirus disease 2019 (COVID-19) displays a broad spectrum of symptoms, with the underlying reasons for this variability still not fully elucidated. Our study investigates the potential association between specific autoantibodies (AABs), notably those that targeting G protein-coupled receptors (GPCRs) and renin-angiotensin system (RAS) related molecules, and the diverse clinical manifestations of COVID-19, commonly observed in patients with autoimmune conditions, including rheumatic diseases, such as systemic sclerosis. In a cross-sectional analysis, we explored the relationship between AAB levels and the presence of key COVID-19 symptoms. Hierarchical clustering analysis revealed a robust correlation between certain AABs and symptoms such as fever, muscle ache, anosmia, and dysgeusia, which emerged as significant predictors of disease severity. Specifically, AABs against CHRM5 and CXCR3 were strongly linked to fever, while AABs against CHRM5 and BDKRB1 correlated with muscle ache. Anosmia was predominantly associated with AABs against F2R and AGTR1, while dysgeusia was linked to AABs against BDKRB1 and AGTR1. Furthermore, we observed a rise in AAB levels with the accumulation of these symptoms, with the highest levels detected in patients presenting all four predictors. Multinomial regression analysis identified AABs targeting AGTR1 as a key predictor for one or more of these core symptoms. Additionally, our study indicated that anti-AGTR1 antibodies triggered a concentration-dependent degradation of eGC, which could be mitigated by the AGTR1 antagonist Losartan. This suggests a potential mechanistic connection between eGC degradation, the observed COVID-19 symptoms, and rheumatic diseases. In conclusion, our research underscores a substantial correlation between AABs, particularly those against GPCRs and RAS-related molecules, and the severity of COVID-19 symptoms. These findings open avenues for potential therapeutic interventions in the management of COVID-19.

Evaluating Nirmatrelvir-Ritonavir (Paxlovid®) in Outpatient COVID-19 Treatment: Safety, Tolerability, and Adherence Insights from Primary Healthcare Clinics (preprint)

Objective: This study aims to fill this gap by evaluating the safety, tolerability, and adherence of patients prescribed Paxlovid® in outpatient settings, focusing on its use in managing category 2 COVID-19 patients across three primary healthcare clinics in Selangor, Malaysia. Design: Retrospective cross-sectional study Setting: Data were collected from the Paxlovid® pharmacy registry and medical records at Klinik Kesihatan Seksyen 7, Klinik Kesihatan Seksyen 19, and Klinik Kesihatan Kelana Jaya between April 1, 2022, and November 30, 2022. Participants: This study analysed data from 415 category 2 COVID-19 patients aged ≥18 years old. Primary and secondary outcomes: Parameters assessed included patient demographics, dosing, current medication, changes in drug regimen, adherence, and ADR. Pharmacists follow-ups were conducted on days 3 and 5 post-medication initiation. Results: The majority (79.5%) of the cohort experienced ADR, predominantly dysgeusia, diarrhoea, body ache, vomiting, and nausea. Despite these, the ADR were generally well-tolerated, with no severe impacts reported. High adherence was observed, with 96.9% of patients completing the 5-day regimen. The primary reasons for non-adherence included adverse effect intolerability, dosing ambiguity, forgetfulness, concerns about ADR, and perceived health improvement. Notable medications interacting with Paxlovid® were simvastatin, amlodipine, and atorvastatin, and 21.7% of 23 concurrent medications were found not complying to the recommended interventions by the University of Liverpool COVID-19 Drug Interaction database. Conclusion: Nirmatrelvir-ritonavir (Paxlovid®) demonstrates a high level of safety and tolerability in outpatient COVID-19 patients, with optimal adherence observed. This study underscores the vital role of healthcare professionals in managing Paxlovid® within primary healthcare and highlights the need for broader research and direct patient involvement to enhance treatment strategies against COVID-19.

