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, and generally lacked quantitative measurements. 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.

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.

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Background: Clinical diagnosis of COVID-19 poses an enormous challenge to early detection and prevention of COVID-19, which is of crucial importance for pandemic containment. Cases of COVID-19 may be hard to distinguish clinically from other acute viral diseases, resulting in an overwhelming load of laboratory screening. Sudden onset of taste and smell loss emerge as hallmark of COVID-19. The optimal ways for including these symptoms in the screening of suspected COVID-19 patients should now be established. Methods: We performed a case-control study on patients that were PCR-tested for COVID-19 (112 positive and 112 negative participants), recruited during the first wave (March 2020 - May 2020) of COVID-19 pandemic in Israel. Patients were interviewed by phone regarding their symptoms and medical history and were asked to rate their olfactory and gustatory ability before and during their illness on a 1-10 scale. Prevalence and degrees of symptoms were calculated, and odds ratios were estimated. Symptoms-based logistic-regression classifiers were constructed and evaluated on a hold-out set. Results: Changes in smell and taste occurred in 68% (95% CI 60%-76%) and 72% (64%-80%), of positive patients, with 24 (11-53 range) and 12 (6-23) respective odds ratios. The ability to smell was decreased by 0.5 ± 1.5 in negatives, and by 4.5 ± 3.6 in positives, and to taste by 0.4 ± 1.5 and 4.9 ± 3.8, respectively (mean ± SD). A penalized logistic regression classifier based on 5 symptoms (degree of smell change, muscle ache, lack of appetite, fever, and a negatively contributing sore throat), has 66% sensitivity, 97% specificity and an area under the ROC curve of 0.83 (AUC) on a hold-out set. A classifier based on degree of smell change only is almost as good, with 66% sensitivity, 97% specificity and 0.81 AUC. Under the assumption of 8% positives among those tested, the predictive positive value (PPV) of this classifier is 0.68 and negative predictive value (NPV) is 0.97. Conclusions: Self-reported quantitative olfactory changes, either alone or combined with other symptoms, provide a specific and powerful tool for clinical diagnosis of COVID-19. The applicability of this tool for prioritizing COVID-19 laboratory testing is facilitated by a simple calculator presented here.

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.