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
Subject(s)
COVID-19 , Fever , Olfaction Disorders , CoughABSTRACT
Among the prominent clinical symptoms such as fatigue, shortness of breath, fever, and cough, 2019-nCoV infected individuals often experience hyposmia/anosmia (decrease or loss of sense of smell). Angiotensin I Converting Enzyme 2 (ACE2), a key host receptor has now been established as an important moiety for the entry of 2019-nCoV into the host cells. A multitude of studies estimated the expression of ACE2 in multiple organs including heart, kidney, intestines, lungs, buccal cavity, etc. The ongoing medical examinations and the autopsy reports of the diseased individuals strongly corroborate these organ/tissue-level molecular insights. Olfactory mucosa harbors multiple functionally distinct cell types. Zeroing in on the cell lineages that underpin infection associated loss of olfaction may provide new leads for diagnostics/clinical management of 2019-nCoV infected individuals. Our pointed bioinformatic analysis of single-cell expression profiles underscored selective expression of ACE2 in a subset of horizontal basal cells (HBCs) and sustentacular cells (SUSs) of the olfactory mucosa in humans. Inspection of the ACE2 levels in the olfactory mucosa of 4 additional mammalian species revealed comparable expression patterns, indicating the risk of olfactory dysfunction in these species. In summary, our findings pinpoint the molecular rationale of loss of smell in 2019-nCoV infected patients.