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      Objective sensory testing methods reveal a higher prevalence of olfactory loss in COVID-19–positive patients compared to subjective methods: A systematic review and meta-analysis

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          Abstract

          Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has currently infected over 6.5 million people worldwide. In response to the pandemic, numerous studies have tried to identify causes and symptoms of the disease. Emerging evidence supports recently acquired anosmia (complete loss of smell) and hyposmia (partial loss of smell) as symptoms of COVID-19, but studies of olfactory dysfunction show a wide range of prevalence, from 5% to 98%. We undertook a search of Pubmed/Medline and Google Scholar with the keywords “COVID-19,” “smell,” and/or “olfaction.” We included any study that quantified olfactory loss as a symptom of COVID-19. Studies were grouped and compared based on the type of method used to measure smell loss—subjective measures such as self-reported smell loss versus objective measures using rated stimuli—to determine if prevalence rate differed by method type. For each study, 95% confidence intervals (CIs) were calculated from point estimates of olfactory disturbance rates. We identified 34 articles quantifying anosmia as a symptom of COVID-19, collected from cases identified from January 16 to April 30, 2020. The pooled prevalence estimate of smell loss was 77% when assessed through objective measurements (95% CI of 61.4–89.2%) and 45% with subjective measurements (95% CI of 31.1–58.5%). Objective measures are a more sensitive method to identify smell loss as a result of infection with SARS-CoV-2; the use of subjective measures, while expedient during the early stages of the pandemic, underestimates the true prevalence of smell loss.

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          Quantifying heterogeneity in a meta-analysis.

          The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.
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            Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.

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              SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes

              We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells' potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
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                Author and article information

                Journal
                medRxiv
                MEDRXIV
                medRxiv
                Cold Spring Harbor Laboratory
                06 July 2020
                : 2020.07.04.20145870
                Affiliations
                [1 ]Monell Chemical Senses Center, 3500 Market St, Philadelphia PA 19104
                [2 ]Division of Intramural Research, National Institute of Nursing Research, National Institutes of Health, Bethesda, MD, USA
                [3 ]Division of Intramural Research, National Institute of Nursing Research & National Institute of Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
                Author notes

                Monell Chemical Senses Center, 3500 Market St, Philadelphia PA 19104

                [*]

                These authors contributed equally to this work.

                Please address correspondence: Danielle R. Reed, Ph.D., Monell Chemical Senses Center, Philadelphia PA 19104, 267-519-4915, reed@ 123456monell.org
                Article
                10.1101/2020.07.04.20145870
                7359533
                32676608
                19082ca2-9378-454f-bb31-d907e706a2d3

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.

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                covid-19,coronavirus,anosmia,olfactory dysfunction,sars-cov-2

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