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Chemosensory Losses in Active Probable Delta and Omicron Variants Breakthrough COVID-19 Cases
Kym Man1, Aayah Mohamed-Osman2, Kai Zhao2, Susan P. Travers3, Christopher T. Simons1
1Department of Food Science and Technology, Columbus, OH, USA, 2Department of Otolaryngology, Columbus, OH, USA, 3Division of Biosciences, Columbus, OH, USA
Chemosensory loss is a COVID-19 hallmark but it is unclear if the Delta (DL) and Omicron (OM) variants similarly impact smell and taste function, and whether vaccination results in less severe symptoms. 80 subjects with prior confirmed/clinical probable diagnosis of COVID-19 and 125 controls performed sensory tests via Zoom using the NIH toolbox 9-item scratch and sniff odor id test and bitter intensity ratings of 1mM quinine. 39 subjects had active COVID-19 (symptom onset <14d) at the time of testing, and most (36/39) were vaccinated. 25 of these active cases were likely infected by the DL variant with the rest as probable OM cases based on diagnosis dates. The other 41 positive cases occurred prior to the DL surge in the US with diagnosis >14d prior to sensory testing (x=6.5m). 9 of the 41 subjects reported smell loss (8 long-haulers); objective testing confirmed smell loss comparable to the active cohort in 7 (78%). 16 of the remaining 32 (50%) without reported smell loss still had objective losses. All probable DL-variant cases (100%) had objective smell loss based on age and gender adjusted normative cutoffs, although only 16/25 reported smell/taste loss. None of the likely OM cases reported smell/taste loss, yet 5/11 (45%) subjects had objective smell loss, higher than in controls (34%). For taste function, while COVID+ subjects with self-reported chemosensory loss rated quinine as less bitter, the difference was not significant (p>0.05). The results demonstrate (1) the DL variant may cause similar if not more severe impact on olfactory function while the impact of the OM variant is less profound and (2) vaccination does not fully prevent chemosensory loss. Results also add to evidence that self-reported chemosensory loss is useful but may not capture the full spectrum of losses from COVID-19.
Transient Changes In Oral Chemesthesis, Taste And Smell In COVID-19 - Longitudinally Intensive Data From A Small Case-Control Series
John E Hayes1,2, Elisabeth M Weir1,2, Richard C Gerkin3, Steven D Munger4,5, Cara L Exten6
1Sensory Evaluation Center, College of Agricultural Sciences, University Park, PA, USA, 2Department of Food Science, College of Agricultural Sciences, University Park, PA, USA, 3School of Life Sciences, Arizona State University, Tempe, AZ, USA, 4Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville , FL, USA, 5Center for Smell and Taste, University of Florida, Gainesville, FL, USA, 6Ross and Carol Nese College of Nursing, The Pennsylvania State University, University Park, PA, USA
Anosmia is common with influenza or rhinovirus infections, but loss of taste or chemesthesis is rare. Reports of true taste loss with COVID19 were viewed skeptically until confirmed by multiple studies. Nasal menthol thresholds may be elevated in some with prior COVID19, but data on oral chemesthesis are lacking. Many patients recover quickly, but precise timing and synchrony of recovery are unclear. We collected broad sensory measures over 28 days, recruiting adults (18-45 yrs) who were COVID19 positive or recently exposed (close contacts per CDC criteria). Participants received nose clips, red jellybeans (Sour Cherry, Cinnamon) and scratch-n-sniff cards (ScentCheckPro). To assess changes during disease onset, we identified 4 cases enrolled before Day 1 of illness; 4 controls (close contacts who never developed COVID) were matched via age, sex and race. Variables included sourness and sweetness (Sour Cherry jellybeans), oral burn (Cinnamon jellybeans), mean orthonasal intensity of 4 odors (ScentCheckPro), and perceived nasal blockage. Data were plotted over 28 days, creating panel plots for each case and control. Controls exhibited stable ratings over time, in contrast to COVID-19 cases, who showed sharp deviations over time. No single pattern of taste loss or recovery was apparent, implying different taste qualities may recover at different rates. Oral burn was transiently reduced for some before recovering quickly, implying acute loss may be missed in data collected post-infection. Major deviations in odor intensity were unexplained by nasal blockage. Collectively, daily testing shows orthonasal smell, oral chemesthesis and taste are all altered by COVID19, and such disruption is dyssynchronous for different chemical senses, with variable loss and recovery rates across modalities and individuals.
