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Long COVID presents with diverse symptoms after COVID-19. Different clusters of symptoms have been reported; however, their persistence beyond 2 years after COVID-19 remains unclear. In this cohort study, we prospectively evaluated individuals with previous severe COVID-19 presenting with long COVID at a two-year follow-up. We characterized the included patients and performed a cluster analysis of symptoms through multiple correspondence analysis and hierarchical clustering. A total of 199 patients with long COVID were included. The median age was 58 years (48-69), 56% were male, and the median follow-up time since the COVID-19 diagnosis was 26 months (IQR: 25, 27). Three symptom clusters were identified: Cluster 1 is characterized by fatigue, myalgia/arthralgia, a low prevalence of symptoms, and a lack of specific symptoms; Cluster 2 is defined by a high prevalence of fatigue, myalgia/arthralgia, and cardiorespiratory symptoms, including palpitations, shortness of breath, cough, and chest pain; and Cluster 3 is demonstrated a high prevalence of ageusia, anosmia, fatigue, and cardiorespiratory symptoms. Our study reinforces the concept of symptom clustering in long COVID, providing evidence that these clusters may persist beyond two years after a COVID-19 diagnosis. This highlights the chronic and debilitating nature of long COVID and the importance of developing strategies to mitigate symptoms in these patients.

Aim: To systematically review the cases of anosmia or ageusia after receiving the coronavirus disease 2019 (COVID-19) vaccine. Methods: A systematic search was conducted in electronic databases, including Web of Science, Scopus, Embase, and PubMed, to identify any published study that evaluated the anosmia or ageusia after receiving the COVID-19 vaccine, including case reports, case series, letter to editor articles with reported cases regarding our topic, or observational studies with at least 1 eligible patient consisted with our criteria. We excluded the studies that reported anosmia or ageusia due to COVID-19 infection and non-COVID-19 vaccines. Results: Five studies consisting of 11 patients were included in this systematic review. Of the 11 patients, 5 patients had received the Pfizer COVID-19 vaccine and 6 patients received the Oxford-AstraZeneca COVID-19 vaccine, of which 6 patients developed symptoms after the first dose of vaccination and 5 patients were symptomatic after the second vaccine dose. Most of the patients developed symptoms within 1 week after the vaccination. The disorders of the patients included partial or total anosmia, parosmia, phantosmia, hyposmia, ageusia, and dysgeusia. Also, the patients had symptoms other than smell or taste disorders, including arthralgia, fever, chills, rhinorrhea, myalgia, abdominal pain, fatigue, muscle weakness, altered bowel pattern, aural fullness, tinnitus, and headache. Most of the evaluated patients did not receive any treatment as for their disorders. However, in some cases, treatment with oral corticosteroids or dietary supplementation was required. Conclusion: Anosmia and ageusia are important symptoms of COVID-19 vaccination. These symptoms will resolve without any treatment in most cases, although some interventions may be needed in some patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A 70-year-old right-handed housewife suffered an acute loss of taste, an unpleasant change in the taste of foods and liquids, and a strong aversion to all kinds of food due to a small lacune in the right dorsomedial pontine tegmentum. Eating became so unpleasant that she lost 7 kg in three weeks. Olfaction and the sensibility of the tongue were spared. The right medial longitudinal fascicle, the central tegmental tract, or both, were injured by the tegmental lesion. A discrete right-sided lesion in the upper pontine tegmentum may cause a reversible syndrome consisting of bilateral hypogeusia which is more severe ipsilaterally.

Recent literature indicates that post-COVID-19 patients suffer from a plethora of complications, including chemosensory dysfunction. However, little attention has been given to understand the interactions between chemosensory, trigeminal, and salivary dysfunctions in these patients. The aims of this study were (1) to investigate the prevalence and combinations of chemosensory, trigeminal, and salivary dysfunctions, (2) to identify the odorants/tastants that are compromised, and (3) to explore possible associations between the four dysfunctions in post-COVID-19 patients. One hundred post-COVID-19 patients and 76 healthy controls (pre-COVID-19) were included in this cross-sectional, case-controlled study. Participants' smell, taste, trigeminal, and salivary functions were assessed. The patients had a significantly higher prevalence of parosmia (80.0%), hyposmia (42.0%), anosmia (53.0%), dysgeusia (34.0%), complete ageusia (3.0%), specific ageusia (27.0%), dysesthesia (11.0%) and dry mouth (18.0%) compared to controls (0.0% for all parameters, except 27.6% for hyposmia). Complete loss of bitter taste was the most prevalent specific ageusia (66.7%) and coffee was the most common distorted smell (56.4%). Seven different combinations of dysfunction were observed in the patients, the most common being a combination of olfactory and gustatory dysfunction (48.0%). These findings indicate that post-COVID-19 patients experience a range of chemosensory, trigeminal, and salivary disturbances, occurring in various combinations., (© 2024. The Author(s).)

Background: Previous meta-analyses estimating the prevalence of the post-COVID-19 condition (PCC) were confounded by the lack of negative control groups. This may result in an overestimation of the prevalence of those experiencing PCC, as these symptoms are non-specific and common in the general population. In this study, we aimed to compare the burden of persistent symptoms among COVID-19 survivors relative to COVID-19-negative controls., Methods: A systematic literature search was conducted using the following databases (PubMed, Web of Science, and Scopus) until July 2023 for comparative studies that examined the prevalence of persistent symptoms in COVID-19 survivors. Given that many of the symptoms among COVID-19 survivors overlap with post-hospitalization syndrome and post-intensive care syndrome, we included studies that compare the prevalence of persistent symptoms in hospitalized COVID-19 patients relative to non-COVID-19 hospitalized patients and in non-hospitalized COVID-19 patients relative to healthy controls that reported outcomes after at least 3 months since infection. The results of the meta-analysis were reported as odds ratios with a 95% confidence interval based on the random effects model., Results: Twenty articles were included in this study. Our analysis of symptomatology in non-hospitalized COVID-19 patients compared to negative controls revealed that the majority of symptoms examined were not related to COVID-19 infection and appeared equally prevalent in both cohorts. However, non-COVID-19 hospitalized patients had higher odds of occurrence of certain symptoms like anosmia, ageusia, fatigue, dyspnea, and brain fog (P < 0.05). Particularly, anosmia and ageusia showed substantially elevated odds relative to the negative control group at 11.27 and 9.76, respectively, P < 0.05. In contrast, analysis of hospitalized COVID-19 patients compared to those hospitalized for other indications did not demonstrate significantly higher odds for the tested symptoms., Conclusions: The persistent symptoms in COVID-19 survivors may result from hospitalization for causes unrelated to COVID-19 and are commonly reported among the general population. Although certain symptoms exhibited higher odds in non-hospitalized COVID-19 patients relative to controls, these symptoms are common post-viral illnesses. Therefore, the persistent symptoms after COVID-19 may not be unique to SARS-CoV-2. Future studies including well-matched control groups when investigating persistent symptoms in COVID-19 survivors are warranted to draw a firm conclusion., (© 2024. The Author(s).)

Taste consists of sensation and perception. Specific neural structures transmit a stimulus from the taste buds to the gustatory cortex to generate taste sensation. Any disruption of this pathway, whether it affects sensation or perception, can result in taste disorders. Stereotactic procedures involving the thalamus may result in gustatory complications. A 41-year-old female patient who underwent stereotactic drainage of a thalamic cyst suffered transient ageusia. Subsequently, she developed metallic taste perception. When her stereotactic plan was re-evaluated, it was noted that the posteromedial ventral thalamus nucleus was in the path of the needle tract and the needle had passed through it. Follow-up was recommended and her symptoms completely resolved within 2 months following surgery. Modern imaging techniques allow for the visualization of neural structures related to the sense of taste. Additionally, care must be taken when planning stereotactic procedures for such lesions.

