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To estimate the prevalence of olfactory and gustatory dysfunctions (OGDs) among patients infected with novel coronavirus disease 2019 (COVID-19). A systematic review was conducted by searching MEDLINE, EMBASE, and the preprint server MedRxiv from their inception until May 11, 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. The references of included studies were also manually screened. Only studies involving patients with diagnostic-confirmed COVID-19 infection were included. Random-effects meta-analysis was performed. Twenty-four studies with data from 8438 patients with test-confirmed COVID-19 infection from 13 countries were included. The pooled proportions of patients presenting with olfactory dysfunction and gustatory dysfunction were 41.0% (95% 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 with self-reports (coefficient = 2.33; P=.01). No significant moderation of the prevalence of OGDs by sex was observed. 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.

Despite signs of infection—including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules—the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission. Single-cell transcriptomics and protein expression analyses of salivary glands and gingiva, along with the detection of infectious virus and virus-specific antibodies in saliva from SARS-CoV-2-infected individuals, support a potential role for the oral cavity in COVID-19 pathogenesis.

The long-term recovery rate of chemosensitive functions in coronavirus disease 2019 patients has not yet been determined. A multicentre prospective study on 138 coronavirus disease 2019 patients was conducted. Olfactory and gustatory functions were prospectively evaluated for 60 days. Within the first 4 days of coronavirus disease 2019, 84.8 per cent of patients had chemosensitive dysfunction that gradually improved over the observation period. The most significant increase in chemosensitive scores occurred in the first 10 days for taste and between 10 and 20 days for smell. At the end of the observation period (60 days after symptom onset), 7.2 per cent of the patients still had severe dysfunctions. The risk of developing a long-lasting disorder becomes significant at 10 days for taste (odds ratio = 40.2, 95 per cent confidence interval = 2.204-733.2, p = 0.013) and 20 days for smell (odds ratio = 58.5, 95 per cent confidence interval = 3.278-1043.5, p = 0.005). Chemosensitive disturbances persisted in 7.2 per cent of patients 60 days after clinical onset. Specific therapies should be initiated in patients with severe olfactory and gustatory disturbances 20 days after disease onset.

IntroductionNeurological manifestations can occur during coronavirus disease 19 (COVID-19). Several pathogenic mechanisms have been hypothesized, without conclusive results. In this study, we evaluated the most frequent neurological symptoms in a cohort of hospitalized COVID-19 patients, and also investigated the possible relationship between plasmatic inflammatory indices and olfactory disorders (ODs) and between muscle pain and creatine kinase (CK).MethodsWe consecutively enrolled hospitalized COVID-19 patients. A structured questionnaire concerning typical and neurological symptoms, focusing on headache, dizziness, ODs, taste disorders (TDs), and muscle pain, was administrated by telephone interviews.ResultsCommon neurological symptoms were reported in the early phase of the disease, with a median onset ranging from 1 to 3 days. Headache showed tension-type features and was more frequently associated with a history of headache. Patients with ODs less frequently needed oxygen therapy. Inflammatory indices did not significantly differ between patients with and without ODs. Muscle pain did not show any association with CK level but was more frequently associated with arthralgia and headache.ConclusionIn our cohort, ODs were an early symptom of COVID-19, more frequently reported by patients with milder forms of disease. Headache in association with arthralgia and muscle pain seems to reflect the common symptoms of the flu-like syndrome, and not COVID-19 infection-specific.

Purpose of ReviewOlfactory 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 FindingsA 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.SummaryDuring 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.

Olfactory and gustatory dysfunctions (OGD) are pathognomonic symptoms in patients with Coronavirus Disease 2019 (COVID-19). This study reviews the associations of OGD with COVID-19 which will be useful for early diagnosis and self-isolation. Systematic searches of PubMed, Ovid Medline, Scopus, and EMBASE electronic databases were performed. Studies reporting OGD in COVID-19 patients were included. Data were pooled for meta-analysis. The outcomes were odds ratios (OR) of OGD in COVID-19 patients. Proportions of smell and/or taste dysfunctions in the COVID-19 patients were assessed. Fourteen studies (21,515 participants, age 49.12 years, 26% male) were included. The OR of olfactory and/or gustatory dysfunctions in COVID-19 patients were 11.26 (95% confidence interval (CI) 5.41 to 23.4) when compared with acute respiratory infection (ARI) without detectable virus and 6.46 (95% CI 2.79 to 14.97) in patients with other respiratory viruses. The OR of olfactory dysfunction in COVID-19 patients were 11.67 (95% CI 6.43 to 21.17) when compared with the ARI patients without detectable virus and 4.17 (95% CI 1.34 to 12.98) with other respiratory viruses. The OR of gustatory dysfunction in COVID-19 patients were 12.70 (95% CI 7.9 to 20.44) when compared with the ARI patients without detectable virus and 4.94 (95%CI 1.59 to 15.31) with other respiratory viruses. Fifty percent (95% CI 36.7 to 63.3%) of COVID-19 patients had olfactory and/or gustatory dysfunctions. In summary, there are associations between OGD and COVID-19 patients. Patients presenting with ARI should be assessed for olfactory and gustatory functions.

