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.

Over the last two decades, neuroimaging methods have identified a variety of taste-responsive brain regions. Their precise location, however, remains in dispute. For example, taste stimulation activates areas throughout the insula and overlying operculum, but identification of subregions has been inconsistent. Furthermore, literature reviews and summaries of gustatory brain activations tend to reiterate rather than resolve this ambiguity. Here we used a new meta-analytic method [activation likelihood estimation (ALE)] to obtain a probability map of the location of gustatory brain activation across fourteen studies. The map of activation likelihood values can also serve as a source of independent coordinates for future region-of-interest analyses. We observed significant cortical activation probabilities in: bilateral anterior insula and overlying frontal operculum, bilateral mid dorsal insula and overlying Rolandic operculum, and bilateral posterior insula/parietal operculum/postcentral gyrus, left lateral orbitofrontal cortex (OFC), right medial OFC, pregenual anterior cingulate cortex (prACC) and right mediodorsal thalamus. This analysis confirms the involvement of multiple cortical areas within insula and overlying operculum in gustatory processing and provides a functional “taste map” which can be used as an inclusive mask in the data analyses of future studies. In light of this new analysis, we discuss human central processing of gustatory stimuli and identify topics where increased research effort is warranted.

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Although stress is an increasing global health problem in cities, urban green spaces can provide health benefits. There is, however, a lack of understanding of the link between physiological mechanisms and qualities of urban green spaces. Here, we compare the effects of visual stimuli (360 degree virtual photos of an urban environment, forest, and park) to the effects of congruent olfactory stimuli (nature and city odours) and auditory stimuli (bird songs and noise) on physiological stress recovery. Participants (N = 154) were pseudo-randomised into participating in one of the three environments and subsequently exposed to stress (operationalised by skin conductance levels). The park and forest, but not the urban area, provided significant stress reduction. High pleasantness ratings of the environment were linked to low physiological stress responses for olfactory and to some extent for auditory, but not for visual stimuli. This result indicates that olfactory stimuli may be better at facilitating stress reduction than visual stimuli. Currently, urban planners prioritise visual stimuli when planning open green spaces, but urban planners should also consider multisensory qualities.

Our knowledge regarding the neural processing of the three chemical senses has been lagging behind that of our other senses considerably. It is only during the last 25 years that significant advances have been made in our understanding of where in the human brain odors, tastants, and trigeminal stimuli are processed. Here we provide an overview of the current knowledge of how the human brain processes chemical stimuli based on findings in neuroimaging studies using positron emission tomography and functional magnetic resonance imaging. Additionally, we provide new insights from recent meta-analyses, based on all published neuroimaging studies of the chemical senses, of where the chemical senses converge in the brain.

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.

The rapid demographical shift occurring in our society implies that understanding of healthy aging and age-related diseases is one of our major future challenges. Sensory impairments have an enormous impact on our lives and are closely linked to cognitive functioning. Due to the inherent complexity of sensory perceptions, we are commonly presented with a complex multisensory stimulation and the brain integrates the information from the individual sensory channels into a unique and holistic percept. The cerebral processes involved are essential for our perception of sensory stimuli and becomes especially important during the perception of emotional content. Despite ongoing deterioration of the individual sensory systems during aging, there is evidence for an increase in, or maintenance of, multisensory integration processing in aging individuals. Within this comprehensive literature review on multisensory integration we aim to highlight basic mechanisms and potential compensatory strategies the human brain utilizes to help maintain multisensory integration capabilities during healthy aging to facilitate a broader understanding of age-related pathological conditions. Further our goal was to identify where further research is needed.

Observational studies have suggested that with time, some diseases result in a characteristic odor emanating from different sources on the body of a sick individual. Evolutionarily, however, it would be more advantageous if the innate immune response were detectable by healthy individuals as a first line of defense against infection by various pathogens, to optimize avoidance of contagion. We activated the innate immune system in healthy individuals by injecting them with endotoxin (lipopolysaccharide). Within just a few hours, endotoxin-exposed individuals had a more aversive body odor relative to when they were exposed to a placebo. Moreover, this effect was statistically mediated by the individuals' level of immune activation. This chemosensory detection of the early innate immune response in humans represents the first experimental evidence that disease smells and supports the notion of a "behavioral immune response" that protects healthy individuals from sick ones by altering patterns of interpersonal contact.