Identification of the needs of individuals affected by COVID-19.

BACKGROUND: The optimal management of COVID-19 symptoms and their sequelae remains an important area of clinical research. Policy makers have little scientific data regarding the effects on the daily life of affected individuals and the identification of their needs. Such data are needed to inform effective care policy. METHODS: We studied 639 people with COVID-19 resident in France via an online questionnaire. They reported their symptoms, effects on daily life, and resulting needs, with particular focus on olfaction. RESULTS: The results indicate that a majority of participants viewed their symptoms as disabling, with symptoms affecting their physical and mental health, social and professional lives. 60% of the individuals reported having unmet medical, psychological and socio-professional support needs. Finally, affected individuals were concerned about the risk and invasiveness of possible treatments as shown by a preference for non-invasive intervention over surgery to cure anosmia. CONCLUSIONS: It is important that policy makers take these needs into consideration in order to assist affected individuals to regain a normal quality of life.

The impact of COVID-19 has been substantial, both on individuals' health and on society. Information is needed to understand the biological mechanisms underlying the illness and to provide appropriate support for people affected. This study uses data from an online questionnaire of adults diagnosed with COVID-19 to characterize symptoms, understand their impact on peoples' everyday lives, and determine the support that people need. Our over-arching analysis of symptoms experienced reveals that heart- and skin-related symptoms are linked to chronic illness, and symptoms related to the sense of smell may have a different underlying disease mechanism. Most respondents had a mild initial illness, but their symptoms were long-lasting and had a severe impact. Our findings show that sufferers need different kinds of support in order to regain a normal quality of life.

Influence of the human body odor compound HMHA on face perception.

Body odors convey information about the individuals, but the mechanisms are not fully understood yet. As far as human reproduction is concerned, molecules that are produced in sexually dimorphic amounts could be possible chemosignals. 3-hydroxy-3-methylhexanoic acid (HMHA) is one of them-more typical of men. Here, we investigated the possibility that the perception of gender and attractiveness in human faces could be implicitly influenced by this compound. Clearly feminine, ambiguous and clearly masculine faces were primed with an odor of HMHA, a control odor or air. Based on 100-ms face presentation, 40 raters had to identify the face's gender as quickly as possible and provide attractiveness evaluations. 3-hydroxy-3-methylhexanoic acid tended to be perceived as less pleasant and induced lower sniff duration in women compared with men. As to the effects of HMHA on face perception (vs. control conditions), we found that gender identification and the associated response time were unaffected by HMHA. Attractiveness of the faces, however, increased in presence of HMHA, but not in a sex-specific manner and only for unattractive faces with ambiguous gender. In sum, this study found no evidence in favor of a possible role of this sexually dimorphic compound in intrasexual competition nor in intersexual attraction.

Past, Present, and Future of Human Chemical Communication Research.

Although chemical signaling is an essential mode of communication in most vertebrates, it has long been viewed as having negligible effects in humans. However, a growing body of evidence shows that the sense of smell affects human behavior in social contexts ranging from affiliation and parenting to disease avoidance and social threat. This article aims to (a) introduce research on human chemical communication in the historical context of the behavioral sciences; (b) provide a balanced overview of recent advances that describe individual differences in the emission of semiochemicals and the neural mechanisms underpinning their perception, that together demonstrate communicative function; and (c) propose directions for future research toward unraveling the molecular principles involved and understanding the variability in the generation, transmission, and reception of chemical signals in increasingly ecologically valid conditions. Achieving these goals will enable us to address some important societal challenges but are within reach only with the aid of genuinely interdisciplinary approaches.

Investigating the human chemical communication of positive emotions using a virtual reality-based mood induction.

Humans can communicate their emotions to others via volatile emissions from their bodies. Although there is now solid evidence for human chemical communication of fear, stress and anxiety, investigations of positive emotions remain scarce. In a recent study, we found that women's heart rate and performance in creativity tasks were modulated by body odors of men sampled while they were in a positive vs. neutral mood. However, inducing positive emotions in laboratory settings remains challenging. Therefore, an important step to further investigate the human chemical communication of positive emotions is to develop new methods to induce positive moods. Here, we present a new mood induction procedure (MIP) based on virtual reality (VR), that we assumed to be more powerful than videos (used in our previous study) to induce positive emotions. We hypothesized that, consequently, given the more intense emotions created, this VR-based MIP would induce larger differences between the receivers' responses to the positive body odor versus a neutral control body odor, than the Video-based MIP. The results confirmed the higher efficacy of VR to induce positive emotions compared with videos. More specifically, VR had more repeatable effects between individuals. Although positive body odors had similar effects to those found in the previous video study, especially faster problem solving, these effects did not reach statistical significance. These outcomes are discussed as a function of the specificities of VR and of other methodological parameters, that may have prevented the observation of such subtle effects and that should be understood more in-depth for future studies on human chemical communication.