WHAT THE COVID-19 PANDEMIC TAUGHT US IN CHILDREN (preprint)

Objective: The COVID-19 pandemic is an important cause of morbidity and mortality, which has had a negative impact worldwide. We aimed to contribute to the medical literature by sharing the knowledge and experience of pediatric patients who were diagnosed as having COVID-19 in a one-year period. Method: Patients aged 1 month to 18 years who were diagnosed as having COVID-19 in our clinic, between March 2020 and April 2020, from when COVID-19 was declared as a pandemic, were included in the study. Results: Four hundred sixty-seven children were included in the study. There were 34 (7.3%) patients under one year of age, 111 (23.8%) between 1-5 years, 98 (30.4%) between 5-10 years, 142 (30.4%) between 11-15 years, and 82 (17.6%) age over 15 years. Fever (88.2%), vomiting (32.4%), and diarrhea (29.4%) in patients aged under 1 year, sore throat (36.6%) in patients aged 11-15 years, and dysgeusia (11%), anosmia (14.6%), headache (18.3%), malaise (40.8%), myalgia (28%), and dyspnea (17.1%) in those aged over 15 years of age were found significantly more common compared with the other age groups. Thirty-five (7.5%) patients were asymptomatic, 365 (78.1%) had mild disease, 35 (7.5%) were moderate, 27 (5.8%) were severe, and five (1.07%) were critical. Leukocyte count, erythrocyte sedimentation rate, ferritin, and C-reactive protein values were significantly higher in hospitalized patients. Four patients died during the study period (0.8%, 4/494). Conclusion: Although COVID-19 has an asymptomatic and mild course in children, it should be kept in mind that it may have a severe course.

Dysosmia and dysgeusia as differential diagnostics for clinical triaging of COVID-19 cases (preprint)

Smell and taste disorders are recognized as frequent, and often the only, signs occurring in the early phase of SARS-Cov-2 infection and in many cases perdure as post-viral symptoms. This evidence raised a general reconsideration of chemosensory deficits, further suggesting that their appearance can be considered as a discriminative and predictive tool to detect COVID-19 cases. In this study, encompassing the first and second pandemic wave, participants estimated their olfactory and gustatory sensitivity, plus they were administered the validated Brief Smell Identification Test (BSIT). We observed that smell and taste impairments were mainly experienced by COVID-19-positive subjects with comparable severity of respiratory symptoms as non-COVID-19 patients. In addition, we noticed that the diagnostic power of subjective olfactory assessments upon SARS-Cov-2 infection is comparable to quantitative evaluation, suggesting that self-reporting could be adopted as the first line of intervention, anticipating more exhaustive procedures aimed at containing COVID-19 diffusion and consequently preserving general health. Overall, results from this work share similarity with other studies, therefore further underlying that olfactory and gustatory disbalance can be distinctive hallmarks in COVID-19 continuum.

The impact of injury of the chorda tympani nerve during primary stapes surgery or cochlear implantation on taste function, quality of life and food preferences: A study protocol for a double-blind prospective prognostic association study.

BACKGROUND: The chorda tympani nerve (CTN) is a mixed nerve, which carries sensory and parasympathetic fibres. The sensory component supplies the taste sensation of the anterior two-thirds of the ipsilateral side of the tongue. During middle ear surgery the CTN is exposed and frequently stretched or sacrificed, because it lacks a bony covering as it passes through the middle ear. Injury may cause hypogeusia, ageusia or altered taste sensation of the ipsilateral side of the tongue. To date, there is no consensus regarding which type of CTN injury (sacrificing or stretching), during middle ear surgery, leads to the least burden for the patient. METHODS: A double-blind prospective prognostic association study was designed in a single medical centre in the Netherlands to determine the effect of CTN injury on postoperative taste disturbance and quality of life. 154 patients, who will undergo primary stapes surgery or cochlear implantation will be included. The taste sensation, food preferences and quality of life of these patients will be evaluated preoperatively and at one week, six weeks and six months postoperatively using the Taste Strip Test, Electrogustometry, supplementary questionnaire on taste disturbance, Macronutrient and Taste Preference Ranking Task, Appetite, Hunger and Sensory Perception questionnaire and Questionnaire of Olfactory Disorders to assess the association of these outcomes with CTN injury. Evaluation of olfactory function will only take place preoperatively and at one week postoperatively using the Sniffin' Sticks. The patient and outcome assessor are blinded to the presence or absence of CTN injury. DISCUSSION: This study is the first to validate and quantify the effect of chorda tympani nerve injury on taste function. The findings of this study may lead to evidence-based proof of the effect of chorda tympani injury on taste function with consequences for surgical strategies. TRIAL REGISTRATION: Netherlands Trial Register NL9791. Registered on 10 October 2021.

