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BACKGROUND: It has been reported worldwide that patients with a diagnosis of COVID-19 usually suffer a loss of smell and taste. In this study, we aimed to evaluate the relationship between the severity of the disease and the loss of smell and taste. In addition, we evaluated patients' smell and taste functions after recovery. METHODS: Between March and May 2020, 418 patients diagnosed with COVID-19 were divided into 3 groups: home-quarantined, hospitalized, and intensive care patients. The disease, smell, and taste functions of patients were evaluated with visual analog scores before diagnosis of COVID-19, during the disease, and fourth week after recovery. The types of smell loss and types of taste flavor loss occurring during the disease were questioned. RESULTS: In all 3 groups, changes in smell and taste loss during the disease were statistically detected (P = 0.001). The smell loss rates determined in groups 1 to 3 were 45%, 43.7%, and 31.2%, respectively. The taste loss rates determined in groups 1 to 3were 46.6%, 32.1%, and 31.2% respectively. The rate of patients with a total recovery of smell loss in groups 1 to 3 were 95.5%, 93.7%, and 100%, respectively (P = 0.768). The rate of patients with a total recovery of taste loss in groups 1 to 3 were 97.1%, 91.4%, and 100%, respectively (P = 0.423). CONCLUSION: COVID-19 causes significant loss of smell and taste in patients. The loss of smell and taste does not correlate with the severity of COVID-19 disease. The loss of smell and taste improves at a high rate after the disease.

Background COVID-19 is a syndrome caused by the recently emerged SARS-CoV-2. We collected clinical and epidemiologic data in an almost complete cohort of SARS-CoV-2 positive individuals from Regensburg, Germany, from March 2020 to May 2020. Methods Analysis of a retrospectively documented cohort of consecutive COVID-19 cases recorded between March 7, 2020 and May 24, 2020 as part of an infection control investigation program, with prospective follow-up interviews gathering information on type and duration of symptoms and COVID-19 risk factors until June 26, 2020. Results Of 1089 total cases, 1084 (99.5%) cases were included. The incidence during the time period was 315.4/100,000, lower than in the superordinate government district Oberpfalz (468.5/100,000) and the overall state of Bavaria (359.7/100,000). The case fatality ratio (CFR) was 2.1%. Among fatal cases, the mean age was 74.4 years and 87% presented with known risk factors, most commonly chronic heart disease, chronic lung disease, kidney disease, and diabetes mellitus. 897 cases (82.7%) showed at least one symptom, most frequently cough (45%) and fever (41%). Further, 18% of cases suffered from odour/taste disorder. 17% of total cases reported no symptoms. The median duration of general illness was 10 days. During follow-up, 8.9% of 419 interviewed cases reported at least one symptom lasting at least 6 weeks, and fatigue was the most frequent persistent symptom. Discussion We report data on type and duration of symptoms, and clinical severity of nearly all (99.5%) patients with SARS-CoV-2 recorded from March 2020 to May 2020 in Regensburg. A broad range of symptoms and symptom duration was seen, some of them lasting several weeks in a considerable number of cases. The case-fatality ratio was 2.1%. Asymptomatic cases may be underrepresented due to the nature of the study. Supplementary Information The online version of this article (10.1007/s15010-021-01580-2) contains supplementary material, which is available to authorized users.

Many patients with olfactory disorders were referred during the COVID-19 pandemic in 2020. The aim of this study was to detect outpatient cases with olfactory and taste disorders suspected to mild form of COVID-19 disease in Gorgan city in the north of Iran retrospectively. This study was performed on patients who had the complaints of olfactory disorders during 03/01/2020 to 04/01/2020. They also had the mild symptoms of upper respiratory tract infection. The control group included patients who had similar symptoms during this period but did not report olfactory or taste disturbances. Due to the limitations of serologic kits, this study was performed 2–3 months after the onset of symptoms. The number of patients and controls was 72 and 36 respectively. The range and the mean ± SD of patient’s age were 21–63 and 39.82 ± 9.82 years. In both groups, 44.44% were male and 55.56% were female. The time interval between the onset of symptoms and the serologic tests in both groups was 91.11 ± 16.20 days. In the cases and controls, the IgG titer was positive in 44.4% and 22.2% and the IgM titer was positive in 5.6% and 8.3% respectively. IgG antibody titers were higher in cases than in the control group (P = 0.024). There was no correlation among antibody titers and the severity of olfactory disturbances, the gender, and the age. The high COVID-19 IgG antibody titer in patients with olfactory disorder during the pandemic can probably be considered as a warning complaint of COVID-19 and may be used for isolation plans.

Taste disorders are common adverse effects of cancer chemotherapy that can reduce quality of life and impair nutritional status. However, the molecular mechanisms underlying chemotherapy-induced taste disorders remain largely unknown. Furthermore, there are no effective preventive measures for chemotherapy-induced taste disorders. We investigated the effects of a combination of three anticancer drugs (TPF: docetaxel, cisplatin and 5-fluorouracil) on the structure and function of mouse taste tissues and examined whether the drinking of ice-cold water after TPF administration would attenuate these effects. TPF administration significantly increased the number of cells expressing apoptotic and proliferative markers. Furthermore, TPF administration significantly reduced the number of cells expressing taste cell markers and the magnitudes of the responses of taste nerves to tastants. The above results suggest that anticancer drug-induced taste dysfunction may be due to a reduction in the number of taste cells expressing taste-related molecules. The suppressive effects of TPF on taste cell marker expression and taste perception were reduced by the drinking of ice-cold water. We speculate that oral cryotherapy with an ice cube might be useful for prophylaxis against anticancer drug-induced taste disorders in humans.

