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[Preprint]. 2020 Jul 28:2020.07.22.20157263. Originally published 2020 Jul 26. [Version 2] doi: 10.1101/2020.07.22.20157263

The best COVID-19 predictor is recent smell loss: a cross-sectional study

Richard C Gerkin, Kathrin Ohla, Maria Geraldine Veldhuizen, Paule V Joseph, Christine E Kelly, Alyssa J Bakke, Kimberley E Steele, Michael C Farruggia, Robert Pellegrino, Marta Y Pepino, Cédric Bouysset, Graciela M Soler, Veronica Pereda-Loth, Michele Dibattista, Keiland W Cooper, Ilja Croijmans, Antonella Di Pizio, M Hakan Ozdener, Alexander W Fjaeldstad, Cailu Lin, Mari A Sandell, Preet B Singh, V Evelyn Brindha, Shannon B Olsson, Luis R Saraiva, Gaurav Ahuja, Mohammed K Alwashahi, Surabhi Bhutani, Anna D'Errico, Marco A Fornazieri, Jérôme Golebiowski, Liang-Dar Hwang, Lina Öztürk, Eugeni Roura, Sara Spinelli, Katherine L Whitcroft, Farhoud Faraji, Florian PhS Fischmeister, Thomas Heinbockel, Julien W Hsieh, Caroline Huart, Iordanis Konstantinidis, Anna Menini, Gabriella Morini, Jonas K Olofsson, Carl M Philpott, Denis Pierron, Vonnie D C Shields, Vera V Voznessenskaya, Javier Albayay, Aytug Altundag, Moustafa Bensafi, María Adelaida Bock, Orietta Calcinoni, William Fredborg, Christophe Laudamiel, Juyun Lim, Johan N Lundström, Alberto Macchi, Pablo Meyer, Shima T Moein, Enrique Santamaría, Debarka Sengupta, Paloma Paloma Domínguez, Hüseyin Yanık, Sanne Boesveldt, Jasper H B de Groot, Caterina Dinnella, Jessica Freiherr, Tatiana Laktionova, Sajidxa Mariño, Erminio Monteleone, Alexia Nunez-Parra, Olagunju Abdulrahman, Marina Ritchie, Thierry Thomas-Danguin, Julie Walsh-Messinger, Rashid Al Abri, Rafieh Alizadeh, Emmanuelle Bignon, Elena Cantone, Maria Paola Cecchini, Jingguo Chen, Maria Dolors Guàrdia, Kara C Hoover, Noam Karni, Marta Navarro, Alissa A Nolden, Patricia Portillo Mazal, Nicholas R Rowan, Atiye Sarabi-Jamab, Nicholas S Archer, Ben Chen, Elizabeth A Di Valerio, Emma L Feeney, Johannes Frasnelli, Mackenzie Hannum, Claire Hopkins, Hadar Klein, Coralie Mignot, Carla Mucignat, Yuping Ning, Elif E Ozturk, Mei Peng, Ozlem Saatci, Elizabeth A Sell, Carol H Yan, Raul Alfaro, Cinzia Cecchetto, Gérard Coureaud, Riley D Herriman, Jeb M Justice, Pavan Kumar Kaushik, Sachiko Koyama, Jonathan B Overdevest, Nicola Pirastu, Vicente A Ramirez, S Craig Roberts, Barry C Smith, Hongyuan Cao, Hong Wang, Patrick Balungwe, Marius Baguma, Thomas Hummel, John E Hayes, Danielle R Reed, Masha Y Niv, Steven D Munger, Valentina Parma
PMCID: PMC7386529  PMID: 32743605

Abstract

Background: COVID-19 has heterogeneous manifestations, though one of the most common symptoms is a sudden loss of smell (anosmia or hyposmia). We investigated whether olfactory loss is a reliable predictor of COVID-19. Methods: This preregistered, cross-sectional study used 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 singular and cumulative predictors of COVID-19 status and post-COVID-19 olfactory recovery. Results: 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 single and cumulative feature models (ROC AUC=0.72), with additional features providing no significant model improvement. VAS ratings of smell loss were more predictive than binary chemosensory yes/no-questions or other cardinal symptoms, such as fever or cough. Olfactory recovery within 40 days was reported for ~50% of participants and was best predicted by time since illness onset. Conclusions: As smell loss is the best predictor of COVID-19, we developed the ODoR-19 tool, a 0-10 scale to screen for recent olfactory loss. Numeric ratings ≤2 indicate high odds of symptomatic COVID-19 (10<OR<4), especially when viral lab tests are impractical or unavailable.

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