Prevalence of symptoms, comorbidities, and reinfections in individuals infected with Wild-Type SARS-CoV-2, Delta, or Omicron variants: a comparative study in western Mexico.

Introduction: The variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been classified into variants of interest (VOIs) or concern (VOCs) to prioritize global monitoring and research on variants with potential risks to public health. The SARS-CoV-2 high-rate mutation can directly impact the clinical disease progression, epidemiological behavior, immune evasion, vaccine efficacy, and transmission rates. Therefore, epidemiological surveillance is crucial for controlling the COVID-19 pandemic. In the present study, we aimed to describe the prevalence of wild-type (WT) SARS-CoV-2 and Delta and Omicron variants in Jalisco State, Mexico, from 2021 to 2022, and evaluate the possible association of these variants with clinical manifestations of COVID-19. Methods: Four thousand and ninety-eight patients diagnosed with COVID-19 by real-time PCR (COVIFLU, Genes2Life, Mexico) from nasopharyngeal samples from January 2021 to January 2022 were included. Variant identification was performed by the RT-qPCR Master Mut Kit (Genes2Life, Mexico). A study population follow-up was performed to identify patients who had experienced reinfection after being vaccinated. Results and Discussion: Samples were grouped into variants according to the identified mutations: 46.3% were Omicron, 27.9% were Delta, and 25.8% were WT. The proportions of dry cough, fatigue, headache, muscle pain, conjunctivitis, fast breathing, diarrhea, anosmia, and dysgeusia were significantly different among the abovementioned groups (p < 0.001). Anosmia and dysgeusia were mainly found in WT-infected patients, while rhinorrhea and sore throat were more prevalent in patients infected with the Omicron variant. For the reinfection follow-up, 836 patients answered, from which 85 cases of reinfection were identified (9.6%); Omicron was the VOC that caused all reported reinfection cases. In this study, we demonstrate that the Omicron variant caused the biggest outbreak in Jalisco during the pandemic from late December 2021 to mid-February 2022 but with a less severe form than the one demonstrated by Delta and WT. The co-analysis of mutations and clinical outcomes is a public health strategy with the potential to infer mutations or variants that could increase disease severity and even be an indicator of long-term sequelae of COVID-19.

Oral cavity manifestations in COVID-19 patients: A cross-sectional study (preprint)

Objective To determine the prevalence of oral manifestations in symptomatic patients in the ambulatory setting with suspected COVID-19. Methods This cross-sectional study evaluated oral manifestations in adults (aged ≥ 18 years) with suspected and confirmed SARS-CoV-2 infection. Chi-square and Fisher’s exact tests were used to compare data between the groups (RT-PCR-positive and RT-PCR-negative patients). Results One hundred and thirty-sixparticipants were included. Mostwere female (n = 79; 58.1%), mean age of 39.53 (± 14.17) years. Of these, 54 (39.7%) had a positive RT-PCR test, and 82 (60.3%) had negative RT-PCR results. Oral manifestations were observed in 40 participants (74.1%)in the RT-PCR-positive group and in 67 participants (81.7%) in the RT-PCR-negative group. The most common oral manifestations were xerostomia (n = 85; 62.5%) and dysgeusia/ageusia (n = 57; 41.9%). Different rates of gingivitis (n = 12; 22.2% vs n = 5; 6.1%) and halitosis (n = 7; 13.0% vs n = 1; 1.2%) were observed between the RT-PCR-positive and negative groups, respectively. Mouth ulcers, glossitis, tongue coating, and petechiae were reported in both groups, without significant differences. Conclusions A high prevalence of oral manifestations was observed in symptomatic patients with suspected or confirmed COVID-19. Clinical Relevance This study highlights the importance of routine oral examinations by dentists as part of the multidisciplinary care of COVID-19 patients.