Background: Infection caused by SARS-CoV-2 virus is a recent disease that is easily spread and has serious complications, such as neuropsychiatric signs and symptoms. Thus, studies are necessary on the clinical manifestations during and/or after the course of the disease. Aims and objectives: To describe the relationship between neuropsychiatric signs and symptoms and SARS-CoV-2 infection. Methods: Systematic review conducted in the Pubmed Portal, Brazilian Virtual Health Library, Cochrane, and Science Direct databases. The descriptors coronavirus, SARS, and neurologic symptoms were used in Pubmed, Cochrane, and Science Direct databases, while the descriptors SARS Virus and Nervous System were used in the Virtual Health Library database. A total of 1024 studies were found and 67 were selected to compose this systematic review. The studies were analyzed qualitatively with the narrative description divided into four thematic categories. Results: There is a pathophysiological relationship between SARS-CoV-2 infection and manifestations involving the Central Nervous System and the Peripheral Nervous System through different pathways and mechanisms. The chances of Nervous System manifestations increase in elderly patients with associated morbidities, such as obesity, diabetes mellitus, chronic obstructive pulmonary disease and/or pre-existing neurological/psychiatric diseases. The most cited neuropsychiatric signs and symptoms were headache, delirium, smell and/or taste disorders, and stroke. The evaluation and monitoring of patients during and after COVID-19 infection is important for the early detection and treatment of neuropsychiatric signs and symptoms. Conclusions: It is recommended that health professionals monitor patients with COVID-19 infection or who had recently had the disease for detecting neuropsychiatric signs and symptoms, especially elderly patients, people with comorbidities such as cardiovascular and pulmonary diseases, diabetes mellitus, and obesity, and patients with pre-existing neurological/psychiatric diseases. Decision-making for the implementation of an early rehabilitation treatment can be reinforced in this groups, minimizing the sequels resulting from COVID-19.

Taste dysfunction (TD) has been recognised, together with olfactory dysfunction, as a key presenting symptom of COVID-19. The capability to recognise flavours, flavour intensities and aroma characteristics can be highly variable within the same population, as well as potentially diverse between culturally different populations. The aims of this study are to evaluate whether a difference in the types of TD presentation amongst COVID-19 positive subjects can be demonstrated and whether a difference exists between populations of different cultures.

Background Olfactory and gustatory dysfunction has been reported as characteristic symptoms of coronavirus disease 2019 (COVID-19). This study evaluated olfactory and gustatory dysfunction in mild COVID-19 patients using validated assessment methods. Methods A prospective surveillance study was conducted for mild COVID-19 patients who were isolated at the Gyeonggi International Living and Treatment Support Center (LTSC), Korea. Olfactory function was assessed using the Korean version of the Questionnaire of Olfactory Disorders (QOD) and Cross-Cultural Smell Identification Test (CC-SIT). Gustatory function was assessed using an 11-point Likert scale and 6-n-propylthiouracil, phenylthiocarbamide, and control strips. All patients underwent nasal and oral cavity endoscopic examination. Results Of the 62 patients at the LTSC, 15 patients (24.2%) complained of olfactory or gustatory dysfunction on admission. Four of 10 patients who underwent functional evaluation did not have general symptoms and 2 were asymptomatic. The mean short version of QOD-negative statements and QOD-visual analogue scale scores were 13 ± 6 and 4.7 ± 3.6, respectively. The mean CC-SIT score was 8 ± 2. No patients showed anatomical abnormalities associated with olfactory dysfunction on endoscopic examination. The mean Likert scale score for function was 8 ± 2, and there were no abnormal lesions in the oral cavity of any patient. Conclusions The prevalence of olfactory and gustatory dysfunction was 24.2% in mild COVID-19 patients. All patients had hyposmia due to sensorineural olfactory dysfunction, which was confirmed using validated olfactory and gustatory evaluation methods and endoscopic examination. Olfactory and gustatory dysfunction may be characteristic indicators of mild COVID-19., Graphical Abstract

Introduction: To highlight the importance of the need for new treatment modalities, this study aimed to characterise the experience of patients with postinfectious olfactory dysfunction (PIOD) in terms of the treatment they received. Methods: An online survey was hosted by the Norwich Clinical Trials Unit on the secure REDCap server. Members of the charity Fifth Sense (the UK charity that represents and supports people affected by smell and taste disorders) were invited to participate. Results: There were 149 respondents, of whom 127 had identified themselves as having (or had) PIOD. The age range of respondents to the survey was 28–85 years, with a mean of 58 ± 12 years, with the duration of their disorder Conclusion: There appears to be a need to encourage greater use of guidelines for olfactory disorders amongst medical practitioners and also to develop more effective treatments for patients with PIOD, where there is clearly an unmet need.

There is a relationship between smell and taste disturbances and coronavirus infection. These symptoms have been considered the best predictor of coronavirus infection, for this reason, it was decided to evaluate the predictive value of the smell and taste test and its association with the results of SARS-CoV-2 PCR-RT and rapid diagnostic tests. in the diagnosis of pathology. Methodology: 248 patients divided into 3 groups: asymptomatic, symptomatic without chemosensory disorders, and chemosensory disorders alone. All of them underwent SARS-CoV-2 PCR-RT, a rapid diagnostic test and a test of Venezuelan smell and basic taste at the beginning. Weekly follow-up with smell and taste test and SARS-CoV-2 PCR-RT until recovery. Results: 20.56% of patients had smell and taste disorders to a variable degree and were positive by SARS-CoV-PCR-RT. 2.15.3% of patients with chemosensory disorders were negative for COVID-19. The positive predictive value of the smell and taste test was 57.3; Sensitivity 41.13% and specificity 69.35%. There were no statistically significant differences by age, sex and chemosensory disorders. The predominant chemosensory disorder was the combination of mild hyposmia and hypogeusia and appeared in the company of other symptoms. Recovery occurred in an average of 8.5 days, asynchronously with the SARS-CoV-2 RT-PCR negativization, which occurred up to more than 15 days after the senses recovered. Maximum time of negativization of the RT-PCR of 34 days. Conclusion: chemosensory disorders are a symptom and / or sign of coronavirus disease but cannot be considered as predictors of said disease in this population studied. The gold standard remains the SARS-CoV-2 PCR-RT test. Rapid diagnostic tests should be used for follow-up. Recommendations: it is necessary to expand the sample, include routine psychophysical smell and taste tests to screen cases and take race and virus mutations into consideration to explain behavior in certain populations. Key words: Smell, taste, coronavirus, test, diagnosis.

