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1. Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms

Author

Gerkin, Richard, Ohla, Kathrin, Veldhuizen, Maria, Joseph, Paule, Kelly, Christine, Bakke, Alyssa, Steele, Kimberley, Farruggia, Michael, Pellegrino, Robert, Pepino, Marta, Bouysset, Cédric, Soler, Graciela, Pereda-Loth, Veronica, Dibattista, Michele, Cooper, Keiland, Croijmans, Ilja, Di Pizio, Antonella, Ozdener, Mehmet Hakan, Fjaeldstad, Alexander, Lin, Cailu, Sandell, Mari, Singh, Preet, Brindha, Evelyn, Olsson, Shannon, Saraiva, Luis, Ahuja, Gaurav, Alwashahi, Mohammed, Bhutani, Surabhi, D’Errico, Anna, Fornazieri, Marco, Golebiowski, Jérôme, Dar Hwang, Liang, Öztürk, Lina, Roura, Eugeni, Spinelli, Sara, Whitcroft, Katherine, Faraji, Farhoud, Fischmeister, Florian, Heinbockel, Thomas, Hsieh, Julien, Huart, Caroline, Konstantinidis, Iordanis, Menini, Anna, Morini, Gabriella, Olofsson, Jonas, Philpott, Carl, Pierron, Denis, Shields, Vonnie, Voznessenskaya, Vera, Albayay, Javier, Altundag, Aytug, Bensafi, Moustafa, Bock, María Adelaida, Calcinoni, Orietta, Fredborg, William, Laudamiel, Christophe, Lim, Juyun, Lundström, Johan, Macchi, Alberto, Meyer, Pablo, Moein, Shima, Santamaría, Enrique, Sengupta, Debarka, Rohlfs Dominguez, Paloma, Yanik, Hüseyin, Hummel, Thomas, Hayes, John, Reed, Danielle, Niv, Masha, Munger, Steven, Parma, Valentina, Boesveldt, Sanne, de Groot, Jasper, Dinnella, Caterina, Freiherr, Jessica, Laktionova, Tatiana, Marino, Sajidxa, Monteleone, Erminio, Nunez-Parra, Alexia, Abdulrahman, Olagunju, Ritchie, Marina, Thomas-Danguin, Thierry, Walsh-Messinger, Julie, Al Abri, Rashid, Alizadeh, Rafieh, Bignon, Emmanuelle, Cantone, Elena, Paola Cecchini, Maria, Chen, Jingguo, Dolors Guàrdia, Maria, Hoover, Kara, Karni, Noam, Navarro, Marta, Nolden, Alissa, Portillo Mazal, Patricia, Rowan, Nicholas, Sarabi-Jamab, Atiye, Archer, Nicholas, Chen, Ben, Di Valerio, Elizabeth, Feeney, Emma, Frasnelli, Johannes, Hannum, Mackenzie, Hopkins, Claire, Klein, Hadar, Mignot, Coralie, Mucignat, Carla, Ning, Yuping, Ozturk, Elif, Peng, Mei, Saatci, Ozlem, Sell, Elizabeth, Yan, Carol, Alfaro, Raul, Coureaud, G., Herriman, Riley, Justice, Jeb, Kaushik, Pavan Kumar, Koyama, Sachiko, Overdevest, Jonathan, Pirastu, Nicola, Ramirez, Vicente, Roberts, S. Craig, Smith, Barry, Cao, Hongyuan, Wang, Hong, Balungwe Birindwa, Patrick, Baguma, Marius, Ozdener, Mehmet, Bock, María, Kaushik, Pavan, Pizio, Antonella, Hakan Ozdener, Mehmet, D'Errico, Anna, Hwang, Liang Dar, Group, GCCR, Cecchini, Maria, Indústries Alimentàries, Qualitat i Tecnologia Alimentària, Arizona State University [Tempe] (ASU), Forschungszentrum Jülich GmbH | Centre de recherche de Juliers, Helmholtz-Gemeinschaft = Helmholtz Association, Mersin University, National Institutes of Health [Bethesda] (NIH), AbScent, Pennsylvania State University (Penn State), Penn State System, Yale University [New Haven], University of Tennessee, University of Illinois at Urbana-Champaign [Urbana], University of Illinois System, Institut de Chimie de Nice (ICN), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Buenos Aires University and GEOG (Grupo de Estudio de Olfato y Gusto), Centre d'anthropologie et de génomique de Toulouse (CAGT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Bari Aldo Moro (UNIBA), University of California, Utrecht University [Utrecht], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Monell Chemical Senses Center, Regional Hospital West Jutland [Denmark], University of Helsinki, University of Oslo (UiO), Karunya Institute of Technology and Sciences, Tata Institute of Fundamental Research, Sidra Medicine [Doha, Qatar], Indraprastha Institute of Information Technology [New Delhi] (IIIT-Delhi), Sultan Qaboos University (SQU), San Diego State University (SDSU), Goethe-University Frankfurt am Main, State University of Londrina = Universidade Estadual de Londrina, Elena Cantone, University of Queensland - The Diamantina Institute, University of Queensland [Brisbane], Università degli Studi di Firenze = University of Florence [Firenze] (UNIFI), University College of London [London] (UCL), UC San Diego Health, Karl-Franzens-Universität [Graz, Autriche], Howard University College of Medicine [Washington, DC, USA], Geneva University Hospitals and Geneva University, Cliniques Universitaires Saint-Luc [Bruxelles], Aristotle