Association between salivary SARS-CoV-2 viral load and acute and late symptoms of COVID-19 in non- hospitalized patients: A cohort study (preprint)

Background The clinical course of COVID-19 can be divided into two phases: acute and late.Aims This study evaluated the association between salivary SARS-CoV-2 load and acute and late symptoms of COVID-19 in non-hospitalized patients.Methods This cohort study included 109 participants who tested positive for SARS-CoV-2 in a rapid antigen test (Ethics Committee, 4.434.828). Saliva samples were obtained and acute symptoms were recorded immediately after the diagnosis of COVID-19. Late symptoms were recorded 3 months later. The viral load was estimated based on real-time reverse transcription polymerase chain reaction (qRT-PCR) cycle threshold (Ct). The chi-square and Student t test were used to assess the association between salivary viral load and symptoms (p ≤ 0.05).Results A lower salivary viral load was associated with diarrhea (RR = 0.73, 95% CI = 0.55–0.97, p = 0.04), anosmia (RR = 0.63, 95% CI = 0.47–0.84, p = 0.002), and dysgeusia (RR = 0.69, 95% CI = 0.52–0.91, p = 0.01) in the acute phase of the infection. Regarding late symptoms, a lower viral load remained associated with anosmia (RR = 0.68, 95% CI = 0.51–0.90, p = 0.05) and dysgeusia (RR = 0.59, 95% CI = 0.50–0.70, p = 0.03).Conclusion Lower viral load is a known marker of mild COVID-19. The association of lower viral load with anosmia and dysgeusia in the acute and late phases of the disease and with diarrhea in the acute phase suggests that these symptoms are predictive of mild COVID-19.

Predictors of Mortality in Hospitalized Patients with COVID-19: A One-Year Case-Control Study (preprint)

Objective: To determine the associated factors with mortality, in addition to age and sex, in a high-complexity hospital in Bogota, Colombia, during the first year of the pandemic. Design: A case-control study. Setting: High-complexity center above 2,640 meters above sea level (masl) in Colombia. Methods: A case-control study was conducted on 564 patients admitted to the hospital with confirmed COVID-19. Deceased patients (n: 282) and a control group (n: 282), matched by age, sex, and month of admission, were included. Clinical and paraclinical variables were retrospectively obtained by systematic revision of clinical records. Multiple imputations by chained equation (MICE) were implemented to account for missing variables. Classification and regression trees (CART) were estimated to evaluate the interaction of associated factors on admission and their role in predicting mortality during hospitalization. Results: Most of the patients included were males in the seventh decade of life. Most of the admissions occurred between July and August 2021. Surprisingly, recovered patients reported heterogeneous symptomatology, whereas deceased patients were most likely to present respiratory distress, dyspnea, and seizures on admission. In addition, the latter group exhibited a higher burden of comorbidities and alterations in laboratory parameters. After the imputation of datasets, CART analysis estimated 14 clinical profiles based on respiratory distress, LDH, dyspnea, hemoglobin, D-dimer, ferritin, blood urea nitrogen, C-reactive protein, PaO2/FiO2, dysgeusia, total bilirubin, platelets, and gastroesophageal reflux disease. The accuracy model for prediction was 85.6% (P < 0.0001). Conclusion: Multivariate analysis yielded a reliable model to predict mortality in COVID-19. This analysis revealed new interactions between clinical and paraclinical features in addition to age and sex. Furthermore, this predictive model could offer new clues for the personalized management of this condition in clinical settings. Keywords: SARS-CoV-2, COVID-19, Mortality, Predictors, Risk Factors

[Mechanisms and Management of COVID-19-Associated Taste Disorders].

