Recent smell loss is the best predictor of COVID-19: a preregistered, cross-sectional study

Gerkin, R. C.; Ohla, K.; Veldhuizen, M. G.; Joseph, P. V.; Kelly, C. E.; Bakke, A. J.; Steele, K. E.; Farruggia, M. C.; Pellegrino, R.; Pepino, M. Y.; Bouysset, C.; Soler, G. M.; Pereda-Loth, V.; Dibattista, M.; Cooper, K. W.; Croijmans, I.; Di Pizio, A.; Ozdener, M. H.; Fjaeldstad, A. W.; Lin, C.; Sandell, M. A.; Singh, P. B.; Brindha, V. E.; Olsson, S. B.; Saraiva, L. R.; Ahuja, G.; Alwashahi, M. K.; Bhutani, S.; D'Errico, A.; Fornazieri, M. A.; Golebiowski, J.; Hwang, L.-D.; Öztürk, L.; Roura, E.; Spinelli, S.; Whitcroft, K. L.; Faraji, F.; Fischmeister, F. P. S.; Heinbockel, T.; Hsieh, J

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