Objective Loss of smell and taste are considered potential discriminatory symptoms indicating triaging for coronavirus disease 2019 (COVID-19) and early case identification. However, the estimated prevalence essential to guide public health policy varies in published literature. This meta-analysis aimed to estimate prevalence of smell and taste loss among COVID-19 patients. Data Sources We conducted systematic searches of PubMed, Embase, Web of Science, and Google Scholar databases for studies published on the prevalence of smell and taste loss in COVID-19 patients. Review Methods Two authors extracted data on study characteristics and the prevalence of smell and taste loss. Random-effects modeling was used to estimate pooled prevalence. Subgroup analysis and meta-regression were conducted to explore potential heterogeneity sources. This study used PRISMA and MOOSE guidelines. Results Twenty-seven of 32 studies reported a prevalence of loss of smell, taste, or both from a combined sample of 20,451 COVID-19 patients. The estimated global pooled prevalence of loss of smell among 19,424 COVID-19 patients from 27 studies was 48.47% (95% CI, 33.78%-63.29%). Loss of taste was reported in 20 studies and 8001 patients with an estimated pooled prevalence of 41.47% (95% CI, 3.13%-31.03%), while 13 studies that reported combined loss of smell and taste in 5977 COVID-19 patients indicated a pooled prevalence of 35.04% (95% CI, 22.03%-49.26%). Conclusions The prevalence of smell and taste loss among COVID-19 patients was high globally, and regional differences supported the relevance of these symptoms as important markers. Health workers must consider them as suspicion indices for empirical diagnosis of severe acute respiratory syndrome coronavirus 2 infection.

COVID‐19, caused by a novel coronavirus, is a persistent global pandemic. It is crucial to examine existing reports to effectively summarize and characterize its clinical course. We used a large‐scale meta‐analysis to establish prevalence rates for loss of olfaction and gustation in COVID‐19 positive patients. PubMed/Medline, Embase, and Web of Sciences were searched for articles published until April 30, 2020. Furthermore, to avoid missing papers, more searches were carried out in the reference lists of covered studies. Articles that mentioned olfactory and/or gustatory disorder in patients with COVID–19 were included for further analysis. Articles that did not report the aforementioned information were excluded. Duplicated articles, reviews, and meta‐analysis were excluded as well. The quality of the references was assessed according to the checklist provided by JBI (Joanna Briggs Institute). We used independent extraction of data by multiple observers. The pooled frequency with 95% confidence intervals (CI) was assessed using random effect model. The main outcome measures reported were the pooled frequency of olfaction and pooled frequency of gustation disorder in patients with COVID‐19 calculated using a random effect model weighted by the study population. The 15 included studies had 3,739 participants which all had confirmed COVID–19. Olfactory and gustatory disorders were assessed and a total number of 1,354 and 1,729 were reported to have taste or smell impairment, respectively. The estimated rate of taste disorder in patients with COVID‐19 was 49.0% [95% confidence interval (CI) 34.0–64.0, I2: 96%] (Figure 2). The estimated rate of olfactory disorder in patients with COVID‐19 was 61.0% (95% CI 44.0%–75.0%). Our meta‐analysis demonstrated high rates of taste (49.0%) and smell (61.0%) disorders in patients with confirmed COVID‐19. Results increase the power of recent reports—loss of olfactory and loss of gustation should now routinely be considered in the setting of COVID‐19 infection., Impaired olfaction and gustation should be used to aid in the early diagnosis and effective viral containment of COVID‐19. The estimated prevalence rate of taste disorder was 49%in patients with confirmed COVID‐19. The estimated prevalence rate of smell disorder was 61%in patients with confirmed COVID‐19.

Smell and taste disorders occur in COVID-19 with a high prevalence, but little is known about the duration of the symptoms. In particular, studies using validated olfactory tests are very rare to date.The aim of this study was to determine the olfactory function of COVID-19 recoveries by a detailed olfactory test.91 patients with PCR-confirmed, past COVID-19 disease were included. Olfactory history was taken using a questionnaire. Olfactory function was evaluated with the sniffin' sticks test, tasting function with taste sprays.80 patients had experienced sudden olfactory loss during the course of disease and at the time of testing, 33 patients subjectively still had an impaired olfactory sense. Around 8 weeks had passed since the onset of symptoms. 45.1% of the tested individuals were still hyposmic according to the olfactory test while 53.8% showed an olfactory performance within the normal range. Patients' self-assessment correlated poorly with the measured olfactory performance.Half of the patients with an olfactory loss as a symptom of COVID-19 still have olfactory impairments after two months, although not all of these patients subjectively notice a restriction. Long-term measurements must confirm whether all affected patients will make full recovery.

BackgroundThe novel Coronavirus Disease-19 (COVID-19) continues to have profound effect on global health. Our aim was to evaluate the prevalence and characterize specific symptoms associated with COVID-19.MethodsThis retrospective study included 326 patients with confirmed SARS-CoV-2 infection evaluated at the Emergency Department of the Umberto I Polyclinic Hospital, Rome, Italy between March 6th and April 30th, 2020. In order to assess xerostomia, olfactory and gustatory dysfunctions secondary to COVID-19, a telephone-based a modified survey obtained from the National Health and Nutrition Examination Survey (NHANES) 2013-2014 for taste and smell disorders and the Fox Questionnaire for dry mouth were administered to 111 patients (34%) after discharge between June 4th and June 12th.ResultsTaste dysfunction was the most common reported symptom (59.5%; n=66), followed by xerostomia (45.9%; n=51) and olfactory dysfunctions (41.4%; n=46). The most severe symptom was olfactory dysfunction with a median severity score of 8.5 (range: 5-10). Overall 74.5% (n=38) of patients with xerostomia, 78.8% (n=52) of patients with gustatory dysfunctions and 71.1% (n=33) of patients with olfactory dysfunctions reported that all symptoms appeared before COVID-19 diagnosis. Overall, the majority of patients reported one symptom only (45.9%, n=51), 37 (33.3%) reported the association of two symptoms, and 23 (20.7%) patients reported the association of three symptoms at the same time.ConclusionXerostomia, gustatory and olfactory dysfunctions may present as a prodromal or as the sole manifestation of COVID-19. Awareness is fundamental to identify COVID-19 patients at an early stage of the disease and limit the spread of the virus.