The taste buds in the human tongue contain specialized cells that generate taste signals when they are stimulated. These signals are then transmitted to the central nervous system, allowing the human body to distinguish nutritious substances from toxic or harmful ones. This process is critical to the survival of humans and other mammals. A number of studies have shown that dysgeusia, or taste disorder, is a common complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which can severely affect patients' nutritional intake and quality of life. Based on the physiological process of taste perception, the direct causes of dysgeusia include dysfunction of taste receptors and damage to the taste nervous system, while indirect causes include genetic factors, aging-related changes, bacterial and viral infections, and cancer treatments such as radiotherapy and chemotherapy. The pathogenic factors of dysgeusia are complicated, further research is needed to fully understand the underlying mechanisms, and some of the reported findings and conclusions still need further validation. All these form a great challenge for clinical diagnosis of the cause and targeted treatment of dysgeusia. Herein, we reviewed published research on the physiological process of taste perception, the potential mechanisms of taste disorders related to SARS-CoV-2 infection, and strategies for prevention and treatment, providing theoretical support for establishing and improving the comprehensive management of COVID-19 complicated by taste disorders.

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.

Attributes of dysgeusia and anosmia of coronavirus disease 2019 (COVID-19) in hospitalized patients.

OBJECTIVES: While chemosensory dysfunctions, dysgeusia and anosmia/hyposmia, are recognized as distinctive symptoms of COVID-19, their temporality of presentation and association with the patient age, gender, disease severity, and comorbidities has been sparsely studied. Hence, we evaluated the latter associations of chemosensory dysfunction, in hospitalized COVID-19 patients in the United Arab Emirates (UAE). MATERIALS AND METHODS: Information on chemosensory dysfunction and history of chronic systemic comorbidities, if any, was obtained from 149 COVID-19 patients in an infectious disease hospital in UAE, using their medical records, as well as from a face-to-face questionnaire survey. Additionally, a modified SNOT-22 questionnaire that measures disease-specific quality of life in patients with upper respiratory tract affections was also administered. RESULTS: Chemosensory dysfunction was reported by 94.6% of the cohort, and anosmia with dysgeusia was significantly more in males than females with severe COVID-19. Males with moderate COVID-19 and systemic comorbidities were more likely to present with chemosensory dysfunction in comparison with females. SNOT-22 questionnaire revealed that nasal blockage and runny nose were more prevalent in mild/moderate, than in the severe, state of COVID-19. CONCLUSION: Our data confirm the commonality of chemosensory dysfunction during COVID-19 progression, and the significantly more pronounced combined dysfunction in males with severe COVID-19, and comorbidities.

Association between SARS-CoV-2 variants and post COVID-19 condition: findings from a longitudinal cohort study in the Belgian adult population (preprint)

Background: While many studies on the determinants of post-COVID-19 conditions (PCC) have been conducted, little is known about the relationship between SARS-CoV-2 variants and PCC. This study aimed to assess the association between different SARS-CoV-2 variants and the probability of having PCC three months after the infection. Methods: This study was a longitudinal cohort study conducted between April 2021 and September 2022 in Belgium. In total, 8,238 adults with a confirmed SARS-CoV-2 infection were followed up between the time of their infection and three months later. The primary outcomes were the PCC status three months post infection and seven PCC symptoms categories (neurocognitive, autonomic, gastrointestinal, respiratory, musculoskeletal, anosmia and/or dysgeusia, and other manifestations). The main exposure variable was the type of SARS-CoV-2 variants (i.e. Alpha, Delta, and Omicron), extracted from national surveillance data. The association between the different SARS-CoV-2 variants and PCC as well as PCC symptoms categories was assessed using multivariable logistic regression. Results: The proportion of PCC among participants infected during the Alpha, Delta, and Omicron-dominant periods was significantly different and respectively 50%, 50%, and 37%. Participants infected during the Alpha- and Delta-dominant periods had a significantly higher odds of having PCC than those infected during the Omicron-dominant period (OR = 1.61, 95% confidence interval [CI] = 1.33–1.96 and OR = 1.73, 95%CI = 1.54–1.93, respectively). Participants infected during the Alpha and Delta-dominant periods were more likely to report neurocognitive, respiratory, and anosmia/dysgeusia symptoms of PCC. Conclusions: People infected during the Alpha- and Delta-dominant periods had a higher probability of having PCC three months after infection than those infected during the Omicron-dominant period. The lower probability of PCC with the Omicron variant must also be interpreted in absolute figures. Indeed, the number of infections with the Omicron variant being higher than with the Alpha and Delta variants, it is possible that the overall prevalence of PCC in the population increases, even if the probability of having a PCC decreases.