Loss of smell and taste are commonly reported symptoms associated with coronavirus disease 2019 (COVID-19); however, the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in people with acute loss of smell and/or taste is unknown. The study aimed to determine the seroprevalence of SARS-CoV-2 antibodies in a community-based population with acute loss of smell and/or taste and to compare the frequency of COVID-19 associated symptoms in participants with and without SARS-CoV-2 antibodies. It also evaluated whether smell or taste loss are indicative of COVID-19 infection. Text messages, sent via primary care centers in London, United Kingdom, invited people with loss of smell and/or taste in the preceding month, to participate. Recruitment took place between 23 April 2020 and 14 May 2020. A total of 590 participants enrolled via a web-based platform and responded to questions about loss of smell and taste and other COVID-19-related symptoms. Mean age was 39.4 years (SD ± 12.0) and 69.1% (n = 392) of participants were female. A total of 567 (96.1%) had a telemedicine consultation during which their COVID-19-related symptoms were verified and a lateral flow immunoassay test that detected SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies was undertaken under medical supervision. A total of 77.6% of 567 participants with acute smell and/or taste loss had SARS-CoV-2 antibodies; of these, 39.8% (n = 175) had neither cough nor fever. New loss of smell was more prevalent in participants with SARS-CoV-2 antibodies, compared with those without antibodies (93.4% versus 78.7%, p < 0.001), whereas taste loss was equally prevalent (90.2% versus 89.0%, p = 0.738). Seropositivity for SARS-CoV-2 was 3 times more likely in participants with smell loss (OR 2.86; 95% CI 1.27-6.36; p < 0.001) compared with those with taste loss. The limitations of this study are the lack of a general population control group, the self-reported nature of the smell and taste changes, and the fact our methodology does not take into account the possibility that a population subset may not seroconvert to develop SARS-CoV-2 antibodies post-COVID-19. Our findings suggest that recent loss of smell is a highly specific COVID-19 symptom and should be considered more generally in guiding case isolation, testing, and treatment of COVID-19. ClinicalTrials.gov NCT04377815.

Purpose To estimate long-term prognosis of chemosensory dysfunctions among patients recovering from COVID-19 disease. Methods Between April 2020 and July 2022, we conducted a prospective, observational study enrolling 48 patients who experienced smell and/or taste dysfunction during the acute-phase of COVID-19. Patients were evaluated for chemosensory function up to 24 months after disease onset. Results During the acute-phase of COVID-19, 80% of patients reported anosmia, 15% hyposmia, 63% ageusia, and 33% hypogeusia. At two years’ follow-up, 53% still experienced smell impairment, and 42% suffered from taste impairment. Moreover, 63% of patients who reported parosmia remained with olfactory disturbance. Interestingly, we found a negative correlation between visual analogue scale scores for smell and taste impairments during the acute-phase of COVID-19 and the likelihood of long-term recovery. Conclusion Our study sheds light on the natural history and long-term follow-up of chemosensory dysfunction in patients recovering from COVID-19 disease. Most patients who initially suffered from smell and/or taste disturbance did not reach full recovery after 2 years follow-up. The severity of impairment may serve as a prognostic indicator for full recovery.

ObjectiveThe purpose of the study is to compare the prevalence and associated risk factors of smell and/or taste disorders depending on different virus strains in Hiroshima, Japan.DesignA cross-sectional design was used.Setting and participantsData were collected for all COVID-19-confirmed inpatients admitted to 27 hospitals in Hiroshima prefecture, Japan, between 8 April 2020 and 31 January 2023.Main outcome measuresSmell and/or taste disorders were indicated by physicians on Hiroshima prefecture COVID-19 version J-SPEED forms completed at discharge.ResultsThe COVID-19 data from this period corresponds to the following four strains: Wild-dominant, Alpha-dominant, Delta-dominant and Omicron-dominant. A total of 11 353 confirmed cases were analysed and 1261 cases (11.11%) were reported for smell and/or taste disorders.Among patients with Wild-dominant, 241 out of 1141 cases (21.12%) exhibited smell and/or taste disorders. For Alpha, 223 out of 1265 cases (17.63%), for Delta, 480 out of 1516 cases (31.66%) and for Omicron, 317 out of 7431 cases (4.27%) presented with smell and/or taste disorders. For all four variants, age<65 (Wild: adjusted odds ratio [aOR]=2.66, 95% confidence interval [CI]:1.82–3.88; Alpha:aOR=2.00, 95%CI:1.39–2.88; Delta: aOR=2.42, 95%CI:1.54–3.81; Omicron: aOR=1.84, 95%CI:1.40–2.42) were related to smell and/or taste disorders. For the Wild and Delta variants, higher odds of reporting smell and/or taste disorders were found among wmen (Wild:aOR=1.63, 95%CI:1.20–2.22; Delta: aOR=1.41, 95%CI:1.10– 1.80).ConclusionsThe proportion of patients with smell and/or taste disorders varied significantly depending on the virus strain. Our findings indicate that the Delta-dominant period had the highest number of patients with these disorders, while the Omicron-dominant period had the lowest. Moreover, our study identified risk factors for smell and/or taste disorders for each variant.

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  <  0.001), however neither was clinically relevant. The correlation between chemosensitive scores and oxygen saturation was significant only for taste at T2 ( p  <  0.001). Logistic regression analysis found significant correlations between olfactory impairment severity and need for hospitalization at T2 (OR 3.750, 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.