Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms

Richard C. Gerkin (1) , Kathrin Ohla (2) , Maria G. Veldhuizen (3) , Paule V. Joseph (4) , Christine E. Kelly (5) , Alyssa J. Bakke (6) , Kimberley E. Steele (4) , Michael C. Farruggia (7) , Robert Pellegrino (8) , Marta Y. Pepino (9) , Cédric Bouysset (10) , Graciela M. Soler (11) , Veronica Pereda-Loth (12) , Michele Dibattista (13) , Keiland W. Cooper (14) , Ilja Croijmans (15) , Antonella Di Pizio (16) , Mehmet Hakan Ozdener (17) , Alexander W. Fjaeldstad (18) , Cailu Lin (17) , Mari A. Sandell (19) , Preet B. Singh (20) , Evelyn Brindha (21) , Shannon B. Olsson (22) , Luis R. Saraiva (23) , Gaurav Ahuja (24) , Mohammed K. Alwashahi (25) , Surabhi Bhutani (26) , Anna D’errico (27) , Marco A. Fornazieri (28) , Jérôme Golebiowski (29) , Liang Dar Hwang (30) , Lina Öztürk (3) , Eugeni Roura (31) , Sara Spinelli (32) , Katherine L. Whitcroft (33) , Farhoud Faraji (34) , Florian Ph. S. Fischmeister (35) , Thomas Heinbockel (36) , Julien W. Hsieh (37) , Caroline Huart (38) , Iordanis Konstantinidis (39) , Anna Menini (40) , Gabriella Morini (41) , Jonas K. Olofsson (41) , Carl M. Philpott (42) , Denis Pierron (12) , Vonnie D. C. Shields (43) , Vera V. Voznessenskaya (44) , Javier Albayay (45) , Aytug Altundag (46) , Moustafa Bensafi (47) , María Adelaida Bock (48) , Orietta Calcinoni (49) , William Fredborg (41) , Christophe Laudamiel (50) , Juyun Lim (51) , Johan N. Lundström (52) , Alberto Macchi (53) , Pablo Meyer (54) , Shima T. Moein (55) , Enrique Santamaría (55) , Debarka Sengupta (24) , Paloma Rohlfs Dominguez (56) , Hüseyin Yanik (3) , Thomas Hummel (57) , John E. Hayes (6) , Danielle R. Reed (17) , Masha Y. Niv (58) , Steven D. Munger (59) , Valentina Parma (60) , Sanne Boesveldt (61) , Jasper H. B. de Groot (62) , Caterina Dinnella (32) , Jessica Freiherr (63) , Tatiana Laktionova (45) , Sajidxa Marino (64) , Erminio Monteleone (32) , Alexia Nunez-Parra (64) , Olagunju Abdulrahman (65) , Marina Ritchie (66) , Thierry Thomas-Danguin (67, 68) , Julie Walsh-Messinger (69) , Rashid Al Abri (25) , Rafieh Alizadeh (70) , Emmanuelle Bignon (10) , Elena Cantone (71) , Maria Paola Cecchini (72) , Jingguo Chen (73) , Maria Dolors Guàrdia (74) , Kara C. Hoover (75) , Noam Karni (76) , Marta Navarro (31) , Alissa A. Nolden (77) , Patricia Portillo Mazal (78) , Nicholas R. Rowan (79) , Atiye Sarabi-Jamab (80) , Nicholas S. Archer (81) , Ben Chen (82) , Elizabeth A. Di Valerio (59) , Emma L. Feeney (83) , Johannes Frasnelli (84) , Mackenzie E Hannum (17) , Claire Hopkins (85) , Hadar Klein (58) , Coralie Mignot (57) , Carla Mucignat (45) , Yuping Ning (82) , Elif E. Ozturk (86) , Mei Peng (87) , Ozlem Saatci (88) , Elizabeth A. Sell (89) , Carol H. Yan (90) , Raul Alfaro (9) , G. Coureaud (47) , Riley D. Herriman (17) , Jeb M. Justice (59) , Pavan Kumar Kaushik (91) , Sachiko Koyama (92) , Jonathan B. Overdevest (93) , Nicola Pirastu (94) , Vicente A. Ramirez (95) , S. Craig Roberts (96) , Barry C. Smith (97) , Hongyuan Cao (98) , Hong Wang (17) , Patrick Balungwe Birindwa (99) , Marius Baguma (99) , Mehmet Hakan Ozdener (17) , Florian Ph.S Fischmeister (35) , María Adelaida Bock (48) , Pavan Kumar Kaushik (91) , Antonella Di Pizio (16) , Mehmet Hakan Ozdener (17) , Preet B. Singh (20) , Anna d'Errico (27) , Liang Dar Hwang (100) , Gccr Group , Maria Paola Cecchini (72) , Elizabeth A. Di Valerio (59) , Loïc Briand (67) , Sophie Nicklaus (67) , Charlotte Sinding (67) , Anne Tromelin (67)

