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Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms.

ABSTRACT: COVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2/TMPRSS2 proteins, has been reported in non-chemosensory cells in the rodent's nose and mouth, missing a direct correlation between the symptoms reported in patients and the observed direct viral infection in human sensory cells. Here, mapping the gene and protein expression of ACE2/TMPRSS2 in the mouse olfactory and gustatory cells, we precisely identify the virus target cells to be of basal and sensory origin and reveal the age-dependent appearance of viral entry-sites. Our results propose an alternative interpretation of the human viral-induced sensory symptoms and give investigative perspectives on animal models.

SUBMITTER: Brechbuhl J

PROVIDER: S-EPMC8282876 | biostudies-literature | 2021 Jul

REPOSITORIES: biostudies-literature

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Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms.

Brechbühl Julien J Lopes Ana Catarina AC Wood Dean D Bouteiller Sofiane S de Vallière Aurélie A Verdumo Chantal C Broillet Marie-Christine MC

Communications biology 20210715 1

COVID-19 pandemic has given rise to a collective scientific effort to study its viral causing agent SARS-CoV-2. Research is focusing in particular on its infection mechanisms and on the associated-disease symptoms. Interestingly, this environmental pathogen directly affects the human chemosensory systems leading to anosmia and ageusia. Evidence for the presence of the cellular entry sites of the virus, the ACE2/TMPRSS2 proteins, has been reported in non-chemosensory cells in the rodent's nose an ...[more]

PMID: 34267318

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Project description:BackgroundNeurological symptoms are frequent among patients with COVID-19. Little is known regarding the repercussions of neurological symptoms for patients and how these symptoms are related to one another.ObjectivesTo determine whether there is an association between the neurological symptoms in patients with COVID-19, and to characterize the headache.MethodThis was a cross-sectional study. All hospital inpatients and health workers at the Hospital Universitario Oswaldo Cruz with a PCR-confirmed COVID-19 infection between March and June 2020 were considered for the study and were interviewed by telephone at least 2-months after the acute phase of the disease. These patients were identified by the hospital epidemiological surveillance department. A semi-structured questionnaire was used containing sociodemographic and clinical data and the ID-Migraine.ResultsA total of 288 patients was interviewed; 53.1% were male; with a median age of 49.9 (41.5-60.5) years; 91.7% presented some neurological symptom; 22.2% reported some neurological symptom as the symptom that troubled them most during COVID-19. Neurological symptoms were: ageusia (69.8%), headache (69.1%), anosmia (67%), myalgia (44.4%), drowsiness (37.2%), agitation (20.8%); mental confusion (14.9%), syncope (4.9%) and epileptic seizures (2.8%). Females, those who presented with fever, sore throat, anosmia/ageusia and myalgia also presented significantly more with headache (logistic regression). The most frequent headache phenotype was a non-migraine phenotype, was of severe intensity and differed from previous headaches. This persisted for more than 30 days in 18% and for more than 90 days in 10% of patients. Thirteen percent of those with anosmia and 11% with ageusia continued with these complaints after more than 90 days of the acute phase of the disease. Aged over 50 years, agitation and epileptic seizures were significantly associated with mental confusion (logistic regression).ConclusionHeadache is frequent in COVID-19, is associated with other symptoms such as fever, sore throat, anosmia, ageusia, and myalgia, and may persist beyond the acute phase of the disease.