University of Thessaloniki, Scuola Internazionale Superiore di Studi Avanzati / International School for Advanced Studies (SISSA / ISAS), Stockholm University, University of East Anglia [Norwich] (UEA), Towson University [Towson, MD, United States], University of Maryland System, Severtsov Institute of Ecology and Evolution RAS, University of Padova [Padova, Italy], Biruni University, Centre de recherche en neurosciences de Lyon (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospital General de Barrio Obrero [Asunción, Paraguay] (Public Hospital Barrio Obrero ), Private practice [Milan], DreamAir Llc, Oregon State University (OSU), Karolinska Institutet [Stockholm], University of Insubria, Varese, IBM Watson Research Center, IBM, Navarrabiomed-IdiSNA, University of Extremadura, Technische Universität Dresden = Dresden University of Technology (TU Dresden), The Hebrew University of Jerusalem (HUJ), University of Florida [Gainesville] (UF), Temple University [Philadelphia], Pennsylvania Commonwealth System of Higher Education (PCSHE), Wageningen University and Research [Wageningen] (WUR), Radboud university [Nijmegen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Universidad de Chile = University of Chile [Santiago] (UCHILE), Federal University of Technology of Akure (FUTA), University of California [Berkeley], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Bourgogne Franche-Comté [COMUE] (UBFC), University of Dayton, Iran University of Medical Sciences [Tehran, Iran] (IUMS), 'Federico II' University of Naples Medical School, University of Verona (UNIVR), Xi'an Jiaotong University (Xjtu), Institute of Agrifood Research and Technology (IRTA), University of Alaska [Fairbanks] (UAF), The Hebrew University Medical Center, University of Massachusetts System (UMASS), Instituto Universitario del Hospital Italiano [Buenos Aires, Argentina], Johns Hopkins University School of Medicine [Baltimore], Institute for Research in Fundamental Sciences [Tehran] (IPM), CSIRO Agriculture and Food (CSIRO), The First Affiliated Hospital of Guangzhou Medical University (GMU), University College Dublin [Dublin] (UCD), Université du Québec à Trois-Rivières (UQTR), Guy’s and St. Thomas’ Hospitals, University of Padova, Kilis Yedi Aralik University, University of Otago [Dunedin, Nouvelle-Zélande], Sancaktepe Education and Research Hospital, University of Pennsylvania [Philadelphia], University of California San Diego Health, Indiana University [Bloomington], Indiana University System, Columbia University Medical Center (CUMC), Columbia University [New York], University of Edinburgh, University of California [Merced], University of Stirling, University of London [London], Florida State University [Tallahassee] (FSU), Université catholique de Bukavu, University of Southern Queensland (USQ), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Technical University of Munich (TUM), University of Graz, Publica, Gerkin, Richard C, Ohla, Kathrin, Veldhuizen, Maria G, Joseph, Paule V, Kelly, Christine E, Bakke, Alyssa J, Steele, Kimberley E, Farruggia, Michael C, Pellegrino, Robert, Pepino, Marta Y, Bouysset, Cédric, Soler, Graciela M, Pereda-Loth, Veronica, Dibattista, Michele, Cooper, Keiland W, Croijmans, Ilja, Di Pizio, Antonella, Ozdener, M Hakan, Fjaeldstad, Alexander W, Lin, Cailu, Sandell, Mari A, Singh, Preet B, Brindha, V Evelyn, Olsson, Shannon B, Saraiva, Luis R, Ahuja, Gaurav, Alwashahi, Mohammed K, Bhutani, Surabhi, D'Errico, Anna, Fornazieri, Marco A, Golebiowski, Jérôme, Hwang, Liang-Dar, Öztürk, Lina, Roura, Eugeni, Spinelli, Sara, Whitcroft, Katherine L, Faraji, Farhoud, Fischmeister, Florian PhS, Heinbockel, Thoma, Hsieh, Julien W, Huart, Caroline, Konstantinidis, Iordani, Menini, Anna, Morini, Gabriella, Olofsson, Jonas K, Philpott, Carl M, Pierron, Deni, Shields, Vonnie D C, Voznessenskaya, Vera V, Albayay, Javier, Altundag, Aytug, Bensafi, Moustafa, Bock, María Adelaida, Calcinoni, Orietta, Fredborg, William, Laudamiel, Christophe, Lim, Juyun, Lundström, Johan N, Macchi, Alberto, Meyer, Pablo, Moein, Shima T, Santamaría, Enrique, Sengupta, Debarka, Dominguez, Paloma Rohlf, Yanik, Hüseyin, Hummel, Thoma, Hayes, John E, Reed, Danielle R, Niv, Masha Y, Munger, Steven D, Parma, Valentina, Tıp Fakültesi, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service d'oto-rhino-laryngologie