The 2019 novel coronavirus disease (COVID-19) pandemic poses unique challenges to the medical community as the optimal treatment has not been determined and is often at the discretion of institutional guidelines. Pregnancy has previously been described as a high-risk state in the context of infectious diseases, given a particular susceptibility to pathogens and adverse outcomes. Although ongoing studies have provided insight on the course of this disease in the adult population, the implications of COVID-19 on pregnancy remains an understudied area. The objective of this study is to review the literature and describe clinical presentations among pregnant women afflicted with COVID-19.

Background The lack of objective data makes it difficult to establish the prognostic value of chemosensitive disorders in coronavirus disease 2019 (COVID-19) patients. We aimed to prospectively monitor patients diagnosed with COVID-19 to see if the severity of olfactory and gustatory dysfunction associates with subsequent disease severity. Methods Multicentre prospective study that recruited 106 COVID-19 subjects at diagnosis. Chemosensitive functions were assessed with psychophysical tests within 4 days of clinical onset, at 10 and 20 days. Daily body temperature and oxygen saturation were recorded as markers of disease severity alongside need for hospitalisation. The correlation between olfactory and gustatory scores and disease severity was assessed with linear regression analysis. Results At T0, 71 patients (67%) presented with olfactory dysfunction while gustatory impairment was detected in 76 cases (65.6%). Chemosensitive disorders gradually improved over the observation period. No significant correlations were found between T0 chemosensitive scores and final disease severity. The correlation between olfactory scores and fever proved significant at T2 (p = 0.05), while the relationship with gustatory scores was significant at T1 (p = 0.01) and T2 (p p p = 0.005). Conclusions Initial objective olfactory and gustatory scores do not seem to have a significant prognostic value in predicting the severity of the COVID-19 course; however, persistence of olfactory dysfunction at 20 days, associated with a more severe course. Unfortunately, olfactory and gustatory dysfunction do not seem to hold prognostic value at the time of initial diagnosis.

Purpose of Review Olfactory dysfunction in upper airway viral infections (common cold, acute rhinosinusitis) is common (> 60%). During the COVID-19 outbreak, frequency of sensory disorders (smell and/or taste) in affected patients has shown a high variability from 5 to 98%, depending on the methodology, country, and study. Recent Findings A sudden, severe, isolated loss of smell and/or taste, in the absence of other upper airway inflammatory diseases (allergic rhinitis, chronic rhinosinusitis, nasal polyposis), should alert individuals and physicians on being potentially affected by COVID-19. The evaluation of smell/taste disorders with a visual analogue scale or an individual olfactory or gustatory test, at the hospital or by telemedicine, to prevent contamination might facilitate an early detection of infected patients and reduce the transmission of SARS-CoV-2. Summary During the COVID-19 outbreak, patients with sudden loss of smell should initiate social distancing and home isolation measures and be tested for SARS-CoV-2 diagnostic test when available. Olfactory training is recommended when smell does not come back after 1 month but can be started earlier.

Over the course of the pandemic due to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), multiple new clinical manifestations, as the consequence of the tropism of the virus, have been recognized. That includes now the neurological manifestations and conditions, such as headache, encephalitis, as well as olfactory and taste disorders. We present a series of ten cases of RT-PCR-confirmed SARS-CoV-2-infected patients diagnosed with viral-associated olfactory and taste loss from four different countries.

Background An intact sense of taste provides pleasure, supports sustenance and alerts the body to toxins. Head and neck cancer (HNC) patients who receive radiotherapy (RT) are high-risk for developing radiation-induced taste dysfunction. Advances in RT offer opportunities for taste-preserving strategies by reducing dose to the gustatory organs-at-risk. Methods PubMed, Medline and EMBASE were searched for publications reporting on taste, RT and HNC. Randomised trials, cohort studies and cross-sectional studies were included. Results 31 studies were included in this review. Meta-analysed prevalence of acute taste dysfunction following RT was approximately 96% (95% CI 64 to 100%) by objective measures and 79% (95% CI 65 to 88%) by subjective measures, with the majority of patients showing at least partial recovery. Long-term dysfunction was seen in ~25% of patients. Taste dysfunction was associated with sequalae including weight loss and reduced quality-of-life (QoL). Taste dysfunction was more common when the oral cavity, and specifically the anterior two-thirds of the tongue, was irradiated, suggesting a dose constraint for taste preservation might be feasible. Proton beam therapy and customised bite blocks reduced dose to the gustatory field and subsequent loss of taste. Conclusions Taste dysfunction following RT is common and negatively affects patients’ nutritional status and QoL. Decisions about treatment strategies, including choice of RT modality, dose distribution across the gustatory field and the use of adjuncts like bite blocks may be beneficial. However, evidence is limited. There is a pressing need for randomised studies or large prospective cohort studies with sufficient adjustment for confounders.

We thank our colleagues for their constructive discussion on our recently published study1. Regarding prevalence, indeed, growing literature yields a variable frequency of loss of smell (LOS) in Covid‐19 patients, that may be hypothetically due to differences in the location and amount of viral load, to the different immune response between younger mild‐symptomatic outpatients (higher prevalence) and more severely affected inpatients (lower prevalence)1,2, and to the variable methods of measurement.

BackgroundRapid spread of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and concern for viral transmission by ambulatory patients with minimal to no symptoms underline the importance of identifying early or subclinical symptoms of coronavirus disease 2019 (COVID-19) infection. Two such candidate symptoms include anecdotally reported loss of smell and taste. Understanding the timing and association of smell/taste loss in COVID-19 may help facilitate screening and early isolation of cases.MethodsA single-institution, cross-sectional study evaluating patient-reported symptoms with a focus on smell and taste was conducted using an internet-based platform on adult subjects who underwent testing for COVID-19. Logistic regression was employed to identify symptoms associated with COVID-19 positivity.ResultsA total of 1480 patients with influenza-like symptoms underwent COVID-19 testing between March 3, 2020, and March 29, 2020. Our study captured 59 of 102 (58%) COVID-19-positive patients and 203 of 1378 (15%) COVID-19-negative patients. Smell and taste loss were reported in 68% (40/59) and 71% (42/59) of COVID-19-positive subjects, respectively, compared to 16% (33/203) and 17% (35/203) of COVID-19-negative patients (p < 0.001). Smell and taste impairment were independently and strongly associated with COVID-19 positivity (anosmia: adjusted odds ratio [aOR] 10.9; 95% CI, 5.08-23.5; ageusia: aOR 10.2; 95% CI, 4.74-22.1), whereas sore throat was associated with COVID-19 negativity (aOR 0.23; 95% CI, 0.11-0.50). Of patients who reported COVID-19-associated loss of smell, 74% (28/38) reported resolution of anosmia with clinical resolution of illness.ConclusionIn ambulatory individuals with influenza-like symptoms, chemosensory dysfunction was strongly associated with COVID-19 infection and should be considered when screening symptoms. Most will recover chemosensory function within weeks, paralleling resolution of other disease-related symptoms.