Prevalence of Smell and Taste Loss in Youth with COVID-19
Evan A. Guerra1, Vicente Ramirez2, Stephanie Hunter1, Danielle R. Reed1, Pamela H. Dalton1, Valentina Parma1
1Monell Chemical Senses Center, Philadelphia, PA, USA, 2UC Merced, Merced, CA, USA
Chemosensory dysfunction is a common and early symptom of COVID-19, even in otherwise asymptomatic patients. In COVID-19-positive adults, the prevalence of smell loss is ~67% and of taste loss is ~42%. Despite the promise of tracking smell and taste as a discriminatory symptom of COVID-19, there has been little effort to quantify the prevalence of these symptoms in youth. Here we aim to examine the extent to which smell and taste have been assessed among youth with active COVID-19. To date, only 4.7% (N = 39/826) of studies including COVID-19 positive youth assessed smell and/or taste loss. We use random-effects meta-analysis to pool 39 studies including individuals younger than 18 years old, with confirmed or suspected COVID-19 diagnosis in which a measure of smell and/or taste was reported (24 secondary reports from medical records or parental reports, 13 self reports, 2 direct testing) and estimate the effect of chemosensory dysfunction due to COVID-19 in youth (age 0-17 years, 11 months, 29 days). Based on self-reports alone, the prevalence of smell loss is 14% (vs. 8% secondary reports) and the prevalence of taste loss is 18% (vs. 7% secondary reports). The only paper using a standardized direct test for smell loss (an adult version of the Sniffin' Sticks odor identification test) indicates a much higher prevalence of smell loss of 86% (N = 79). Prevalence increases from age 10, but no sex differences are revealed. We highlight the need for guidelines to assess chemosensory loss in children with suspected COVID-19. At a minimum, we recommend the use of self-reports to document the prevalence of chemosensory loss due to iCOVID-19 in youth, and possibly mitigate the burden of the COVID-19 pandemic in this age category.
Symptoms of Depression Change with Olfactory Function
Agnieszka Sabiniewicz1,2, Leonie Hoffman1, Antje Haehner1, Thomas Hummel1
1Interdisciplinary Center, Smell & Taste,Dresden,Germany, 2Institute of Psychology, Wrocław,Poland
Olfactory loss is associated with symptoms of depression. The present study, conducted on a large cohort of mostly dysosmic patients, aimed to investigate whether improvement in olfactory performance would correspond with a decrease in depression severity. In 171 participants, we assessed olfactory function and severity of depression before and after an average interval of 11 months, with many patients showing improvement. Separate analyses were conducted for a) the whole group of patients and b) the group of dysosmic patients using both classic and Bayesian approaches. Student t-test demonstrated that the whole sample improved consistently, especially within the group of dysosmic patients in terms of odor identification. The dysosmic group also improved in odor threshold and overall olfactory function. Pearson correlation showed that increase in olfactory function corresponded with decrease in depression severity, particularly in dysosmic patients. To conclude, the present results indicate that symptoms of depression change with olfactory function in general and odor identification in particular.
Well-being in patients with olfactory dysfunction
Yiling Mai, Susanne Menzel , Mandy Cuevas, Antje Hähner, Thomas Hummel
Smell and Taste Clinic, Department of Otorhinolaryngology, Technische Universität Dresden, Dresden, Germany
This cross-sectional, retrospective study aimed to investigate the differences in well-being (WB) among patients with olfactory disorder (OD) with quantitative and/or qualitative olfactory dysfunctions, and to identify factors associated with WB. We included 470 OD patients. WB (WHO-5 questionnaire), quantitative olfactory function (Sniffin Sticks) and qualitative dysfunction were assessed. Based on normative data, 44% of patients with anosmia, 31% with hyposmia, 36% with parosmia and 41% with phantosmia had poor WB, while the remainder showed good well-being. For quantitative function, anosmia patients showed lower WB scores than hyposmia and normosmia patients (all p's<0.03). For qualitative dysfunction, patients with severe parosmia showed lower WB scores than patients without and with less severe parosmia (p's<0.01). Regarding OD causes in hyposmic patients, post-viral patients showed poorer WB than idiopathic patients (p=0.01); sinonasal patients had lower WB than post-traumatic and idiopathic patients (all p's<0.04). The WB score positively correlated weakly, but significantly with the Threshold test score (r=0.11, p=0.02), and negatively with severity of parosmia (r=-0.10, p=0.03). Hierarchical regression analyses showed that sex, T and TDI scores significantly predicted WB score in OD patients. Our results implied that quantitative and qualitative dysfunction is associated with WB. However, only patients with severe dysfunction showed significantly lower WB. And for those with severe dysfunction, some of these patients indicated good WB. While this needs to be better understood, in order to improve WB, in these patients it appears to be highly important to improve olfactory function, and here especially olfactory sensitivity. Key words: anosmia, parosmia, well-being, olfactory dysfunction.