Subjects
Male, Multivariate statistics, Physiology, Cross-sectional study, [SDV]Life Sciences [q-bio], coronavirus, Logistic regression, Settore BIO/09 - Fisiologia, Behavioral Neuroscience, 0302 clinical medicine, Hyposmia, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, 030223 otorhinolaryngology, Sensory Science and Eating Behaviour, Chemosensory, hyposmia, Middle Aged, Prognosis, olfactory, Sensory Systems, Smell, chemosensory, ddc:540, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Female, HEALTH, medicine.symptom, Adult, medicine.medical_specialty, Anosmia, Coronavirus, Olfactory, Prediction, COVID-19, Cross-Sectional Studies, Humans, SARS-CoV-2, Self Report, 663/664, Visual analogue scale, Odds, 03 medical and health sciences, Physiology (medical), Internal medicine, QUALITY, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, COVID-19 symptoms, Behaviour Change and Well-being, IDENTIFICATION, business.industry, Univariate, prediction, Sensoriek en eetgedrag, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, anosmia, Smell impairment
Abstract

Contains fulltext : 228204.pdf (Publisher’s version ) (Closed access) In a preregistered, cross-sectional study we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n=4148) or negative (C19-; n=546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean±SD, C19+: -82.5±27.2 points; C19-: -59.8±37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC=0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4

Published
2020

2. More than smell - COVID-19 is associated with severe impairment of smell, taste, and chemesthesis

Author

Parma, Valentina, Ohla, Kathrin, Veldhuizen, Maria G, Niv, Masha Y, Kelly, Christine E, Bakke, Alyssa J, Cooper, Keiland W, Bouysset, Cédric, Pirastu, Nicola, Dibattista, Michele, Kaur, Rishemjit, Liuzza, Marco Tullio, Pepino, Marta Y, Schöpf, Veronika, and Roberts, S Craig