OBJECTIVE To evaluate the incidence of certain symptoms in a population of health workers exposed to coronavirus disease 2019 patients. STUDY DESIGN Case-control study. METHODS The study was conducted at a tertiary care hospital from March 1 to April 7, 2020. Health workers with suspected coronavirus disease 2019 (COVID-19) infection were included. The presence of COVID-19 was detected by using real-time polymerase chain reaction (RT-PCR) methods. Positive and negative RT-PCR patients were used as case and control groups, respectively. This study analyzed the incidence of COVID-19 symptoms in both patient groups. Visual analog scales were used for self-assessment of smell and taste disorders, ranging from 0 (no perception) to 10 (excellent perception). RESULTS There were 215 (60.6%) patients with positive RT-PCR and 140 (39.4%) patients with negative RT-PCR. The presence of symptoms such as hyposmia hypogeusia, dysthermia, and cough were strongly associated with a positive RT-PCR. The association of cough and subjective hyposmia had 5.46 times higher odds of having a positive test. The receiver operating characteristic (ROC) analysis showed that a fever higher than 37.45°C resulted in sensitivity and specificity of 0.65 and 0.61, respectively. A total of 138 cases (64.1%) and 114 cases (53%) had subjective hyposmia and hypogeusia, respectively. The 85.4% of these patients recovered olfactory function within the first 14 days of the onset of the symptoms. CONCLUSION There is a significant association between positive RT-PCR and subjective hyposmia. The association of subjective hyposmia and cough increase significantly the odds of having a positive RT-PCR. The measurement of fever as the only method for screening of COVID-19 infection resulted in a poor association. LEVEL OF EVIDENCE 3 Laryngoscope, 130:2674-2679, 2020.

IntroductionBackground and rationaleSmell is the forgotten sense; even when facing a problem with their sense of smell, patients often struggle to get recognition, let alone diagnosis or treatment from healthcare professionals. Olfactory disorders are as common as profound hearing loss and blindness affecting an estimated 5% of the population1. Common causes of olfactory disorders include chronic rhinosinusitis, post-viral olfactory loss and post-traumatic olfactory loss2 as well as it being present in the majority of cases of Parkinson’s disease and common in Alzheimer’s disease. We are now also witnessing the rise of sudden onset anosmia as a marker of Covid-19 coronavirus infection3-9. It remains to be seen how many new cases of lasting olfactory loss will arise from those afflicted by the pandemic.Recent population studies have now identified anosmia as an independent risk factor for shortened longevity, even after controlling for dementia and cardiovascular disease10-13. It is not clear why this is so but may suggest that the olfactory system acts as a barometer of environmental impact on the central nervous system as a whole. As this phenomenon has been observed in several countries it clearly demonstrates that olfactory disorders deserve to receive greater attention than they currently do.Taste is often thought to be lost by those affected by olfactory disorders due to the misperception of retronasal olfaction as a “taste” sensation. In reality only a small percentage of people reporting a problem with their sense of smell or taste experience a true gustatory disorder, but due to this common misperception alongside the need to be representative of all patients with chemosensory disorders, it is always important to encapsulate both senses within any work of this kind.Fifth Sense, the UK charity for people affected by smell and taste disorders, was founded in 2012 when authors DB and CP met and agreed on the need for patient advocacy to tackle the unmet needs of patients affected by olfactory disorders. Since then, with the help of a growing membership, we have been able to characterise the significant impact of olfactory disorders on those affected14,15 and we have also become aware of the frustrations many members in their dealings with the medical profession and getting their sensory loss taken seriously15-17. In 2019, Fifth Sense was awarded a National Lottery Grant for £238,815 to enable it to develop and grow its work, including the establishment of a network of patient support hubs.ObjectivesFollowing on from the above, this study aimed to characterise the details of the difficulties faced by patients with olfactory disorders in accessing healthcare as a patient and public co-production18. This will help us jointly address these issues through the work of the National Lottery Grant in 2020-2023.

Background: Anosmia and ageusia are acknowledged as pathognomonic symptoms for SARS-CoV-2 infection by now. Smell-and taste disorders were significantly more frequent in COVID- 19 patients than in influenza patients. Disease characteristics show an acute onset and an initial manifestation of anosmia and ageusia. These symptoms have been linked to a neuroinvasive course of disease. Methods: In this study we investigated five consecutive COVID-19 patients with a prolonged course of anosmia and ageusia by conducting a Burghart Screening 12 Test with taste stripes in the late stage of the disease. Those with objectifiable alteration in taste or smell were subjected to MRI with contrast agent to investigate possible involvement of the central nervous system. Results: We found anosmia and ageusia to be mostly objectifiable, but no evidence for neuroinvasiveness could be detected by MRI in the late stage of the disease. Conclusions: Alterations in taste and smell could be objectified in most patients. Nevertheless, no evidence for a neuroinvasive potential could be identified by MRI, at least in the late stage of disease. We encourage medical professionals to conduct specialised examinations and MRIs in the acute stage of disease, which guarantees an optimum patient care.

From the first reports, ageusia and anosmia appear to be frequent clinical features in coronavirus disease 19 (COVID-19) patients. We have performed a survey of the literature, analyzing the possible causes of these chemosensory alterations, which may be useful as a starting point for specific further studies. This article is protected by copyright. All rights reserved.