Objective: Aim: To review the publications subject to the problem of COVID-19 associated anosmia incidence in pediatric patients as well as its pathogenesis, diagnostics, treatment and recovery. The peculiarity of pediatric COVID-19 anosmia is due to children accounting for very low percentage of COVID-19 patients (comparing to one in adults), mostly with milder course of the disease. Awareness of anosmia and its proper diagnostics is crucial in children and adolescents, considering it can be the only manifestation in COVID-19 positive pediatric patients., Patients and Methods: Materials and Methods: In order to achieve this goal a meta-analysis of information from databases followed by statistical processing and generalisation of the obtained data was carried out., Conclusion: Conclusions: Publications on COVID-19 anosmia in children and adolescents are less numerous than those concerning adult patients, so it is important to use every single trustworthy one. Anosmia/ageusia may be the only symptom, early identifier and the strongest predictor of COVID-19 infection in pediatric patients. Prospects for further scientific researches. Further researches regarding differential diagnostics of COVID-19 and other infections, including seasonal influenza, manifesting with both olfactory and taste dysfunction as well as anosmia diagnostics in children and adolescents with autistic spectrum and different types of mental disorders are possible.

Purpose: While the gustatory pathway of animals has been well-researched, that of humans is still a mystery. Several theories have been established, and some earlier reports hypothesized the relation to laterality. However, some cases could not be fully explained by the laterality theory (1). To clarify the gustatory pathway, we reported a case with bilateral hypogeusia after right thalamic infarction., Case: This 55-year-old, right-handed man suffered from sudden decreased sensitivity of taste. He was unable to differentiate sweetness and saltiness at bilateral anterior parts of tongue. Additionally, there was numbness at the upper palate and the lips. Neurological examination revealed decreased taste sense at both sides of his anterior tongue and decreased pin-prick sensation of the left part of his lips. Brain magnetic resonance imaging (MRI) revealed acute ischemic stroke at the right ventral posteromedial nucleus (VPM). Thus, single antiplatelet therapy was administered. Two weeks later, the symptoms improved significantly and completely recovered without sequelae., Conclusion: The exact gustatory pathway in humans remains uncertain nowadays. First, there were few reports about dysgeusia, which might be related to clinical neglect of taste deficits. Second, our knowledge of the human gustatory pathway depends solely on sporadic cases of taste-involved brain lesions. We reported a case of bilateral hypogeusia after right thalamic infarction. This finding indicates that, although there might be laterality of gustatory fibers to the left hemisphere, anatomical variations may exist in the human gustatory system. More research is needed to elucidate the understanding of the gustatory pathway in humans.

Objectives: The causes of hypogeusia include zinc deficiency, systemic illness, and consumption of drugs. Notably, patients with oral cavity diseases such as oral candidiasis and salivary gland hypofunction may present with risk factors that remain unreported. Hence, this study aimed to investigate the relationship between age, sex, smoking status, serum zinc concentration, oral candidiasis, saliva volume, and taste function in patients with hypogeusia., Subjects and Methods: Overall, 335 participants who complained of taste abnormalities underwent a taste test. Based on the recognition threshold value, the participants were classified as normal individuals (recognition threshold of 1 and 2) and patients with hypogeusia (recognition threshold of ≥3). The clinical characteristics, including resting saliva volume (RSV) and stimulated saliva volume (SSV), were compared, and a multivariate logistic regression analysis focusing on RSV was performed., Results: Patients with hypogeusia had a lower RSV than normal individuals for all tastes, but not for SSV. Based on the results of regression analysis, RSV was identified as an independent predictor of hypogeusia for salty and bitter tastes. Moreover, the proportion of patients with decreased RSV increased as the number of taste qualities exceeding the reference recognition threshold increased. Furthermore, a decrease in RSV was associated with an increase in the recognition threshold for salty and bitter tastes., Conclusions: Based on the results of the present study, moisturizing the oral cavity may be useful against hypogeusia., Competing Interests: Declaration of Competing Interest Authors have no relevant competing intereststo declare., (Copyright © 2023. Published by Elsevier Inc.)

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused a highly challenging and threatening situation worldwide. SARS-CoV-2 patients develop various clinical symptoms. The olfactory and taste dysfunctions are potential neurological manifestations among SARS-CoV-2 patients; however, their relationship with blood groups has rarely been investigated. This study aimed to investigate the prevalence of chemosensitive neurological disorders of smell and taste and their association with blood groups in SARS-CoV-2 patients. The present cross-sectional study was performed in the Department of Pathology, and Physiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. A well-structured, self-administered questionnaire was designed and distributed through social media platforms. A total of 922 Saudi and non-Saudi adults aged 18 years or older participated in the study. Out of 922 participants, the number of people who had anosmia was 309 (33.5%), 211 (22.9%) had hyposmia, and 45 (4.8%) had dysosmia. Moreover, 180 (19.52%) had ageusia, 47 (5.1%) and 293 (31.8%) had hypogeusia and dysgeusia, respectively. Among all the participants, 565 (61.27%) had smell-related disorders and 520 (56.39%) participants had taste-related clinical symptoms. The occurrence of anosmia and ageusia was relatively high among females compared to males ( p = 0.024). The prevalence of smell-related disorders was 25.0% (230) and taste-related disorders was 23.21% (214) among the study participants with blood group O compared to all other blood group (A, B, and AB) participants who have smell allied disorders 30.69% (283), and taste allied disorders 27.98% (258). The prevalence of chemosensitive neurological disorders involving impaired smell and taste was higher in SARS-CoV-2 patients. These clinical symptoms were common among the participants with blood group type O compared to all other ABO blood group types. The role of certain demographic characteristics was consistent throughout multiple studies, notably with female gender and young adults.