Abstract

Recent anecdotal and scientific reports have provided evidence of a link between COVID-19 and chemosensory impairments such as anosmia. However, these reports have downplayed or failed to distinguish potential effects on taste, ignored chemesthesis, generally lacked quantitative measurements, were mostly restricted to data from single countries. Here, we report the development, implementation and initial results of a multi-lingual, international questionnaire to assess self-reported quantity and quality of perception in three distinct chemosensory modalities (smell, taste, and chemesthesis) before and during COVID-19. In the first 11 days after questionnaire launch, 4039 participants (2913 women, 1118 men, 8 other, ages 19-79) reported a COVID-19 diagnosis either via laboratory tests or clinical assessment. Importantly, smell, taste and chemesthetic function were each significantly reduced compared to their status before the disease. Difference scores (maximum possible change+/-100) revealed a mean reduction of smell (-79.7+/- 28.7, mean+/- SD), taste (-69.0+/- 32.6), and chemesthetic (-37.3+/- 36.2) function during COVID-19. Qualitative changes in olfactory ability (parosmia and phantosmia) were relatively rare and correlated with smell loss. Importantly, perceived nasal obstruction did not account for smell loss. Furthermore, chemosensory impairments were similar between participants in the laboratory test and clinical assessment groups. These results show that COVID-19-associated chemosensory impairment is not limited to smell, but also affects taste and chemesthesis. The multimodal impact of COVID-19 and lack of perceived nasal obstruction suggest that SARS-CoV-2 infection may disrupt sensory-neural mechanisms.

Published
2020

3. Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms.

Author

Gerkin RC, Ohla K, Veldhuizen MG, Joseph PV, Kelly CE, Bakke AJ, Steele KE, Farruggia MC, Pellegrino R, Pepino MY, Bouysset C, Soler GM, Pereda-Loth V, Dibattista M, Cooper KW, Croijmans I, Di Pizio A, Ozdener MH, Fjaeldstad AW, Lin C, Sandell MA, Singh PB, Brindha VE, Olsson SB, Saraiva LR, Ahuja G, Alwashahi MK, Bhutani S, D'Errico A, Fornazieri MA, Golebiowski J, Dar Hwang L, Öztürk L, Roura E, Spinelli S, Whitcroft KL, Faraji F, Fischmeister FPS, Heinbockel T, Hsieh JW, Huart C, Konstantinidis I, Menini A, Morini G, Olofsson JK, Philpott CM, Pierron D, Shields VDC, Voznessenskaya VV, Albayay J, Altundag A, Bensafi M, Bock MA, Calcinoni O, Fredborg W, Laudamiel C, Lim J, Lundström JN, Macchi A, Meyer P, Moein ST, Santamaría E, Sengupta D, Rohlfs Dominguez P, Yanik H, Hummel T, Hayes JE, Reed DR, Niv MY, Munger SD, and Parma V

Subjects
Adult, Anosmia etiology, COVID-19 complications, Cross-Sectional Studies, Female, Humans, Male, Middle Aged, Prognosis, SARS-CoV-2 isolation & purification, Self Report, Smell, Anosmia diagnosis, COVID-19 diagnosis
Abstract

In a preregistered, cross-sectional study, we investigated whether olfactory loss is a reliable predictor of COVID-19 using a crowdsourced questionnaire in 23 languages to assess symptoms in individuals self-reporting recent respiratory illness. We quantified changes in chemosensory abilities during the course of the respiratory illness using 0-100 visual analog scales (VAS) for participants reporting a positive (C19+; n = 4148) or negative (C19-; n = 546) COVID-19 laboratory test outcome. Logistic regression models identified univariate and multivariate predictors of COVID-19 status and post-COVID-19 olfactory recovery. Both C19+ and C19- groups exhibited smell loss, but it was significantly larger in C19+ participants (mean ± SD, C19+: -82.5 ± 27.2 points; C19-: -59.8 ± 37.7). Smell loss during illness was the best predictor of COVID-19 in both univariate and multivariate models (ROC AUC = 0.72). Additional variables provide negligible model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms (e.g., fever). Olfactory recovery within 40 days of respiratory symptom onset was reported for ~50% of participants and was best predicted by time since respiratory symptom onset. We find that quantified smell loss is the best predictor of COVID-19 amongst those with symptoms of respiratory illness. To aid clinicians and contact tracers in identifying individuals with a high likelihood of having COVID-19, we propose a novel 0-10 scale to screen for recent olfactory loss, the ODoR-19. We find that numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (4 < OR < 10). Once independently validated, this tool could be deployed when viral lab tests are impractical or unavailable., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2021
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4. Corrigendum to: More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis.

