Recent Smell Loss Is the Best Predictor of COVID-19 Among Individuals With Recent Respiratory Symptoms.

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.

More Than Smell-COVID-19 Is Associated With Severe Impairment of Smell, Taste, and Chemesthesis.

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 multilingual, international questionnaire to assess self-reported quantity and quality of perception in 3 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, and 8 others, aged 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 ± standard deviation), 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 the lack of perceived nasal obstruction suggest that severe acute respiratory syndrome coronavirus strain 2 (SARS-CoV-2) infection may disrupt sensory-neural mechanisms.

Non-invasive vagus nerve stimulation in a hungry state decreases heart rate variability.

Vagus nerve signals from the gut to brain carry information about nutrients and drive food reward. Such signals are disrupted by consuming large amounts of high-calorie foods, necessitating greater food intake to elicit a similar neural response. Non-invasive vagus nerve stimulation (nVNS) via a branch innervating the ear is a candidate treatment for obesity in humans. There is disagreement on the optimal location of nVNS in the ear for experimental and clinical studies. There are also no studies comparing nVNS in hungry and post-prandial states. We aimed to compare ear position(s) for nVNS and explore the effects of nVNS during hungry and post-prandial states on proxies for autonomic outflow (heart-rate variability) and efferent metabolism (gastric wave frequency and resting energy expenditure). In a within-subject design, 14 participants (10 women, on average 29.4 +/- 6.7 years old) received nVNS in four different locations (cymba conchae, tragus, earlobe, or tragus AND cymba conchae) on separate days. In each session, participants were asked to consume a palatable chocolate flavored milk. With electrography on the abdomen and indirect calorimetry in a canopy, we measured electro-cardiogram, electro-gastrogram and resting energy expenditure for 15 min before and at least 35 min after consumption of the palatable drink. We also collected ratings of the palatable drink and internal and other states. Pre-drink consumption (in a hungry state) we observed no differences in the effect of location of acute nVNS on resting energy expenditure and gastric wave measures. However, nVNS in cymba conchae decreases heart-rate variability (relative to sham) and ratings of how much participants want to consume the drink (relative to tragus AND cymba conchae and a trend relative to sham). After drink consumption and with continued nVNS, gastric wave frequency is unchanged, and resting energy expenditure increases regardless of stimulation location. Heart-rate variability decreases in all locations, except cymba conchae. We also observe a trend for an increase in gastric wave amplitude in late post-drink consumption time-points in cymba conchae. We observe no support for the combined stimulation of tragus AND cymba conchae being more effective than either of the individual locations. These results suggest that nVNS in the cymba conchae in a hungry state has a similar acute effect on vagal tone as food consumption: to decrease heart rate variability. This effect then negates the usual postprandial effects of a decrease in heart rate variability as seen in the other nVNS locations. These preliminary observations suggest that nVNS in cymba conchae may act primarily on vagal afferent autonomic (and only modestly on metabolic output) in a similar way as food consumption does.

tVNS Increases Liking of Orally Sampled Low-Fat Foods: A Pilot Study.

Recently a role for the vagus nerve in conditioning food preferences was established in rodents. In a prospective controlled clinical trial in humans, invasive vagus nerve stimulation shifted food choice toward lower fat content. Here we explored whether hedonic aspects of an orally sampled food stimulus can be modulated by non-invasive transcutaneous vagus nerve stimulation (tVNS) in humans. In healthy participants (n = 10, five women, 20-32 years old, no obesity) we tested liking and wanting ratings of food samples with varying fat or sugar content with or without tVNS in a sham-controlled within-participants design. To determine effects of tVNS on food intake, we also measured voluntary consumption of milkshake. Spontaneous eye blink rate was measured as a proxy for dopamine tone. Liking of low-fat, but not high-fat puddings, was higher for tVNS relative to sham stimulation. Other outcomes showed no differences. These findings support a role for the vagus nerve promoting post-ingestive reward signals. Our results suggest that tVNS may be used to increase liking of low-calorie foods, which may support healthier food choices.

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

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