Clinical Characteristics and Long-term Symptomology of Post-COVID-19 Olfactory and Gustatory Dysfunction (preprint)

Olfactory and gustatory dysfunction persists in up to 4% of patients who have recovered from COVID19 beyond 6 months. Dysosmia (distorted smell) and dysgeusia (distorted taste) are frequently observed in the acute phase of many upper respiratory viral infections. However, persistent dysosmia in these patients is associated with persistent nasal inflammation. The purpose of this study was to determine the extent of patient self-assessed post-COVID-19 olfactory and gustatory dysfunction and to understand the quality and severity of the subjective symptoms over a year. A total of 426 registry participants were recruited to complete initial online questionnaires and follow up at three post-enrollment time points: 3 months, 6 months, 12 months. The Registry questionnaires assessed nasal inflammation (Sino Nasal Outcome Test - SNOT22), mental health (The Patient Health Questionnaire 2 PHQ2; Neuro QoL Positive Affect and Well-Being PAW 23), sleep quality (The Pittsburgh Sleep Quality Index PSQI), In a cohort of 74 patients, clinical measurements of smell (Smell Identification Test (UPSIT) and taste (Waterless Taste Test (B-WETT)) were performed to validate self-reported measures of sensory impairment. Our data indicate that persistent COVID19 olfactory and gustatory dysfunction is not associated with subjective measures of nasal inflammation. However, dryness of the nose/mouth, mood disturbance, and poor sleep quality are reported by the majority of participants. Participants struggle with detecting specific foul/dangerous odorants and tasting subtle flavors, which could have a negative effect on patient safety and well-being. Those infected during the earlier waves of the pandemic have more persistent and severe symptoms. Objective measure of both smell and taste are significantly reduced in the majority of participants with self-reported olfactory and gustatory dysfunction. Finally, standard anti-inflammatory topical and systemic therapy does not improve the subjective sense of smell while olfactory training is marginally more effective. This establishes persistent COVID19 olfactory and gustatory dysfunction as a chronic and difficult to treat syndrome resistant to standard anti-inflammatory therapy.

A cross-sectional, multicenter survey of the prevalence and risk factors for Long COVID.

Long-term sequelae of the coronavirus disease (COVID-19) constitute Long COVID. Although Long COVID has been reported globally, its risk factors and effects on quality of life (QOL) remain unclear. We conducted a cross-sectional study using questionnaires and electronic medical records of COVID-19 patients who were diagnosed or hospitalized at five facilities in Japan. Responses were obtained from 285 out of 1,150 patients. More than half of the participants reported Long COVID symptoms of varying severity 1 year after COVID-19. Common sequelae included fatigue, dyspnea, alopecia, concentration problems, memory problems, sleeplessness, and joint pain, which often significantly reduced their QOL. COVID-19 severity was strongly associated with sputum production, chest pain, dyspnea, sore throat, and diarrhea, but not with fatigue, dysgeusia, anosmia, alopecia, and sleeplessness. Fatigue, dysgeusia, anosmia, alopecia, and sleeplessness affected the QOL among participants with asymptomatic or mild COVID-19 during the acute phase. Moreover, these sequelae persisted for prolonged periods.

Drug-induced olfactory and gustatory dysfunction: Analysis of FDA adverse events reporting system.