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., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Blijleven et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Deficits in motivational functioning including impairments in reward learning or reward sensitivity are common in psychiatric disorders characterized by anhedonia. Recently, anhedonic symptoms have been exacerbated by the pandemic caused by the Coronavirus disease 2019 (COVID-19) in the general population. The present study examined the putative associations between loss of smell (anosmia) and taste (ageusia) sensitivity, irrespective of COVID-19 infection, and anhedonia, measured by a signal-detection task probing the ability to modify behavior as a function of rewards (Probabilistic Reward Task; PRT). Tonic heart rate variability (HRV) was included in the model, due to its association with both smell and taste sensitivity as well as motivational functioning. The sample included 114 healthy individuals (81 females; mean age 22.2 years), who underwent a laboratory session in which dispositional traits, resting HRV and PRT performance were assessed, followed by a 4-days ecological momentary assessment to obtain daily measures of anosmia and ageusia. Lower levels of tonic HRV and lower momentary levels of smell and taste sensitivity were associated with impaired reward responsiveness and ability to shape future behavioral choices based on prior reinforcement experiences. Overall, the current results provide initial correlational evidence that could be fruitfully used to inform future experimental investigations aimed at elucidating the disruptive worldwide mental health consequences triggered by the pandemic., Competing Interests: Declaration of competing interest Over the past 3 years, Dr. Pizzagalli has received consulting fees from Albright Stonebridge Group, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics (formerly BlackThorn Therapeutics), Neurocrine Biosciences, Neuroscience Software, Otsuka, Sunovion, and Takeda; he has received honoraria from the Psychonomic Society and American Psychological Association (for editorial work) and from Alkermes; he has received research funding from the Brain and Behavior Research Foundation, the Dana Foundation, Millennium Pharmaceuticals, Wellcome Leap MCPsych, and NIMH; he has received stock options from Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software; he has a financial interest in Neumora Therapeutics, which has licensed the copyright to the Probabilistic Reward Task through Harvard University. No funding from these entities was used to support the current work, and all views expressed are solely those of the authors. All other authors have no conflicts of interest or relevant disclosures., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: We aimed to investigate the factors associated with neurological manifestations of post-coronavirus disease 2019 (COVID-19) conditions., Methods: We retrospectively collected data from 440 patients who visited our post-COVID-19 clinic more than 4 weeks after severe acute respiratory syndrome coronavirus 2 infection. We analyzed the prevalence of different neurological symptoms (brain fog, memory impairment, headache, and dizziness) and assessed the associated factors., Results: Brain fog was the most common symptom, observed in 170 patients (38.6%), followed by headaches (n = 137, 31.1%), dizziness (n = 128, 29%), and memory impairment (n = 104, 23.6%). Brain fog was associated with hyposmia or hypogeusia (odds ratio [OR], 2.54; P < 0.001), Fatigue Severity Scale (FSS) (OR, 1.06; P < 0.001), and Hospital Anxiety and Depression Scale-Anxiety (OR, 1.09; P = 0.037). Memory impairment was associated with sleep problems (OR, 2.83; P < 0.001), FSS (OR, 1.05; P < 0.001), and age (OR, 1.02; P = 0.015). Headache was associated with sleep problems (OR, 2.28; P = 0.001), sex (OR, 1.68; P = 0.042), and FSS (OR, 1.04; P < 0.001). Dizziness was associated with sleep problems (OR, 2.88; P < 0.001), and FSS (OR, 1.04; P < 0.001). The incidence of brain fog ( P < 0.001), memory impairment ( P < 0.001), dizziness ( P = 0.007), and headache ( P = 0.045) accompanied by hyposmia and hypogeusia was higher in patients with the aforementioned symptoms than in those without., Conclusion: This study suggests that there is a relationship between neurological symptoms and other clinical factors, such as fatigue, depression, anxiety, hyposmia, and hypogeusia., Competing Interests: The authors have no financial conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Chemosensory scientists have been skeptical that reports of COVID-19 taste loss are genuine, in part because before COVID-19 taste loss was rare and often confused with smell loss. Therefore, to establish the predicted prevalence rate of taste loss in COVID-19 patients, we conducted a systematic review and meta-analysis of 376 papers published in 2020-2021, with 235 meeting all inclusion criteria. Drawing on previous studies and guided by early meta-analyses, we explored how methodological differences (direct vs. self-report measures) may affect these estimates. We hypothesized that direct measures of taste are at least as sensitive as those obtained by self-report and that the preponderance of evidence confirms taste loss is a symptom of COVID-19. The meta-analysis showed that, among 138,015 COVID-19-positive patients, 36.62% reported taste dysfunction (95% confidence interval: 33.02%-40.39%), and the prevalence estimates were slightly but not significantly higher from studies using direct (n = 15) versus self-report (n = 220) methodologies (Q = 1.73, df = 1, P = 0.1889). Generally, males reported lower rates of taste loss than did females, and taste loss was highest among middle-aged adults. Thus, taste loss is likely a bona fide symptom of COVID-19, meriting further research into the most appropriate direct methods to measure it and its underlying mechanisms., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Scientific data regarding the prevalence of COVID-19 neurological manifestations and prognosis in Latin America countries is still lacking. Therefore, the study aims to understand neurological manifestations of SARS-CoV 2 infection and outcomes in the Brazilian population., Methods: This study is part of the Brazilian COVID-19 Registry, a multicentric cohort, including data from 37 hospitals. For the present analysis, patients were grouped according to the presence of reported symptoms (i.e., headache; anosmia and ageusia; syncope and dizziness) vs. clinically-diagnosed neurological manifestations (clinically-defined neurological syndrome: neurological signs or diagnoses captured by clinical evaluation) and matched with patients without neurological manifestations by age, sex, number of comorbidities, hospital of admission, and whether or not patients had underlying neurological disease., Results: From 6,635 hospitalized patients with COVID-19, 30.8% presented reported neurological manifestations, 10.3% were diagnosed with a neurological syndrome and 60.1% did not show any neurological manifestations. In patients with reported symptoms, the most common ones were headache (20.7%), ageusia (11.1%) and anosmia (8.0%). In patients with neurological syndromes, acute encephalopathy was the most common diagnosis (9.7%). In the matched analysis, patients with neurological syndromes presented more cases of septic shock (17.0 vs. 13.0%, p = 0.045), intensive care unit admission (45.3 vs. 38.9%, p = 0.023), and mortality (38.7 vs. 32.6%, p = 0.026; and 39.2 vs. 30.3%, p < 0.001) when compared to controls., Conclusion: COVID-19 in-hospital patients with clinically defined neurological syndromes presented a higher incidence of septic shock, ICU admission and death when compared to controls., Competing Interests: Declaration of Competing Interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2022. Published by Elsevier B.V.)

Background and Purpose: Clinical outcomes of multiple sclerosis (MS) patients affected by coronavirus disease 2019 (COVID-19) have been thoroughly investigated, but a further analysis on main signs and symptoms and their risk factors still needs attention. The objective of this study was to group together and describe based on similarity the most common signs and symptoms of COVID-19 in MS patients and identify all factors associated with their manifestation., Method: Logistic and linear regression models were run to recognize factors associated with each pooled group of symptoms and their total number., Results: From March 2020 to November 2021, data were collected from 1354 MS patients with confirmed infection of COVID-19. Ageusia and anosmia was less frequent in older people (odds ratio [OR] 0.98; p = 0.005) and more in smoker patients (OR 1.39; p = 0.049). Smoke was also associated with an incremental number of symptoms (OR 1.24; p = 0.031), substance abuse (drugs or alcohol), conjunctivitis and rash (OR 5.20; p = 0.042) and the presence of at least one comorbidity with shortness of breath, tachycardia or chest pain (OR 1.24; p = 0.008). Some disease-modifying therapies were associated with greater frequencies of certain COVID-19 symptoms (association between anti-CD20 therapies and increment in the number of concomitant symptoms: OR 1.29; p = 0.05). Differences in frequencies between the three waves were found for flu-like symptoms (G1, p = 0.024), joint or muscle pain (G2, p = 0.013) and ageusia and anosmia (G5, p &lt; 0.001). All cases should be referred to variants up to Delta., Conclusion: Several factors along with the choice of specific therapeutic approaches might have a different impact on the occurrence of some COVID-19 symptoms., (© 2022 European Academy of Neurology.)

Introduction: Anosmia and hypogeusia are frequent symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in adults, but their incidence in children is unknown., Objective: Describe the incidence and associated characteristics of olfactory and gustatory dysfunction in children with SARS-CoV-2 infection., Material and Methods: Descriptive study carried out by telephone survey of patients aged between five and 18 years with SARS-CoV-2 infection confirmed between March and December, 2020., Results: Two hundred eighty Spanish patients (female: 42.2%) with a mean age of 10.4 years (±3.54, range: 5 to 17) were analyzed, 22.5% with other diseases (mostly respiratory: 11.8%). The most frequent symptoms were fever (55.36%) and neurological symptoms (45.7%). Forty-four (15.7%) were hospitalized due to the infection, in intensive care unit (ICU): 7.1%. Forty-five patients (16.1%) had anosmia and/or hypogeusia: 32 both, eight with hypogeusia only, and five with exclusively anosmia. The mean symptom duration in days for anosmia was 36.4, and for hypogeusia it was 27.6. Either symptom was the initial manifestation in 15 patients. None had anosmia/hypogeusia with no other symptoms. Anosmia/hypogeusia was related to the presence of respiratory infection, gastroenteritis, chills, odynophagia, myalgia, asthenia, and anorexia, but not severity (hospitalization/ICU admission). Cohabitation with another infected individual was associated with a higher incidence of anosmia/hypogeusia (P = 0.041) and duration of anosmia (P = 0.006). The presence of anosmia/hypogeusia in cohabitants was associated with longer duration of anosmia (P < 0.001)., Conclusions: The incidence of anosmia/hypogeusia in children with SARS-CoV-2 was lower than that reported in adults, although with a longer duration. Although no association was found between anosmia/hypogeusia and greater disease severity, recognition of these symptoms could help identify paucisymptomatic patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