Early reports of SARS-CoV-2 infections only rarely mentioned smell and taste disorders. Several studies, particularly from Europe and the USA, have now confirmed these symptoms as an early key feature of COVID-19. About 70 % of patients seem to experience a reduction of smell and taste in the course of the disease, with most of the studies published to date based on questionnaires and anamnestic data. Validated smell tests have so far only been used in a few studies. A distinction between taste and taste disorders, i. e. a distinction between retronasal aroma taste and the olfactory system from the dysfunction of taste capsules and the further cranial nerves, was mostly not made in the studies available to date. Some reports associate olfactory disorders with a milder clinical course. At the same time, the olfactory system via the olfactory bulb represents an entry point into the central nervous system, and an olfactory disorder could be a predisposing factor for central neurological symptoms. The clinical significance of smell and taste disorders in COVID-19 patients is currently still unclear. Further open questions concern the exact prevalence and the prognosis, so that overall higher quality studies with validated smell tests and larger numbers of patients are required.Nachdem anfängliche Berichte über die SARS-CoV-2-Infektion Riech- und Schmeckstörungen kaum erwähnten, haben mittlerweile mehrere Studien, insbesondere aus Europa und den USA, diese Symptome als Merkmal von COVID-19 bestätigt. Gut 2 Drittel der Erkrankten scheinen im Verlauf der Erkrankung eine Riech- und Schmeckminderung zu erleiden, wobei die meisten der bislang veröffentlichten Studien auf Fragebögen und anamnestischen Daten basieren. Validierte Riechtests wurden bislang nur in wenigen Studien eingesetzt. Eine Unterscheidung zwischen Schmeck- und Geschmacksstörungen, also eine Abgrenzung des retronasalen Aromaschmeckens über das olfaktorische System von der Dysfunktion von Geschmackspapillen und der weiterführenden Hirnnerven, erfolgte in den bisher verfügbaren Studien zumeist nicht. Einige Berichte assoziieren die Riechstörungen mit einem milderen klinischen Krankheitsverlauf. Gleichzeitig stellt das Riechsystem über den Bulbus olfactorius eine Eintrittspforte in das zentrale Nervensystem dar, und eine Riechstörung könnte ein prädisponierender Faktor für zentral-neurologische Symptome sein. Die klinische Bedeutung von Riech- und Schmeckstörungen bei COVID-19-Patienten ist aktuell noch unklar. Weitere offene Fragen betreffen die genaue Prävalenz und die Prognose, sodass insgesamt höherwertige Studien mit validierten Riechtests und größeren Patientenzahlen zu fordern sind.

ZusammenfassungNachdem anfängliche Berichte über die SARS-CoV-2-Infektion Riech- und Schmeckstörungen kaum erwähnten, haben mittlerweile mehrere Studien, insbesondere aus Europa und den USA, diese Symptome als Merkmal von COVID-19 bestätigt. Gut 2 Drittel der Erkrankten scheinen im Verlauf der Erkrankung eine Riech- und Schmeckminderung zu erleiden, wobei die meisten der bislang veröffentlichten Studien auf Fragebögen und anamnestischen Daten basieren. Validierte Riechtests wurden bislang nur in wenigen Studien eingesetzt. Eine Unterscheidung zwischen Schmeck- und Geschmacksstörungen, also eine Abgrenzung des retronasalen Aromaschmeckens über das olfaktorische System von der Dysfunktion von Geschmackspapillen und der weiterführenden Hirnnerven, erfolgte in den bisher verfügbaren Studien zumeist nicht. Einige Berichte assoziieren die Riechstörungen mit einem milderen klinischen Krankheitsverlauf. Gleichzeitig stellt das Riechsystem über den Bulbus olfactorius eine Eintrittspforte in das zentrale Nervensystem dar, und eine Riechstörung könnte ein prädisponierender Faktor für zentral-neurologische Symptome sein. Die klinische Bedeutung von Riech- und Schmeckstörungen bei COVID-19-Patienten ist aktuell noch unklar. Weitere offene Fragen betreffen die genaue Prävalenz und die Prognose, sodass insgesamt höherwertige Studien mit validierten Riechtests und größeren Patientenzahlen zu fordern sind.

INTRODUCTION: The coronavirus disease 2019 (COVID 19) is a communicable disease caused by a novel coronavirus. OBJECTIVES: This study aimed to assess self­reported frequency of gastrointestinal symptoms and olfactory or taste disorders in nonhospitalized patients with COVID­19 in Poland. PATIENTS AND METHODS: This cross­sectional survey was conducted between April 17 and 18, 2020, in 4516 nonhospitalized patients with COVID­19 in Poland. The questionnaire included 8 questions related to the health status, symptoms of COVID­19, comorbidities, and smoking status. RESULTS: Completed questionnaires were obtained from 1942 patients with COVID­19 with a response rate of 43%. The median age of the respondents was 50 years; 60.2% were women. Among nonhospitalized patients with COVID­19, 21.3% had hypertension, 4.5% had diabetes, and 3.1% had a chronic respiratory disease. Regular tobacco use was declared by 11.2% of patients with COVID­19. At least one gastrointestinal symptom was reported by 53.6% of patients. Almost half of patients (47%) with COVID­19 reported lack of appetite and 24.2% reported diarrhea. Among 1942 interviewed patients, 54.2% reported at least 1 olfactory or taste disorder and 42.5% reported both alterations. Self­reported olfactory and taste disorders were 49.2% and 47.5%, respectively. Self­reported frequency of gastrointestinal symptoms and olfactory or taste disorders during COVID­19 was significantly higher (P