OBJECTIVES: With the COVID-19 pandemic, there is growing interest and research in olfactory and gustatory dysfunction (OGD). Drug-induced dysfunction is an often overlooked etiology. While several medications include smell or taste disturbance as a side effect, there are no publications describing which medications are most frequently implicated. We aim to describe the patterns of these adverse drug reactions (ADRs) using the FDA Adverse Events Reporting System (FAERS). METHODS: The FAERS database was queried from 2011 to 2021 for terms describing ADRs related to OGD. Terms included anosmia, hyposmia, olfactory test abnormal, olfactory nerve disorder, hallucination olfactory, parosmia, ageusia, hypogeusia, dysgeusia, and taste disorder. We identified the top reported medications associated with general smell dysfunction, general taste dysfunction, reduced smell, and altered smell. RESULTS: From 2011 to 2021, 16,091 ADRs were reported with OGD, of which13,641 (84.8%) and 2,450 (15.2%) were associated with gustatory and olfactory reactions, respectively. Zinc products (370 reports) and fluticasone propionate (214) were most commonly associated with olfactory dysfunction, specifically reduced olfaction. Varenicline (24) and fluticasone propionate (23) were most commonly associated with altered smell. Lenalidomide (490) and sunitinib (468) were most commonly associated with gustatory dysfunction. Antineoplastic and immunomodulating medications accounted for 21.6% and 36.3% of olfactory and gustatory ADRs, respectively. Among this category, immunoglobulin drugs were the most commonly associated with OGD ADRs. CONCLUSION: Gustatory dysfunction is more commonly reported ADR compared with olfactory dysfunction. Immunologic/rheumatologic medications are the leading culprit of reported OGD. With increasing numbers of patients presenting to otolaryngologists for OGD, it is important to consider drug-induced etiology. LEVEL OF EVIDENCE: III.

Association between Clinical Frailty Scale (CFS) and clinical presentation and outcomes in older inpatients with COVID-19.

BACKGROUND: Frailty is a physiological condition characterized by a decreased reserve to stressors. In patients with COVID-19, frailty is a risk factor for in-hospital mortality. The aim of this study was to assess the relationship between clinical presentation, analytical and radiological parameters at admission, and clinical outcomes according to frailty, as defined by the Clinical Frailty Scale (CFS), in old people hospitalized with COVID-19. MATERIALS AND METHODS: This retrospective cohort study included people aged 65 years and older and admitted with community-acquired COVID-19 from 3 March 2020 to 31 April 2021. Patients were categorized using the CFS. Primary outcomes were symptoms of COVID-19 prior to admission, mortality, readmission, admission in intensive care unit (ICU), and need for invasive mechanical ventilation. Analysis of clinical symptoms, clinical outcomes, and CFS was performed using multivariable logistic regression, and results were expressed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 785 included patients, 326 (41.5%, 95% CI 38.1%-45.0%) were defined as frail (CFS ≥ 5 points): 208 (26.5%, 95% CI 23.5%-29.7%) presented mild-moderate frailty (CFS 5-6 points) and 118 (15.0%, 95% CI 12.7%-17.7%), severe frailty (7-9 points). After adjusting for epidemiological variables (age, gender, residence in a nursing home, and Charlson comorbidity index), frail patients were significantly less likely to present dry cough (OR 0.58, 95% CI 0.40-0.83), myalgia-arthralgia (OR 0.46, 95% CI 0.29-0.75), and anosmia-dysgeusia (OR 0.46, 95% CI 0.23-0.94). Confusion was more common in severely frail patients (OR 3.14; 95% CI 1.64-5.97). After adjusting for epidemiological variables, the risk of in-hospital mortality was higher in frail patients (OR 2.79, 95% CI 1.79-4.25), including both those with mild-moderate frailty (OR 1.98, 95% CI 1.23-3.19) and severe frailty (OR 5.44, 95% CI 3.14-9.42). Readmission was higher in frail patients (OR 2.11, 95% CI 1.07-4.16), but only in mild-moderate frailty (OR 2.35, 95% CI 1.17-4.75).. CONCLUSION: Frail patients presented atypical symptoms (less dry cough, myalgia-arthralgia, and anosmia-dysgeusia, and more confusion). Frailty was an independent predictor for death, regardless of severity, and mild-moderate frailty was associated with readmission.

Post coronavirus disease 2019 condition in children at a children's hospital in Japan.