BACKGROUND Endotracheal intubation is an essential procedure to protect the airway. However, immediate complications like voice hoarseness, cervical spine injury, and tooth trauma are common. One of the rarest complications is lingual nerve palsy. Risk factors include small airway instruments, non-supine position, nitrous oxide use, and difficult intubation. Only 15 cases of lingual nerve injury were identified worldwide, and only 2 of them were bilateral. This case report describes the third case of bilateral lingual nerve palsy after intubation. CASE REPORT We present a 52-year-old woman admitted for a total abdominal hysterectomy. Postoperatively, the patient noted voice hoarseness, left tongue numbness, and loss of taste on both sides of the tongue. MRI brain revealed no new masses or lesions, and a diagnosis of bilateral lingual nerve palsy was made. She was treated conservatively with symptom observation for 14 weeks. On follow-up, she remained with only a patch of numbness and dryness, and loss of taste on the top middle area of the tongue. CONCLUSIONS Lingual nerve palsy is a very rare but devastating adverse effect of airway manipulation. Symptoms can include dryness, loss of sensation, and loss of taste of the anterior two-thirds of the tongue on the ipsilateral side. Salivary function assessment is important to determine the location of peripheral nerve injury. All possible causes like stroke, hemorrhage, and nerve impingement should be evaluated. MRI is advised to exclude central etiologies. Steroids may be used to decrease tissue edema and inflammation.

In early 2020, one of the most prevalent symptoms of SARS-CoV-2 infection was the loss of smell (anosmia), found in 60-70% of all cases. Anosmia used to occur early, concomitantly with other symptoms, and often persisted after recovery for an extended period, sometimes for months. In addition to smell disturbance, COVID-19 has also been associated with loss of taste (ageusia). The latest research suggests that SARS-CoV-2 could spread from the respiratory system to the brain through receptors in sustentacular cells localized to the olfactory epithelium. The virus invades human cells via the obligatory receptor, angiotensin-converting enzyme II (ACE2), and a priming protease, TMPRSS2, facilitating viral penetration. There is an abundant expression of both ACE2 and TMPRSS2 in sustentacular cells. In this study, we evaluated 102 COVID-19 hospitalized patients, of which 17.60% presented anosmia and 9.80% ageusia. ACE1 , ACE2 , and TMPRSS2 gene expression levels in nasopharyngeal tissue were obtained by RT-qPCR and measured using ΔCT analysis. ACE1 Alu 287bp association was also evaluated. Logistic regression models were generated to estimate the effects of variables on ageusia and anosmia Association of ACE2 expression levels with ageusia. was observed (OR: 1.35; 95% CI: 1.098-1.775); however, no association was observed between TMPRSS2 and ACE1 expression levels and ageusia. No association was observed among the three genes and anosmia, and the Alu 287bp polymorphism was not associated with any of the outcomes. Lastly, we discuss whetherthere is a bridge linking these initial symptoms, including molecular factors, to long-term COVID-19 health consequences such as cognitive dysfunctions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Braga-Paz, Ferreira de Araújo, Alves, de Ávila, Resende, Teixeira, de Aguiar, de Souza and Bahia.)

Competing Interests: Competing interests: Please see research paper for full details of researcher’s COIs. CK is the founder of AbScent, a non-profit patient support group for people with olfactory dysfunction.

Objective Based on the increasing incidence of smell and taste dysfunction among coronavirus disease 2019 (COVID-19) patients, such issues have been considered an early symptom of infection. However, few studies have investigated the type of taste components that are most frequently affected in COVID-19 patients. This study investigated the difference in frequencies of the types of taste component disorders among hospitalized COVID-19 patients. Methods In this retrospective, single-center, observational study, patients' background characteristics, clinical course, laboratory and radiological findings, and details on taste and/or smell disorders were collected and analyzed from medical records. Patients A total of 227 COVID-19 patients were enrolled, among whom 92 (40.5%) complained of taste disorders. Results Multiple types of taste disorders (hypogeusia/ageusia and hypersensitivity, or hypersensitivity and changing tastes) were reported in 10 patients. In particular, 23 patients reported hypersensitivity to at least 1 type of taste, and 2 patients complained of a bitter taste on consuming sweet foods. Impairment of all taste components was found in 48 patients (52.2%). The most frequent taste disorder was salty taste disorder (81 patients, 89.0%). Hypersensitivity to salty taste was most frequently observed (19 patients, 20.9%). Conclusion Patients with COVID-19 develop multiple types of taste disorders, among which salty taste disorder was the most frequent, with many patients developing hypersensitivity to salty taste. As smell and taste are subjective senses, further studies with the combined use of objective examinations will be required to confirm the findings.

We analyzed symptoms and comorbidities as predictors of hospitalization in 710 outpatients in North-East Germany with PCR-confirmed SARS-CoV-2 infection. During the first 3 days of infection, commonly reported symptoms were fatigue (71.8%), arthralgia/myalgia (56.8%), headache (55.1%), and dry cough (51.8%). Loss of smell (anosmia), loss of taste (ageusia), dyspnea, and productive cough were reported with an onset of 4 days. Anosmia or ageusia were reported by only 18% of the participants at day one, but up to 49% between days 7 and 9. Not all participants who reported ageusia also reported anosmia. Individuals suffering from ageusia without anosmia were at highest risk of hospitalization (OR 6.8, 95% CI 2.5-18.1). They also experienced more commonly dyspnea and nausea (OR of 3.0, 2.9, respectively) suggesting pathophysiological connections between these symptoms. Other symptoms significantly associated with increased risk of hospitalization were dyspnea, vomiting, and fever. Among basic parameters and comorbidities, age > 60 years, COPD, prior stroke, diabetes, kidney and cardiac diseases were also associated with increased risk of hospitalization. In conclusion, due to the delayed onset, ageusia and anosmia may be of limited use in differential diagnosis of SARS-CoV-2. However, differentiation between ageusia and anosmia may be useful for evaluating risk for hospitalization., (© 2022. The Author(s).)

BACKGROUND Myasthenia gravis (MG) is an autoimmune neuromuscular disorder, which is often accompanied by various complications. Partial dysgeusia is an uncommon nonmotor symptom of MG, and dysgeusia preceding typical MG symptoms is rare. Although ageusia and hypogeusia have been reported in patients with MG, increased perception of taste has not been reported. CASE REPORT A 47-year-old Japanese woman presented with a reduced perception of sweet taste and an increased perception of salty taste. Meanwhile, she was diagnosed with thymoma-associated generalized MG and underwent extended thymectomy. Three months later, her anti-acetylcholine receptor (AChR) antibody (Ab) titer increased to 70 nmol/L, when she had completely lost perception of sweet taste and had developed a markedly increased perception of salty taste. Prednisolone and tacrolimus were then added to the medication, and her partial dysgeusia gradually improved. As the AChR Ab titer decreased, disturbance of sweet taste resolved, although a slight decrease persisted. The increased perception of salty taste returned to normal. CONCLUSIONS This is a rare case of a patient with MG who developed an increased salty taste perception with a reduced sweet taste perception 3 months before the onset of her motor symptoms. We suggest that MG should be considered as a differential diagnosis in patients with partial dysgeusia but no motor symptoms.