1 ASU - Arizona State University [Tempe]
2 Forschungszentrum Jülich GmbH | Centre de recherche de Juliers
3 Mersin University
4 NIH - National Institutes of Health [Bethesda]
5 AbScent
6 Penn State - Pennsylvania State University
7 Yale University [New Haven]
8 University of Tennessee
9 University of Illinois at Urbana-Champaign [Urbana]
10 ICN - Institut de Chimie de Nice
11 Buenos Aires University and GEOG (Grupo de Estudio de Olfato y Gusto)
12 CAGT - Centre d'anthropologie et de génomique de Toulouse
13 UNIBA - Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro
14 UC - University of California
15 Utrecht University [Utrecht]
16 TUM - Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne]
17 Monell Chemical Senses Center
18 Regional Hospital West Jutland [Denmark]
19 Helsingin yliopisto = Helsingfors universitet = University of Helsinki
20 UiO - University of Oslo
21 Karunya Institute of Technology and Sciences
22 Tata Institute of Fundamental Research [Bangalore]
23 Sidra Medicine [Doha, Qatar]
24 IIIT-Delhi - Indraprastha Institute of Information Technology [New Delhi]
25 SQU - Sultan Qaboos University
26 SDSU - San Diego State University
27 Goethe-University Frankfurt am Main
28 State University of Londrina = Universidade Estadual de Londrina
29 Elena Cantone
30 University of Queensland - The Diamantina Institute
31 University of Queensland [Brisbane]
32 UniFI - Università degli Studi di Firenze = University of Florence
33 UCL - University College of London [London]
34 UC San Diego Health
35 Karl-Franzens-Universität Graz
36 Howard University College of Medicine [Washington, DC, USA]
37 Geneva University Hospitals and Geneva University
38 Cliniques Universitaires Saint-Luc [Bruxelles]
39 Aristotle University of Thessaloniki
40 SISSA / ISAS - Scuola Internazionale Superiore di Studi Avanzati / International School for Advanced Studies
41 Stockholm University
42 UEA - University of East Anglia [Norwich]
43 Towson University [Towson, MD, United States]
44 A.N. Severtsov Institute of Ecology and Evolution
45 Unipd - Università degli Studi di Padova = University of Padua
46 Biruni University
47 CRNL - Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center
48 Public Hospital Barrio Obrero - Hospital General de Barrio Obrero [Asunción, Paraguay]
49 Private practice [Milan]
50 DreamAir Llc
51 OSU - Oregon State University
52 Karolinska Institutet [Stockholm]
53 Uninsubria - Universitá degli Studi dell’Insubria = University of Insubria [Varese]
54 IBM Watson Research Center
55 Navarrabiomed-IdiSNA
56 UEX - Universidad de Extremadura - University of Extremadura
57 TU Dresden - Technische Universität Dresden = Dresden University of Technology
58 HUJ - The Hebrew University of Jerusalem
59 UF - University of Florida [Gainesville]
60 Temple University [Philadelphia]
61 WUR - Wageningen University and Research [Wageningen]
62 Radboud University [Nijmegen]
63 FAU - Friedrich-Alexander Universität Erlangen-Nürnberg
64 UCHILE - Universidad de Chile = University of Chile [Santiago]
65 FUTA - Federal University of Technology of Akure
66 UC Berkeley - University of California [Berkeley]
67 CSGA - Centre des Sciences du Goût et de l'Alimentation [Dijon]
68 UBFC - Université Bourgogne Franche-Comté [COMUE]
69 University of Dayton
70 IUMS - Iran University of Medical Sciences [Tehran, Iran]
71 "Federico II" University of Naples Medical School
72 UNIVR - Università degli studi di Verona = University of Verona
73 Xjtu - Xi'an Jiaotong University
74 IRTA - Institute of Agrifood Research and Technology
75 UAF - University of Alaska [Fairbanks]
76 The Hebrew University Medical Center
77 UMASS - University of Massachusetts System
78 Instituto Universitario del Hospital Italiano [Buenos Aires, Argentina]
79 Johns Hopkins University School of Medicine [Baltimore]
80 IPM - Institute for Research in Fundamental Sciences [Tehran]
81 CSIRO - CSIRO Agriculture and Food
82 GMU - The First Affiliated Hospital of Guangzhou Medical University
83 UCD - University College Dublin [Dublin]
84 UQTR - Université du Québec à Trois-Rivières
85 Guy’s and St. Thomas’ Hospitals
86 Kilis Yedi Aralik University
87 University of Otago [Dunedin, Nouvelle-Zélande]
88 Sancaktepe Education and Research Hospital
89 University of Pennsylvania [Philadelphia]
90 UC San Diego - University of California [San Diego]
91 Tata Institute of Fundamental Research
92 Indiana University [Bloomington]
93 CUMC - Columbia University Medical Center
94 University of Edinburgh
95 UC Merced - University of California [Merced]
96 University of Stirling
97 University of London [London]
98 FSU - Florida State University [Tallahassee]
99 Université catholique de Bukavu
100 USQ - University of Southern Queensland

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.

Keywords: anosmia; chemosensory; coronavirus; hyposmia; olfactory; prediction

Domains: Life Sciences [q-bio]; Neurons and Cognition [q-bio.NC]; Life Sciences [q-bio]; Human health and pathology; Life Sciences [q-bio]; Life Sciences [q-bio]; Human health and pathology; Sensory Organs; Life Sciences [q-bio]; Human health and pathology; Infectious diseases

Richard C. Gerkin, Kathrin Ohla, Maria G. Veldhuizen, Paule V. Joseph, Christine E. Kelly, et al.. Recent smell loss is the best predictor of COVID-19 among individuals with recent respiratory symptoms. Chemical Senses, 2021, 46, pp.bjaa081. ⟨10.1093/chemse/bjaa081⟩. ⟨hal-03367315⟩