BACKGROUND: Acute coronavirus disease 2019 (COVID-19) is associated with chronic symptoms. These have been termed the "post COVID-19 condition." The data on this condition in children are still limited. We therefore aimed to elucidate the characteristics of this post COVID-19 condition. METHODS: Children referred to a long COVID-19 clinic were included at Tokyo Metropolitan Children's Medical Center between October 2021 and July 2022. Children with another diagnosis and those who failed to meet criteria for post COVID-19 condition were excluded. Demographic and clinical data were collected retrospectively. RESULTS: Of 33 referrals, nine were excluded, and 24 fulfilled the criteria for post COVID-19 condition. The median age and percentage of girls were 12.5 (IQR: 11-13) years and 29.2%, respectively. All the patients had mild, acute COVID-19. Dysgeusia and brain fog was observed more frequently during the Delta and Omicron variant periods, respectively. School absenteeism >4 weeks was observed in 41.6% of the patients. Common symptoms included malaise, headache, dysgeusia, and dysosmia. The median duration of post COVID-19 condition was 4.5 (IQR: 2.8-5.2) months. Pain management and counseling using the pacing approach were the most commonly offered treatments. Symptom resolution and improvement was observed in 29.2% and 54.2% of the patients, respectively. CONCLUSIONS: One third of the patients referred for long COVID did not fit the definition of the post COVID-19 condition. After a median follow up of 4.5 months, the majority of the cases resolved or improved.

Transient Anosmia and dysgeusia in COVID-19 disease: a cross-sectional study (preprint)

Objective: This study aims to explore the prevalence of anosmia and dysgeusia and their impact on COVID-19 patients. Design: This is a cross-sectional study. Patients diagnosed with COVID-19 between 1st October 2020 and 30th June 2021 were randomly selected from a national COVID-19 registry. The Anosmia Reporting Tool and a brief version of the questionnaire on olfactory disorders were used to measure the outcomes via telephone interviews. Data were analyzed using SPSS 27 statistics software. Results: A total of 405 COVID-19 adults were included in this study, 220 (54.3%) were males and 185 (45.8%) were females. The mean±SD age of participants was 38.2 ± 11.3 years. Alterations in the sense of smell and taste were reported by 206 (50.9%), and 195 (48.1%) of the patients respectively. Sex and nationality of participants were significantly associated with anosmia and dysgeusia (p<0.001) and (p-value=0.001) respectively. Among patients who experienced anosmia and dysgeusia, alterations in eating habits (64.2%), impact on mental wellbeing (38.9%), concerns that the alterations were permanent (35.4%), and physical implications and difficulty performing activities of daily living (34% ) were reported. Conclusion: Anosmia and dysgeusia are prevalent symptoms of COVID-19 disease, especially among females. Neuropsychological implications of COVID-19 in the acute infection phase and prognosis of anosmia and dysgeusia in COVID-19 are areas for further exploration.

Oral manifestations of COVID-19 correlated to medical and drug history, a survey on infected medical doctors. (preprint)

Objective Reporting the oral symptoms of COVID-19 and correlate the occurrence of these symptoms with various possible etiologic factors. Methods A cross-sectional web-based survey targeted Medical doctors infected with COVID-19. The survey questioned the diagnosis of the disease, the severity of the disease symptoms, the oral symptoms along with drug and medical history. A total sample of 312 response were analyzed and correlated with various factors including the patients’ age, sex, medical history, drug history, hospitalization and severity of COVID-19 symptoms. Results Oral manifestations were reported in 72.5% of the participants. The most common oral manifestations were dysgeusia in 76% of patients which was partial in 64% of the participants. Xerostomia was reported in 41.6% of cases. Aphthous stomatitis and recurrent herpetic infections were also reported. The occurrence of oral symptoms was increased among population with previous medical history with no evidence of correlation with any other factors regarding gender, certain medications or oral hygiene. Conclusion The most common oral manifestations of COVID-19 are dysgeusia and xerostomia and the occurrence of oral manifestations is increased in patients with previous medical condition. Clinical relevance: awareness of the possible symptoms and medical conditions that may potentiate the severity of oral symptoms during COVID-19 infection allows targeting the precise mechanism to treat the oral symptoms.