Objective: The aim of this research was to determine the relationship and prevalence of taste and smell dysfunction in patients with COVID-19 in the United Arab Emirates (UAE) population., Methods: Enrolled participants were interviewed online via a phone call after obtaining their informed consent. Quantification of smell, taste, and other sensations before, during, and after COVID-19 infection was correlated with the severity of COVID-19 symptoms., Results: A total of 500 patients with (mild-severe) COVID-19 completed the survey. A total of 26.4% were asymptomatic, and 21.4% were classified as paucisymptomatic with less severe symptoms. Almost equal proportions of the studied population experienced extreme taste sensation reductions (43%) and loss of smell sensation (44%). Statistically significant drastic decreases in smell and taste senses were seen among younger individuals. The magnitude of reduction in both sense changes increased steeply from the asymptomatic group to the paucisymptomatic group to the symptomatic group., Conclusions: Sudden anosmia or ageusia need to be recognised for early detection of COVID-19 infection to identify otherwise hidden carriers, thus favoring an early isolation strategy that will restrict the spread of the disease., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Limited information is available regarding real-world treatment patterns and their effectiveness and safety in patients with locally advanced basal cell carcinoma, including patients not typically represented in clinical trials. The purpose of the current study was to describe how clinicians diagnose and treat locally advanced basal cell carcinoma in the United States., Methods: This prospective, multicenter, observational registry study included patients with newly diagnosed, Hedgehog pathway inhibitor-naive locally advanced basal cell carcinoma without basal cell carcinoma nevus syndrome (n = 433) treated at 75 US academic and community practices, including dermatology, Mohs surgery, and medical oncology sites. The main outcomes of this study were treatment patterns and associated effectiveness and safety for patients with locally advanced basal cell carcinoma in real-world settings., Results: Determination of locally advanced basal cell carcinoma was mainly based on lesion size (79.6% of patients), histopathology (54.3%), extent of involvement (49.0%), and location (46.2%). Within 90 days of determination of locally advanced disease, 115 patients (26.6%) received vismodegib, 251 (58.0%) received surgery/other (non-vismodegib) treatment, and 67 (15.5%) had not yet received treatment (observation). Vismodegib-treated patients had a higher prevalence of high-risk clinical features predictive for locoregional recurrence than those with non-vismodegib treatment or observation. Clinical response rate was 85.1% with vismodegib and 94.9% with non-vismodegib treatment (primarily surgery). The most common adverse events with vismodegib were ageusia/dysgeusia, muscle spasms, alopecia, and weight loss. Rates of cutaneous squamous cell cancers were comparable between vismodegib and non-vismodegib treatment., Conclusions: This prospective observational study offers insight on real-world practice, treatment selection, and outcomes for a nationally representative sample of US patients with locally advanced basal cell carcinoma. For patients with lesions that were not amenable to surgery, vismodegib treatment was associated with effectiveness and safety that was consistent with that observed in clinical trials., Competing Interests: A. Sekulic has no conflict of interest to declare. S. Yoo has no conflict of interest to declare. R. Kudchadkar has served on advisory boards and received honoraria from Bristol Myers Squibb and has received grants/research funding from Merck. J. Guillen has no conflict of interest to declare. G. Rogers has no conflict of interest to declare. A.L.S. Chang has served as a clinical investigator for research studies funded by Roche/Genentech, Merck, Novartis, and Regeneron. S. Guenthner has served on advisory boards and received grants/research funding and honoraria from Genentech, Pfizer, AbbVie, Amgen, LEO Pharma, Lilly, Dermira, Sun Pharma, UCB, Vanda, and Janssen. B. Raskin has no conflict of interest to declare. K. Dawson, Y. Mun, L. Chu, and E. McKenna are employees of Genentech and hold stock/stock options in Roche/Genentech. M. Lacouture has received royalties from Legacy Healthcare Services, Apricity Health, Azitra, Deciphera, Galderma, Johnson & Johnson, NCODA, Novocure, Kyowa Kirin, Loxo, Merck Sharp & Dohme, Janssen, Menlo Therapeutics, Novartis, QED Therapeutics, F. Hoffmann-La Roche, Amgen, AstraZeneca, Genentech, Seagen, Lutris, Paxman Collers, OnQuality Pharmaceuticals, and Takeda Millennium and has received research funding from Veloce, US Biotest, Lutris, Paxman, and Novocure.

Objective: Craniopharyngiomas (CPs) are benign, dysontogenetic tumors associated with complex endocrinologic and neurologic symptoms and high morbidity. The aim of this study is to elucidate modifiable effectors of health-related quality of life (HrQoL) of adult patients with CP following neurosurgical intervention using standardized instruments as well as descriptive analysis., Methods: HrQoL (European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 and BN20) was evaluated in 20 adult patients with CP. We examined pre- as well as postoperative radiologic, hormonal, and symptom-oriented data in a retrospective analysis. Surgical approach, postoperative complications, and extent of resection were recorded. Additional descriptive analysis was performed on case records of all patients with HrQoL results., Results: Long-term follow-up of HrQoL (mean of 75 months) was lower than the in healthy reference group (CP = 58, reference = 75). The most common postoperative complaints were endocrinologic disturbances (88%). Overall, univariate and multivariate logistic regression analysis revealed no significant predictors of reduced postoperative HrQoL. Descriptive analysis did, however, reveal a cluster of patients among those with the lowest global HrQoL which reported new postoperative anosmia and ageusia., Conclusions: The global HrQoL of our cohort showed a substantial reduction compared with a healthy reference population. Postoperative hyposmia and ageusia is found in patients with the lowest postoperative HrQoL who otherwise had no new significant endocrinologic or neurologic complications. As these symptoms are not regularly accounted for in the HrQoL instruments used in this study, further analysis is needed to determine the possible significance of this complication in CP surgery, and it may affect the choice of surgical approach as well as the information patients receive before consenting to surgery., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Rapid detection, isolation, and contact tracing of community COVID-19 cases are essential measures to limit the community spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to identify a parsimonious set of symptoms that jointly predict COVID-19 and investigated whether predictive symptoms differ between the B.1.1.7 (Alpha) lineage (predominating as of April 2021 in the US, UK, and elsewhere) and wild type., Methods and Findings: We obtained throat and nose swabs with valid SARS-CoV-2 PCR test results from 1,147,370 volunteers aged 5 years and above (6,450 positive cases) in the REal-time Assessment of Community Transmission-1 (REACT-1) study. This study involved repeated community-based random surveys of prevalence in England (study rounds 2 to 8, June 2020 to January 2021, response rates 22%-27%). Participants were asked about symptoms occurring in the week prior to testing. Viral genome sequencing was carried out for PCR-positive samples with N-gene cycle threshold value < 34 (N = 1,079) in round 8 (January 2021). In univariate analysis, all 26 surveyed symptoms were associated with PCR positivity compared with non-symptomatic people. Stability selection (1,000 penalized logistic regression models with 50% subsampling) among people reporting at least 1 symptom identified 7 symptoms as jointly and positively predictive of PCR positivity in rounds 2-7 (June to December 2020): loss or change of sense of smell, loss or change of sense of taste, fever, new persistent cough, chills, appetite loss, and muscle aches. The resulting model (rounds 2-7) predicted PCR positivity in round 8 with area under the curve (AUC) of 0.77. The same 7 symptoms were selected as jointly predictive of B.1.1.7 infection in round 8, although when comparing B.1.1.7 with wild type, new persistent cough and sore throat were more predictive of B.1.1.7 infection while loss or change of sense of smell was more predictive of the wild type. The main limitations of our study are (i) potential participation bias despite random sampling of named individuals from the National Health Service register and weighting designed to achieve a representative sample of the population of England and (ii) the necessary reliance on self-reported symptoms, which may be prone to recall bias and may therefore lead to biased estimates of symptom prevalence in England., Conclusions: Where testing capacity is limited, it is important to use tests in the most efficient way possible. We identified a set of 7 symptoms that, when considered together, maximize detection of COVID-19 in the community, including infection with the B.1.1.7 lineage., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: PE is the director of the MRC Centre of Environment and Health (MR/L01341X/1 and MC/S019669/1) and has no conflict of interest to disclose. M C-H holds shares in the O-SMOSE company and has no conflict of interest to disclose. Consulting activities conducted by the company are independent of the present work. All other authors have no conflict of interest to disclose.