Project description:BackgroundDuring the unprecedented COVID-19 pandemic, social media has been extensively used to amplify the spread of information and to express personal health-related experiences regarding symptoms, including anosmia and ageusia, 2 symptoms that have been reported later than other symptoms.ObjectiveOur objective is to investigate to what extent Twitter users reported anosmia and ageusia symptoms in their tweets and if they connected them to COVID-19, to evaluate whether these symptoms could have been identified as COVID-19 symptoms earlier using Twitter rather than the official notice.MethodsWe collected French tweets posted between January 1, 2020, and March 31, 2020, containing anosmia- or ageusia-related keywords. Symptoms were detected using fuzzy matching. The analysis consisted of 3 parts. First, we compared the coverage of anosmia and ageusia symptoms in Twitter and in traditional media to determine if the association between COVID-19 and anosmia or ageusia could have been identified earlier through Twitter. Second, we conducted a manual analysis of anosmia- and ageusia-related tweets to obtain quantitative and qualitative insights regarding their nature and to assess when the first associations between COVID-19 and these symptoms were established. We randomly annotated tweets from 2 periods: the early stage and the rapid spread stage of the epidemic. For each tweet, each symptom was annotated regarding 3 modalities: symptom (yes or no), associated with COVID-19 (yes, no, or unknown), and whether it was experienced by someone (yes, no, or unknown). Third, to evaluate if there was a global increase of tweets mentioning anosmia or ageusia in early 2020, corresponding to the beginning of the COVID-19 epidemic, we compared the tweets reporting experienced anosmia or ageusia between the first periods of 2019 and 2020.ResultsIn total, 832 (respectively 12,544) tweets containing anosmia (respectively ageusia) related keywords were extracted over the analysis period in 2020. The comparison to traditional media showed a strong correlation without any lag, which suggests an important reactivity of Twitter but no earlier detection on Twitter. The annotation of tweets from 2020 showed that tweets correlating anosmia or ageusia with COVID-19 could be found a few days before the official announcement. However, no association could be found during the first stage of the pandemic. Information about the temporality of symptoms and the psychological impact of these symptoms could be found in the tweets. The comparison between early 2020 and early 2019 showed no difference regarding the volumes of tweets.ConclusionsBased on our analysis of French tweets, associations between COVID-19 and anosmia or ageusia by web users could have been found on Twitter just a few days before the official announcement but not during the early stage of the pandemic. Patients share qualitative information on Twitter regarding anosmia or ageusia symptoms that could be of interest for future analyses.

Project description:BackgroundMultiple 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.MethodsFor 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.FindingsBetween 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.InterpretationThe 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.FundingNational Institutes of Health, National Institute for Health Research, Alzheimer's Society, Wellcome Trust, and Massachusetts Consortium on Pathogen Readiness.

Project description:ObjectiveWhile many seroprevalence studies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been performed, few are demographically representative. This investigation focused on defining the nature and frequency of symptomatic and asymptomatic SARS-CoV-2 infection in a representative, cross-sectional sample of communities in Louisiana, USA.MethodsA sample of 4778 adults from New Orleans and Baton Rouge, Louisiana were given a survey of symptoms and co-morbidities, nasopharyngeal swab to test for active infection (PCR), and blood draw to test for past infection (IgG). Odds ratios, cluster analysis, quantification of virus and antibody, and linear modelling were used to understand whether certain symptoms were associated with a positive test, how symptoms grouped together, whether virus or antibody varied by symptom status, and whether being symptomatic was different across the age span.ResultsReported anosmia/ageusia was strongly associated with a positive test; 40.6% (93/229) tested positive versus 4.8% (218/4549) positivity in those who did not report anosmia/ageusia (OR 13.6, 95% CI 10.1-18.3). Of the people who tested positive, 47.3% (147/311) were completely asymptomatic. Symptom presentation clustered into three groups; low/no symptoms (0.4 ± 0.9, mean ± SD), highly symptomatic (7.5 ± 1.9) or moderately symptomatic (4.0 ± 1.5). Quantity of virus was lower in the asymptomatic versus symptomatic group (cycle number 23.3 ± 8.3 versus 17.3 ± 9.0; p < 0.001). Modelling the probability of symptoms showed changes with age; the highest probability of reporting symptoms was 64.6% (95% CI 50.4-76.5) at age 29 years, which decreased to a probability of 49.3% (95% CI 36.6-62.0) at age 60 years and only 25.1% (95% CI 5.0-68.1) at age 80 years.ConclusionAnosmia/ageusia can be used to differentiate SARS-CoV-2 infection from other illnesses, and, given the high ratio of asymptomatic individuals, contact tracing should include those without symptoms. Regular testing in congregant settings of those over age 60 years may help mitigate asymptomatic spread.

Dataset Information

Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms.

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Age-dependent appearance of SARS-CoV-2 entry sites in mouse chemosensory systems reflects COVID-19 anosmia-ageusia symptoms.

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