Objectiveto quantitatively assess disturbances of sweet, sour and salty and bitter tastes in a group of young, asymptomatic or oligosymptomatic COVID-19 patients; establish a reliable, sensitive and specific test that can diagnose COVID-19 on the basis of taste disorders and publish the results according to STARD 2015 statement (Standards for Reporting Diagnostic Accuracy).Designcase-control studySettingisolated rooms in the Central Clinical Hospital of the Ministry of the Interior and Administration in Warsaw (which had been transformed into an infectious hospital) and a dormitory in one of Warsaw universities.Participants52 SARS-CoV-2 positive (51 men, mean age 21.7 years) and 36 negative students (34 men, mean age 20.8 years).Main outcome measuresa gustatory function assessment (sweet, salty, sour and bitter taste), with flavour concentrations established previously in healthy subjects was conducted for all subjects. Each participant received one tasteless reference and nine flavour tablets with sucrose concentrations of 40, 80 and 106.4 mg/ml; NaCl at 13.5, 17 and 27 mg/ml; ascorbic acid at 6.25 and 12.5 mg/ml and grapefruit extract at 40 mg/ml.Resultsthe only taste that was impaired significantly more frequently in COVID-19 patients was the sweet taste at the lowest flavour concentration (40 mg/ml, p = 0.002). Different screening and diagnostic models were constructed using the examined variables. The highest accuracy screening test consisted of the positive result of a three-question questionnaire (self-reported loss of taste, self-reported loss of smell, or fever within the last month (positive if at least one present) and/or ageusia of sweet taste at a sucrose concentration of 40 mg/ml. The sensitivity of the model was 94% with a specificity of 55%. The highest accuracy diagnostic test consisted of ageusia of sweet taste at a sucrose concentration of 106.4 mg/ml or/and ageusia of salty taste at an NaCl concentration of 13.5 or 17 mg/ml. The specificity of the test was found to be 100%, and the sensitivity was 34%.Conclusionas the most effective way of controlling the present pandemic involves testing the wider population for symptomatic, oligosymptomatic and asymptomatic carriers of SARSCoV-2 and isolating or hospitalising infected subjects, in the present study, an inexpensive, simple, fast and sensitive (94%) screening test that can be used for such a purpose is proposed. In addition, a specific (100%) diagnostic test that could be used to refer patients to quarantine in the case of limited availability of genetic or serological tests is proposed.

Objective To estimate the prevalence of olfactory and gustatory dysfunctions (OGDs) among patients infected with novel coronavirus disease 2019 (COVID-19). Patients and Methods A systematic review was conducted by searching MEDLINE, EMBASE, and the preprint server MedRxiv until 11 May 2020 using the terms ‘anosmia’ or ‘hyposmia’ or ‘dysosmia’ or ‘olfactory dysfunction’ or ‘olfaction disorder’ or ‘smell dysfunction’ or ‘ageusia’ or ‘hypogeusia’ or ‘dysgeusia’ or ‘taste dysfunction’ or ‘gustatory dysfunction’ or ‘neurological’ and ‘COVID-19’ or ‘2019 novel coronavirus’ or ‘2019-nCoV’ or ‘SARS-CoV-2’. References of included studies were also manually screened. Only studies involving diagnostic-confirmed patients with COVID-19 were included. Random-effects meta-analysis was performed. Results A total of twenty-four studies with data from 8438 test-confirmed COVID-19 patients from thirteen countries were included. The pooled proportion of patients presenting with olfactory and gustatory dysfunctions was 41.0% (95% confidence interval [CI] 28.5% to 53.9) and 38.2% (95% CI 24.0 to 53.6%), respectively. Increasing mean age correlated with lower prevalence of olfactory (coefficient = -0.076; p=.02) and gustatory (coefficient = -0.073; p=.03) dysfunctions. There was a higher prevalence of olfactory dysfunctions with the use of objective measurements compared to self-reports (coefficient = 2.33; p=.01). No significant moderation of the prevalence of OGDs by gender was observed. Conclusion There is a high prevalence of OGDs among patients infected with COVID-19. Routine screening for these conditions could contribute to improved case detection in the ongoing COVID-19 pandemic. However, to better inform population screening measures, further studies are needed to establish causality.

Purpose To estimate the prevalence of smell or taste impairment in household contacts of mildly symptomatic home-isolated SARS-CoV-2 positive patients.Methods Cross sectional study based on ad hoc questions.Results Of 214 mildly symptomatic COVID-19 patients managed at home under self-isolation, 179 reported to have at least one household contact, with the total number of no study participants contacts being 296. Among 175 household contacts not tested for SARS-CoV-2 infection, 67 (38.3%) had SARS-CoV-2 compatible symptoms, 39 (22.3%) had loss of smell or taste with 7 (4.0%) having loss of smell or taste in the absence of other symptoms. The prevalence of smell or taste impairment was 1.5% in patients tested negative compared to 63.0% of those tested positive for SARS-CoV-2 (pConclusion Smell or taste impairment are quite common in not-tested household contacts of mildly symptomatic home-isolated SARS-CoV-2 positive patients. This should be taken into account when estimating the burden of loss of sense of smell and taste during COVID-19 pandemic, and further highlights the value of loss of sense of smell and taste as a marker of infection.

Background For patients with breast cancer treated with certain chemotherapy regimens, taste disorders associated with those regimens can negatively affect quality of life. Objectives This study evaluated the effects of taste disorder-related education on meal satisfaction and sense of taste in Japanese women with breast cancer undergoing chemotherapy. Methods A sample of 53 newly diagnosed women with breast cancer scheduled for chemotherapy treatment were randomly assigned to the control or intervention (nurse-provided education about chemotherapy-associated taste disorders) group. Meal satisfaction and sense of taste were assessed using a visual analog scale. Findings The proportions of patients with meal dissatisfaction and impaired sense of taste were lower in the intervention group than in the control group. Although meal dissatisfaction and impaired sense of taste recovered in the intervention group two months after protocol completion, they did not recover in the control group. Providing education to women with breast cancer scheduled for chemotherapy treatment can affect patients' experience of treatment-associated taste disorders.

Olfactory and Taste Disorders and COVID-19: Our experience in 77 adults in the North East of England.