Background: Multiple voluntary surveillance platforms were developed across the world in response to the COVID-19 pandemic, providing a real-time understanding of population-based COVID-19 epidemiology. During this time, testing criteria broadened and health-care policies matured. We aimed to test whether there were consistent associations of symptoms with SARS-CoV-2 test status across three surveillance platforms in three countries (two platforms per country), during periods of testing and policy changes., Methods: For this observational study, we used data of observations from three volunteer COVID-19 digital surveillance platforms (Carnegie Mellon University and University of Maryland Facebook COVID-19 Symptom Survey, ZOE COVID Symptom Study app, and the Corona Israel study) targeting communities in three countries (Israel, the UK, and the USA; two platforms per country). The study population included adult respondents (age 18-100 years at baseline) who were not health-care workers. We did logistic regression of self-reported symptoms on self-reported SARS-CoV-2 test status (positive or negative), adjusted for age and sex, in each of the study cohorts. We compared odds ratios (ORs) across platforms and countries, and we did meta-analyses assuming a random effects model. We also evaluated testing policy changes, COVID-19 incidence, and time scales of duration of symptoms and symptom-to-test time., Findings: Between April 1 and July 31, 2020, 514 459 tests from over 10 million respondents were recorded in the six surveillance platform datasets. Anosmia-ageusia was the strongest, most consistent symptom associated with a positive COVID-19 test (robust aggregated rank one, meta-analysed random effects OR 16·96, 95% CI 13·13-21·92). Fever (rank two, 6·45, 4·25-9·81), shortness of breath (rank three, 4·69, 3·14-7·01), and cough (rank four, 4·29, 3·13-5·88) were also highly associated with test positivity. The association of symptoms with test status varied by duration of illness, timing of the test, and broader test criteria, as well as over time, by country, and by platform., Interpretation: The strong association of anosmia-ageusia with self-reported positive SARS-CoV-2 test was consistently observed, supporting its validity as a reliable COVID-19 signal, regardless of the participatory surveillance platform, country, phase of illness, or testing policy. These findings show that associations between COVID-19 symptoms and test positivity ranked similarly in a wide range of scenarios. Anosmia, fever, and respiratory symptoms consistently had the strongest effect estimates and were the most appropriate empirical signals for symptom-based public health surveillance in areas with insufficient testing or benchmarking capacity. Collaborative syndromic surveillance could enhance real-time epidemiological investigations and public health utility globally., Funding: National Institutes of Health, National Institute for Health Research, Alzheimer's Society, Wellcome Trust, and Massachusetts Consortium on Pathogen Readiness., Competing Interests: Declaration of interests ZOE Global codeveloped the app pro bono for non-commercial purposes. JW, JCP, and SG work for ZOE Global, and TDS is a consultant for ZOE Global. LHN, DAD, and ATC previously participated as investigators on a diet study unrelated to this work, which was supported by ZOE Global. ATC reports personal fees from Pfizer, Bayer Pharma, and Boehringer Ingelheim, outside the submitted work. All other authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: This investigation aimed to assess the effect of smoking on the onset and resolution of dysgeusia/hypogeusia in head and neck cancer (HNC) patients receiving radiotherapy (XRT)., Materials and Methods: This is a retrospective cohort investigation of HNC patients treated with XRT. Data collected from the patients' medical records included demographics, primary cancer diagnoses, HNC therapeutic modalities, smoking status, and dates of onset/resolution of dysgeusia/hypogeusia., Results: A 103 met inclusion criteria, of which 61.8% developed dysgeusia/hypogeusia. Mean age was 58.3 ± 12.9 and 66% were either former or current smokers. Never smokers seemed to be at higher, but statistically insignificant, the risk for developing dysgeusia/hypogeusia than former or current smokers [HR 1.05 and 1.66; 95% CI (0.60, 1.84) and (0.85, 3.24)]. They were also less likely to recover when compared to former smokers [HR 0.74; 95% CI (0.39, 1.39)]. Although statistically insignificant, never smokers showed rapid dysgeusia/hypogeusia onset after XRT compared to former or current smokers (median 14 days versus 22 and 9 days, respectively; p = 0.25). Never smokers showed quicker but statistically insignificant, recovery time compared to former or current smokers (median 113 days versus 149 and 238 days, respectively; p = 0.57)., Conclusion: Although results lacked statistical significance, never smokers receiving XRT were prone to higher risk and faster onset of dysgeusia/hypogeusia than former and current smokers.

In the DECODE project, data were collected from 3,114 surveys filled by symptomatic patients RT-qPCR tested for SARS-CoV-2 in a single university centre in March-September 2020. The population demonstrated balanced sex and age with 759 SARS-CoV-2( +) patients. The most discriminative symptoms in SARS-CoV-2( +) patients at early infection stage were loss of taste/smell (OR = 3.33, p < 0.0001), body temperature above 38℃ (OR = 1.67, p < 0.0001), muscle aches (OR = 1.30, p = 0.0242), headache (OR = 1.27, p = 0.0405), cough (OR = 1.26, p = 0.0477). Dyspnea was more often reported among SARS-CoV-2(-) (OR = 0.55, p < 0.0001). Cough and dyspnea were 3.5 times more frequent among SARS-CoV-2(-) (OR = 0.28, p < 0.0001). Co-occurrence of cough, muscle aches, headache, loss of taste/smell (OR = 4.72, p = 0.0015) appeared significant, although co-occurrence of two symptoms only, cough and loss of smell or taste, means OR = 2.49 (p < 0.0001). Temperature > 38℃ with cough was most frequent in men (20%), while loss of taste/smell with cough in women (17%). For younger people, taste/smell impairment is sufficient to characterise infection, whereas in older patients co-occurrence of fever and cough is necessary. The presented study objectifies the single symptoms and interactions significance in COVID-19 diagnoses and demonstrates diverse symptomatology in patient groups.

Background: The cutaneous manifestations of coronavirus disease 2019 (COVID-19) have been covered insufficiently in the literature., Methods: Thirty-nine patients admitted to the study hospital with confirmed COVID-19 who experienced various skin manifestations during hospitalization or in the convalescence period, were analysed retrospectively., Results: Thirty-nine patients with COVID-19, admitted to the study hospital between 23 March and 12 September 2020, had intra-infectious rash or lesions of cutaneous vasculitis during convalescence. The most common cutaneous manifestations of COVID-19 were erythematous and erythematous papular rash. Twenty-seven of the 39 patients had anosmia (69.2%), 26 patients had ageusia (66.7%), 34 patients had pneumonia (87.2%) and 24 patients had intra-infectious enterocolitis (61.5%). Skin biopsies were rarely performed in these patients. This article reports the results of biopsies performed in two patients, showing histopathological and immunohistochemical changes in erythematous rash and erythema multiforme-like lesions. Both skin biopsies revealed early fibrous remodelling of the dermis, suggesting similarity with changes that occur in the lungs and other tissues in patients with COVID-19., Conclusions: Correlations between skin lesions and anosmia, ageusia and enteritis in patients with COVID-19 do not seem to be accidental, but are associated with a similar response to ACE2 receptor expression in these tissues., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Olfactory dysfunction is relatively high in coronavirus disease 2019 (COVID-19) patients. The aim of this study is to investigate the incidence of olfactory disorder objectively in patients with laboratory-confirmed COVID-19 infection., Material and Method: The study included 31 healthy controls and 59 COVID-19 patients who were diagnosed and treated in the COVID departments in a tertiary hospital. The patients with corona virus infection were screened by a questionnaire and were classified into 2 groups as either group 2 (patients without self-reported smell loss) or group 3 (patients with self-reported smell loss). Age and gender matched healthy controls who do not have chronic nasal condition or nasal surgery history comprised the control group (group 1). All of the patients and subjects in the control group were tested by the Sniffin' Sticks test. All of the answers and scores were recorded, and the comparisons were made., Results: The rate of self-reported smell and taste loss in all COVID-19 patients in this study was 52.5% and 42%, respectively. There was a significant difference in threshold, discrimination, identification, and Threshold, Discrimination, Identification (TDI) scores between groups 1 and 2. When the comparisons between group 1 and 3 were made, again threshold, discrimination, identification, and TDI scores were significantly different. The comparison between groups 2 and 3 demonstrated a significant difference in discrimination, identification, and TDI scores, but threshold score was not different statistically. With questionnaire, the rate of olfactory dysfunction in COVID-19 patients was 52.5%, but with objective test, the rate was calculated as 83%., Conclusion: Olfactory and gustatory dysfunctions are common in COVID-19 patients. According to findings with the objective test method in this study, smell disorder in COVID-19 patients was much higher than those detected by questionnaires.