Binge eating suppresses flavor representations in the mouse olfactory cortex
Hung Lo1,2, Anke Schönherr1, Malinda L.S. Tantirigama3,5, Robert Sachdev3, Katharina Stumpenhorst4, Marion Rivalan4,5, York Winter4,5, Dietmar Schmitz1,2,5,6, Friedrich Johenning1,2
1Neuroscience Research Center, Charité-Universitätsmedizin Berlin, Berlin,Germany, 2Einstein Center for Neurosciences Berlin, Berlin, Germany, 3Institut für Biologie, Humboldt Universität zu Berlin, Berlin, Germany, 4Cognitive Neurobiology, Humboldt Universität zu Berlin, Berlin, Germany, 5Cluster of Excellence NeuroCure, Berlin, Germany, 6Center for Neurodegenerative Diseases (DZNE), Berlin, Germany
Appropriate feeding behavior is the foundation of maintaining homeostasis. Elevated feeding speed (binge eating) is a common trait of eating disorders and is associated with obesity. It is also known that flavor perception has an active role in regulating feeding. However, the effects of feeding speed on flavor sensory feedback remain unknown. By using miniscope in mice, we show that binge eating suppresses neuronal activity in the anterior olfactory (piriform) cortex (aPC). This binge-induced suppression is due to local GABAergic interneurons in aPC, but not due to degraded odor inputs from the olfactory bulb. We further excluded the inhibitory effect from serotonergic modulation in aPC by using in vivo serotonin imaging. Taken together, our results provide clear circuit mechanisms of binge-induced flavor modulation, which may explain binge-induced overeating due to suppression of sensory feedback of food items.
A Persistent Behavioural State Enables Sustained Predation of Humans by Mosquitoes
Trevor Sorrells, Anjali Pandey, Adriana Rosas, Leslie Vosshall
Rockefeller University, New York, NY, USA
Predatory animals pursue prey in a noisy sensory landscape, deciding when to continue or abandon their chase. The mosquito Aedes aegypti is a micropredator that first detects humans at a distance through sensory cues such as carbon dioxide. As a mosquito nears its target it senses more proximal cues such as body heat that guides it to a meal of blood. How long the search for blood continues after initial detection of a human is not known. Here we show that a 5-second optogenetic pulse of fictive carbon dioxide induced a persistent behavioural state in female mosquitoes that lasted for more than 10 minutes. This state is highly specific to females searching for a blood meal and was not induced in recently blood-fed females or in males, who do not feed on blood. In males that lack the gene fruitless, which controls persistent social behaviours in other insects, fictive carbon dioxide induced a long-lasting behaviour response resembling the predatory state of females. Finally, we show that the persistent state triggered by detection of fictive carbon dioxide enabled females to engorge on a blood meal mimic offered up to 14 minutes after the initial 5-second stimulus. Our results demonstrate that a persistent internal state allows female mosquitoes to integrate multiple human sensory cues over long timescales, an ability that is key to their success as an apex micropredator of humans.
Micellar casein from milk reduces the oral burn from capsaicin in a dose dependent manner
Brigitte A. Farah1,2, John N. Coupland2, John E. Hayes1,2
1Sensory Evaluation Center, University Park, PA, USA, 2Department of Food Science, College of Agricultural Sciences, The Pennsylvania State University , University Park, PA, USA
The hydrophobic chemical capsaicin from chili peppers causes oral burning in the mouth via activation of the TRPV1 receptor. Folk wisdom and psychophysical experiments each suggest fluid milk is the best means to reduce burn after consumption, but specific mechanism(s) remain unknown. It is widely assumed this reduction arises from partitioning of the hydrophobic agonist away from the receptor into the lipid phase, but data from Nolden et al. show full fat milk is no better than skim milk at reducing the burn, leading to speculation this may be due to sequestration by milk protein rather than hydrophobicity. Here, we selected micellar casein (a phosphoprotein that makes up the bulk of protein in milk) as a model protein and tested its ability to (a) bind with capsaicin in vitro, and (b) reduce oral burn in a convenience sample of untrained moderate chili consumers. In vitro, micellar casein is capable of binding capsaicin in a dose dependent manner. In vivo, 92 adults rated the burn of 4 stimuli for 120 seconds each using discrete interval time intensity scaling on a general Labelled Magnitude Scale, with appropriate breaks between stimuli. The four stimuli contained: no protein (0% casein / 5 ppm capsaicin), low protein (2% / 5 ppm), high protein (5% / 5 ppm), and vehicle only (5% / 0 ppm). Burn ratings for all samples with capsaicin peaked at 10 sec before decaying over 2 min; burn of the protein only vehicle was below weak on all trials. As hypothesized, the no protein stimulus had the greatest peak burn (near moderate), while peak burn for the low protein and high protein stimuli were reduced by ~21% and ~42%, respectively. Further studies with whey protein are underway. Collectively, these data support the hypothesis that micellar casein reduces oral burn and this may be due to protein binding.