Objective We aim to summarize reliable evidence of evidence‐based medicine for the treatment and prevention of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) by analyzing all the published studies on the clinical characteristics of patients with SARS‐CoV‐2. Methods PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of SARS‐CoV‐2 infection were collected for meta‐analysis. Results Ten studies were included in Meta‐analysis, including a total number of 50466 patients with SARS‐CoV‐2 infection. Meta‐analysis shows that, among these patients, the incidence of fever was 0.891 (95% CI: 0.818, 0.945), the incidence of cough was 0.722 (95% CI: 0.657, 0.782), and the incidence of muscle soreness or fatigue was 0.425 (95% CI: 0.213, 0.652). The incidence of acute respiratory distress syndrome (ARDS) was 0.148 (95% CI: 0.046, 0.296), the incidence of abnormal chest computer tomography (CT) was 0.966 (95% CI: 0.921, 0.993), the percentage of severe cases in all infected cases was 0.181 (95% CI: 0.127, 0.243), and the case fatality rate of patients with SARS‐CoV‐2 infection was 0.043 (95% CI: 0.027, 0.061). Conclusion Fever and cough are the most common symptoms in patients with SARS‐CoV‐2 infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms are rare. The case fatality rate of patients with SARS‐CoV‐2 infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). This meta‐analysis also has limitations, so the conclusions of this Meta‐analysis still need to be verified by more relevant studies with more careful design, more rigorous execution, and larger sample size., Highlights A total of 10 articles were included in the Meta‐analysis, including 50466 patients with SARS‐CoV‐2 infection, which was by far the first Meta‐analysis with the largest sample size. The quality of the literature included in this study is high, the analysis performed is rigorous, and the conclusions drawn by this study are highly credible.

Olfactory and taste dysfunctions have emerged as symptoms of COVID-19. Among individuals with COVID-19 enrolled in a household study, loss of taste and/or smell was the fourth most commonly reported symptom (26/42; 62%), and among household contacts, it had the highest positive predictive value (83%; 95% CI: 55-95%) for COVID-19. These findings support consideration of loss of taste and/or smell in possible case identification and testing prioritization for COVID-19.

HIGHLIGHTS • Isolated loss of smell without nasal obstruction is an early red-flag of COVID-19 • These patients should adopt all the preventive measures and a lockdown • Olfactory/gustative dysfunction had high predictive value to identify COVID-19 • Olfactory/gustative dysfunction had high specificity to identify COVID-19 • Self-reported loss of smell, among other symptoms, could help to screen COVID-19, Objectives To determine the frequency of SARS-CoV-2 positive samples in a subset of patients consulting for primarily isolated acute (

Background: This systematic review had three aims: i) to determine the frequency of anosmia (or other smell disorders) and dysgeusia (or other taste disorders) in COVID-19 patients; ii) to determine whether anosmia or dysgeusia are independently associated with COVID-19 diagnosis; and iii) to determine whether anosmia or dysgeusia are prognostic factors for impaired outcomes among COVID-19 patients. Methods: On April 20th, 2020, we search MEDLINE, Embase, Global Health, Scopus, Web of Science and MedXriv. We used terms related to COVID-19, smell and taste disorders. We selected case series, cross-sectional, case-control and cohort studies. We included studies with COVID-19 patients describing their symptoms; studies that compared smell and taste disorders between COVID-19 patients and otherwise healthy subjects; and studies comparing smell and taste disorders between COVID-19 severe and mild/moderate cases. Because of methodological heterogeneity and the limited number of results, a qualitative synthesis is presented. Results: From 31 reports, we selected six (n=2,757). Six studies reported the proportion of smell and taste disorders among COVID-19 patients. Two reports studied whether smell and taste disorders were independently associated with COVID-19 diagnosis. No reports studied the association with impaired outcomes among COVID-19 patients. The frequency of anosmia ranged between 22%-68%. The definition of taste disorders varied greatly, with dysgeusia present in 33% and ageusia in 20%. People who reported loss of smell and taste had six-fold higher odds of being COVID-19 positive; similarly, anosmia and ageusia were associated with 10-fold higher odds of COVID-19 diagnosis. Conclusions: The frequency of smell and taste disorders is as high as other symptoms, thus, at least anosmia for which the definition was more consistent, could be included in lists of COVID-19 symptoms. Although there is promising evidence, it is premature to conclude that smell and taste disorders are strongly associated with COVID-19 diagnosis. Registration: PROSPERO CRD42020181308

Objective: Review and integrate the neurologic manifestations of the Coronavirus Disease 2019 (COVID-19) pandemic, to aid medical practitioners who are combating the newly derived infectious disease. Methods: We reviewed the clinical research, consisting of mainly case series, on reported neurologic manifestations of COVID-19. We also reviewed basic studies to understand the mechanism of these neurologic symptoms and signs. Results: We included 79 studies for qualitative synthesis and 63 studies for meta-analysis. The reported neurologic manifestations were olfactory/taste disorders (35.6%), myalgia (18.5%), headache (10.7%), acute cerebral vascular disease (8.1%), dizziness (7.9%), altered mental status (7.8%), seizure (1.5%), encephalitis, neuralgia, ataxia, Guillain-Barre syndrome, Miller Fisher syndrome, intracerebral hemorrhage, polyneuritis cranialis, and dystonic posture. Conclusions: Neurologic manifestations in COVID-19 may alert physicians and medical practitioners to rule in high-risk patients. The increasing incidence of olfactory/taste disorders, myalgia, headache, and acute cerebral vascular disease renders a possibility that COVID-19 could attack the nervous system. The cytokine secretion and bloodstream circulation (viremia) are among the most possible routes into the nervous system.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly worldwide. Given scarce resources, nonlaboratory diagnostics are crucial. In this cross-sectional study, two-thirds of European patients with confirmed COVID-19 reported olfactory and gustatory dysfunction, indicating the significance of these symptoms in early diagnostics.

BACKGROUND AND PURPOSE: Specific respiratory tract infections, including COVID-19, may cause smell and/or taste disorders (STDs) with increased frequency. The aim was to determine whether new-onset STDs are more frequent amongst COVID-19 patients than influenza patients. METHOD: This was a case-control study including hospitalized patients of two tertiary care centres. Consecutive patients positive for COVID-19 polymerase chain reaction (cases) and patients positive for influenza polymerase chain reaction (historical control sample) were assessed during specific periods, employing a self-reported STD questionnaire. RESULTS: Seventy-nine cases and 40 controls were included. No significant differences were found in basal features between the two groups. New-onset STDs were significantly more frequent amongst cases (31, 39.2%) than in the control group (5, 12.5 %) [adjusted odds ratio 21.4 (2.77-165.4, P = 0.003)]. COVID-19 patients with new-onset STDs were significantly younger than COVID-19 patients without STDs (52.6 ± 17.2 vs. 67.4 ± 15.1, P

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