Objective: To determine taste and smell impairment rates in patients with coronavirus disease 2019 (COVID-19) who were hospitalized in the intensive care unit (ICU)., Methods: Between March 2020 and May 2020, patients with COVID-19 hospitalized in the ICU were enrolled in this study. Upon discharge, patients were telephoned and asked to complete a survey related to taste and smell impairment. Characteristics were compared between patients with and without taste and/or smell impairment., Results: Fifty-two patients were enrolled (mean age, 61.32 ± 12.53 years; mean ICU stay, 10.19 ± 10.24 days). Age, sex, type/number of comorbid diseases, most ICU support modalities, and ICU stay duration did not significantly differ between groups. Patients in group B required more high-flow nasal oxygen therapy than patients in group A ( P = .010). In total, 22 (42.3%) of 52 patients experienced taste and/or smell impairment. Three patients experienced isolated smell impairment and one patient experienced isolated taste impairment. Among the 21 patients who experienced smell impairment, 18 (85.78%) experienced hyposmia (mean visual analog scale [VAS] score: 6.33 ± 0.97), while 3 (14.28%) experienced anosmia. Among the 19 patients who experienced taste impairment, 16 (84.22%) experienced hypogeusia (mean VAS score: 6.43 ± 1.03) and 3 (15.78%) experienced ageuisa. Among 22 patients who experienced taste and/or smell impairment, 15 (68.18%) patients (n = 15/22) experienced smell and/or taste impairment before the ICU stay, while 7 (31.82%) patients (n = 7/22) experienced impairment during the ICU stay. Overall, 28.84% (n = 15/52) of the patients experienced taste and/or smell impairment before the ICU stay., Conclusions: Patients who were hospitalized in the ICU experienced lower rates of taste and/or smell impairment. Some patients experienced taste and/or smell impairment during the ICU stay.

COVID-19 disease induced by coronavirus SARS-CoV-2 presents among its symptoms alterations of the chemosensory functions. In the first studies on the Chinese population, this symptomatology was not particularly relevant, and hyposmia and hypogeusia were excluded from the symptoms to be evaluated to diagnose the disease. With the pandemic spread of the illness, there has been an augment in reports on chemosensory dysfunctions among patients. The first data analysis showed the presence of these disorders mainly in paucisymptomatic and asymptomatic patients. The interest in chemosensory systems therefore increased considerably, because the olfactory and gustatory symptoms could be the key to stop the infection spread. Furthermore, the degree of alert and attention grew, considering that these types of dysfunctions are prognostic symptoms of serious neurodegenerative diseases. About 9 months have passed since the first anecdotal reports on the involvement of the olfactory and gustatory systems in the COVID-19 pathology. For this reason, a careful review of the literature was conducted to understand if it is clearer which people present chemosensory symptoms and if these are related to the severity of the disease. Furthermore, we have identified which aspects still remain to be clarified.

Background: Loss of smell and/or taste are cardinal symptoms of COVID-19. 'Long-COVID', persistence of symptoms, affects around one fifth of people. However, data regarding the clinical resolution of loss of smell and/or taste are lacking. In this study we assess smell and taste loss resolution at 4-6 week follow-up, aim to identify risk factors for persistent smell loss and describe smell loss as a feature of long-COVID in a community cohort in London with known SARS-CoV-2 IgG/IgM antibody status. We also compare subjective and objective smell assessments in a subset of participants., Methods: Four hundred sixty-seven participants with acute loss of smell and/or taste who had undergone SARS-CoV-2 IgG/IgM antibody testing 4-6 weeks earlier completed a follow-up questionnaire about resolution of their symptoms. A subsample of 50 participants completed an objective olfactory test and results were compared to subjective smell evaluations., Results: People with SARS-CoV-2 antibodies with an acute loss of sense of smell and taste were significantly less likely to recover their sense of smell/taste than people who were seronegative (smell recovery: 57.7% vs. 72.1%, p = 0.027. taste recovery 66.2% vs. 80.3%, p = 0.017). In SARS-CoV-2 positive participants, a higher percentage of male participants reported full resolution of smell loss (72.8% vs. 51.4%; p < 0.001) compared to female participants, who were almost 2.5-times more likely to have ongoing smell loss after 4-6 weeks (OR 2.46, 95%CI 1.47-4.13, p = 0.001). Female participants with SARS-CoV-2 antibodies and unresolved smell loss and unresolved taste loss were significantly older (> 40 years) than those who reported full resolution. Participants who experienced parosmia reported lower smell recovery rates and participants with distorted taste perception lower taste recovery rates. Parosmia had a significant association to unresolved smell loss (OR 2.47, 95%CI 1.54-4.00, p < 0.001)., Conclusion: Although smell and/or taste loss are often transient manifestations of COVID-19, 42% of participants had ongoing loss of smell, 34% loss of taste and 36% loss of smell and taste at 4-6 weeks follow-up, which constitute symptoms of 'long-COVID'. Females (particularly > 40 years) and people with a distorted perception of their sense of smell/taste are likely to benefit from prioritised early therapeutic interventions., Trials Registration: ClinicalTrials.gov NCT04377815 Date of registration: 23/04/2020.