Author

Parma V, Ohla K, Veldhuizen MG, Niv MY, Kelly CE, Bakke AJ, Cooper KW, Bouysset C, Pirastu N, Dibattista M, Kaur R, Liuzza MT, Pepino MY, Schöpf V, Pereda-Loth V, Olsson SB, Gerkin RC, Rohlfs Domínguez P, Albayay J, Farruggia MC, Bhutani S, Fjaeldstad AW, Kumar R, Menini A, Bensafi M, Sandell M, Konstantinidis I, Di Pizio A, Genovese F, Öztürk L, Thomas-Danguin T, Frasnelli J, Boesveldt S, Saatci Ö, Saraiva LR, Lin C, Golebiowski J, Hwang LD, Ozdener MH, Guàrdia MD, Laudamiel C, Ritchie M, Havlícek J, Pierron D, Roura E, Navarro M, Nolden AA, Lim J, Whitcroft KL, Colquitt LR, Ferdenzi C, Brindha EV, Altundag A, Macchi A, Nunez-Parra A, Patel ZM, Fiorucci S, Philpott CM, Smith BC, Lundström JN, Mucignat C, Parker JK, van den Brink M, Schmuker M, Fischmeister FPS, Heinbockel T, Shields VDC, Faraji F, Santamaría E, Fredborg WEA, Morini G, Olofsson JK, Jalessi M, Karni N, D'Errico A, Alizadeh R, Pellegrino R, Meyer P, Huart C, Chen B, Soler GM, Alwashahi MK, Welge-Lüssen A, Freiherr J, de Groot JHB, Klein H, Okamoto M, Singh PB, Hsieh JW, Reed DR, Hummel T, Munger SD, and Hayes JE

Published
2021
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5. Metal Ions Activate the Human Taste Receptor TAS2R7.

Author

Wang Y, Zajac AL, Lei W, Christensen CM, Margolskee RF, Bouysset C, Golebiowski J, Zhao H, Fiorucci S, and Jiang P

Subjects
Administration, Oral, Aluminum administration & dosage, Aluminum chemistry, Calcium administration & dosage, Calcium chemistry, Humans, Metals, Heavy administration & dosage, Metals, Heavy chemistry, Models, Molecular, Mutagenesis, Site-Directed, Receptors, G-Protein-Coupled chemistry, Receptors, G-Protein-Coupled genetics, Aluminum pharmacology, Calcium pharmacology, Metals, Heavy pharmacology, Receptors, G-Protein-Coupled metabolism
Abstract

Divalent and trivalent salts exhibit a complex taste profile. They are perceived as being astringent/drying, sour, bitter, and metallic. We hypothesized that human bitter-taste receptors may mediate some taste attributes of these salts. Using a cell-based functional assay, we found that TAS2R7 responds to a broad range of divalent and trivalent salts, including zinc, calcium, magnesium, copper, manganese, and aluminum, but not to potassium, suggesting TAS2R7 may act as a metal cation receptor mediating bitterness of divalent and trivalent salts. Molecular modeling and mutagenesis analysis identified 2 residues, H943.37 and E2647.32, in TAS2R7 that appear to be responsible for the interaction of TAS2R7 with metallic ions. Taste receptors are found in both oral and extraoral tissues. The responsiveness of TAS2R7 to various mineral salts suggests it may act as a broad sensor, similar to the calcium-sensing receptor, for biologically relevant metal cations in both oral and extraoral tissues., (© The Author(s) 2019. Published by Oxford University Press.)

Published
2019
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