Background: The clinical implications of SARS-CoV-2 infection are highly variable. Some people with SARS-CoV-2 infection remain asymptomatic, whilst the infection can cause mild to moderate COVID-19 and COVID-19 pneumonia in others. This can lead to some people requiring intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever, cough, or loss of smell or taste, and signs such as oxygen saturation are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19, or select patients for further testing. This is an update of this review, the first version of which published in July 2020., Objectives: To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19., Search Methods: For this review iteration we undertook electronic searches up to 15 July 2020 in the Cochrane COVID-19 Study Register and the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions., Selection Criteria: Studies were eligible if they included patients with clinically suspected COVID-19, or if they recruited known cases with COVID-19 and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies in hospitalised patients were only included if symptoms and signs were recorded on admission or at presentation. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards., Data Collection and Analysis: Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary studies were available, and whenever heterogeneity across studies was deemed acceptable., Main Results: We identified 44 studies including 26,884 participants in total. Prevalence of COVID-19 varied from 3% to 71% with a median of 21%. There were three studies from primary care settings (1824 participants), nine studies from outpatient testing centres (10,717 participants), 12 studies performed in hospital outpatient wards (5061 participants), seven studies in hospitalised patients (1048 participants), 10 studies in the emergency department (3173 participants), and three studies in which the setting was not specified (5061 participants). The studies did not clearly distinguish mild from severe COVID-19, so we present the results for all disease severities together. Fifteen studies had a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. This may have especially influenced the sensitivity of those features used in referral protocols, such as fever and cough. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional 12 studies, we were unable to assess the risk for selection bias. This makes it very difficult to judge the validity of the diagnostic accuracy of the signs and symptoms from these included studies. The applicability of the results of this review update improved in comparison with the original review. A greater proportion of studies included participants who presented to outpatient settings, which is where the majority of clinical assessments for COVID-19 take place. However, still none of the studies presented any data on children separately, and only one focused specifically on older adults. We found data on 84 signs and symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. Only cough (25 studies) and fever (7 studies) had a pooled sensitivity of at least 50% but specificities were moderate to low. Cough had a sensitivity of 67.4% (95% confidence interval (CI) 59.8% to 74.1%) and specificity of 35.0% (95% CI 28.7% to 41.9%). Fever had a sensitivity of 53.8% (95% CI 35.0% to 71.7%) and a specificity of 67.4% (95% CI 53.3% to 78.9%). The pooled positive likelihood ratio of cough was only 1.04 (95% CI 0.97 to 1.11) and that of fever 1.65 (95% CI 1.41 to 1.93). Anosmia alone (11 studies), ageusia alone (6 studies), and anosmia or ageusia (6 studies) had sensitivities below 50% but specificities over 90%. Anosmia had a pooled sensitivity of 28.0% (95% CI 17.7% to 41.3%) and a specificity of 93.4% (95% CI 88.3% to 96.4%). Ageusia had a pooled sensitivity of 24.8% (95% CI 12.4% to 43.5%) and a specificity of 91.4% (95% CI 81.3% to 96.3%). Anosmia or ageusia had a pooled sensitivity of 41.0% (95% CI 27.0% to 56.6%) and a specificity of 90.5% (95% CI 81.2% to 95.4%). The pooled positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.25 (95% CI 3.17 to 5.71) and 4.31 (95% CI 3.00 to 6.18) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The pooled positive likelihood ratio of ageusia alone was only 2.88 (95% CI 2.02 to 4.09). Only two studies assessed combinations of different signs and symptoms, mostly combining fever and cough with other symptoms. These combinations had a specificity above 80%, but at the cost of very low sensitivity (< 30%)., Authors' Conclusions: The majority of individual signs and symptoms included in this review appear to have very poor diagnostic accuracy, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out COVID-19. The presence of anosmia or ageusia may be useful as a red flag for COVID-19. The presence of fever or cough, given their high sensitivities, may also be useful to identify people for further testing. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19, are still urgently needed. Results from such studies could inform subsequent management decisions., (Copyright © 2021 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Objectives: To describe the clinical evolution and predictors of symptom persistence during 2 months' follow-up in adults with noncritical coronavirus disease 2019 (COVID-19)., Methods: We performed descriptive clinical follow-up (day (D) 7, D30 and D60) of 150 patients with noncritical COVID-19 confirmed by real-time reverse transcriptase PCR at Tours University Hospital from 17 March to 3 June 2020, including demographic, clinical and laboratory data collected from the electronic medical records and by phone call. Persisting symptoms were defined by the presence at D30 or D60 of at least one of the following: weight loss ≥5%, severe dyspnoea or asthenia, chest pain, palpitations, anosmia/ageusia, headache, cutaneous signs, arthralgia, myalgia, digestive disorders, fever or sick leave., Results: At D30, 68% (103/150) of patients had at least one symptom; and at D60, 66% (86/130) had symptoms, mainly anosmia/ageusia: 59% (89/150) at symptom onset, 28% (40/150) at D30 and 23% (29/130) at D60. Dyspnoea concerned 36.7% (55/150) patients at D30 and 30% (39/130) at D60. Half of the patients (74/150) at D30 and 40% (52/130) at D60 reported asthenia. Persistent symptoms at D60 were significantly associated with age 40 to 60 years old, hospital admission and abnormal auscultation at symptom onset. At D30, severe COVID-19 and/or dyspnoea at symptom onset were additional factors associated with persistent symptoms., Conclusions: Up to 2 months after symptom onset, two thirds of adults with noncritical COVID-19 had complaints, mainly anosmia/ageusia, dyspnoea or asthenia. A prolonged medical follow-up of patients with COVID-19 seems essential, whatever the initial clinical presentation., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: A wide range of neurological manifestations has been described in COVID-19., Methods: In this nationwide retrospective observational study, patients in Tunisia diagnosed with COVID-19 between the 2nd of March and the 16th of May 2020 were contacted by telephone. We collected demographic and clinical data and specified characteristics and evolution of main neurological symptoms., Results: Of 1034 confirmed COVID-19 patients, 646 were included (mean age 42.17 years old) and 466 (72.1%) had neurological symptoms. Neurological symptoms were isolated 22.7% (n = 106). Headache was the most frequent neurological symptom (n = 279, 41.1%): mainly frontotemporal (n = 143, 51.1%) and mild or moderate (n = 165, 59.1%). When associated with fever (n = 143, 51.3%), headache was more likely to be severe and present at onset. Recovery was reported in 83.2%. Smell and taste impairment were found in 37.9% (n = 245) and 36.8% (n = 238) respectively. Among them, 65.3% (156/239) were anosmic and 63.2% (146/231) were ageusic. A complete improvement was found in 72.1% (174/240) of smell impairment and in 76.8% (179/233) of taste impairment. Myalgia (n = 241, 37.3%) and sleep disturbances (n = 241, 37.3%) were also frequent. Imported cases had more neurological symptoms (p = 0.001). In 14.5%, neurological symptoms preceded the respiratory signs (RS). RS were associated with more frequent (p = 0.006) and numerous (p < 0.001) neurological symptoms., Conclusions: Neurological symptoms in COVID-19 are frequent, can be isolated and present at onset. A total recovery is the most recorded outcome. RS are predictive of neurological symptoms. Studies in to virus and host genetics should be considered to understand the different phenotypes.

Background: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations., Methods: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context., Results: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes., Conclusion: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.

Objective: The novel coronavirus disease-19 (COVID-19) pandemic had intense social and economic effects. Patients infected with COVID-19 may present with a series of conditions. A considerable number of patients express taste and smell disturbances as a prodromal, coexistent, or as the only manifestation of COVID-19 infection. The objective of the present review is to review the hypothetical mechanisms of action and etiopathogenesis of dysgeusia in COVID-19 patients., Materials and Methods: Multiple scientific databases were explored, including PubMed, Medline, Scopus, Cochrane-library, LILACS, Livivo and OpenGrey. All types of articles that discussed the pathogenesis of dysgeusia were included, while articles that described dysgeusia without detail about its mode of action were excluded., Results: A total of 47 articles, with different designs, were included in this review. These articles suggested direct viral neural invasion to olfactory and gustatory nerves, viral cytotoxicity to taste buds, angiotensin II imbalance, augmented pro-inflammatory cytokines, and disturbances in salivary glands and sialic acid. COVID-19 induced-dysgeusia was also associated with systemic diseases, medications, zinc, chemicals, and disinfectants., Conclusions: The most likely cause of transient dysgeusia in COVID-19 is peripheral neurotropism and direct toxicity to taste buds or olfactory epithelium. Other factors may also play a contributory role in dysgeusia, such as a defect in the quality and quantity of saliva, pro-inflammatory cytokines, angiotensin II accumulation, systemic diseases, hypozincemia, and excessive use of chemicals.

Smell loss is important for coronavirus disease-2019 (COVID-19) screening and diagnosis. Particular attention should be paid to individuals with pre-COVID-19 chronic hyposmia or anosmia. We report a case of reversible taste impairment in a COVID-19 patient with chronically impaired sense of smell. This case emphasizes the importance of COVID-19-related taste assessment.