Phantom smells: a prevalent COVID-19 symptom that progressively sets in.

PURPOSE: One of the long-term symptoms of COVID-19 is phantosmia, a type of Olfactory Disorder (OD) that has deleterious impacts on patients' quality of life. The aim of this article was to study how this poorly understood qualitative OD manifests itself in the COVID-19. METHODS: 4691 patients with COVID-19 responded to our online questionnaire focusing on COVID-19-related OD. We first analyzed the prevalence of phantosmia in this population. Then, with the help of Natural Language Processing techniques, we investigated the qualitative descriptions of phantom smells by the 1723 respondents who reported phantosmia. RESULTS: The prevalence of phantosmia was of 37%. Women were more likely to report phantosmia than men, as well as respondents for whom OD was described as fluctuating rather than permanent, lasted longer, was partial rather than total and appeared progressively rather than suddenly. The relationship between OD duration and phantosmia followed a logarithmic function, with a prevalence of phantosmia increasing strongly during the first 2 months of the disease before reaching a plateau and no decrease over the 15 months considered in this study. Qualitative analyses of phantosmia descriptions with a sentiment analysis revealed that the descriptions were negatively valenced for 78% of the respondents. Reference to "tobacco" was more frequent in non-smokers. Source names and odor characteristics were used differently according to age and OD duration. CONCLUSION: The results of this descriptive study of phantosmia contribute to the current efforts of the medical community to better understand and treat this rapidly increasing COVID-19-related OD.

Systematic MRI in persistent post-Covid-19 olfactory dysfunction should be reassessed.

BACKGROUND: Magnetic resonance imaging (MRI) is the gold standard in the etiological assessment of a persistent olfactory dysfunction (OD). While the utility of imaging in COVID-19-related OD has yet to be established, MRI is recommended in all patients with persistent OD. The high prevalence of the latter after SARS-CoV-2 infection means evaluating this strategy is an important public health matter. METHODS: The main objective was to examine the impact of systematic MRI on the management of patients with OD. All adult patients consulting for persistent OD (>2 months) after primary SARS-COV-2 infection (PCR) between March 2020 and December 2021 were included (n = 67). The secondary objective was to evaluate the relationship between the severity of the OD as measured by psychophysical testing (ETOC) and the volume of the olfactory bulb (OB) measured by MRI. RESULTS: All patients underwent MRI, and none led to a change in diagnosis or treatment. Among them, 82% (55/67) were considered normal by the radiologist on initial interpretation. There were no significant differences (visual analysis or OB volume) between groups (mild, moderate, and severe hyposmia). CONCLUSION: Systematic MRI may be unnecessary in patients whose persistent OD began soon (a few days) after confirmed SARS-CoV-2 infection.

An olfactory self-test effectively screens for COVID-19.

Background: Key to curtailing the COVID-19 pandemic are wide-scale screening strategies. An ideal screen is one that would not rely on transporting, distributing, and collecting physical specimens. Given the olfactory impairment associated with COVID-19, we developed a perceptual measure of olfaction that relies on smelling household odorants and rating them online. Methods: Each participant was instructed to select 5 household items, and rate their perceived odor pleasantness and intensity using an online visual analogue scale. We used this data to assign an olfactory perceptual fingerprint, a value that reflects the perceived difference between odorants. We tested the performance of this real-time tool in a total of 13,484 participants (462 COVID-19 positive) from 134 countries who provided 178,820 perceptual ratings of 60 different household odorants. Results: We observe that olfactory ratings are indicative of COVID-19 status in a country, significantly correlating with national infection rates over time. More importantly, we observe indicative power at the individual level (79% sensitivity and 87% specificity). Critically, this olfactory screen remains effective in participants with COVID-19 but without symptoms, and in participants with symptoms but without COVID-19. Conclusions: The current odorant-based olfactory screen adds a component to online symptom-checkers, to potentially provide an added first line of defense that can help fight disease progression at the population level. The data derived from this tool may allow better understanding of the link between COVID-19 and olfaction.

And I'm feeling good: effect of emotional sweat and perfume on others' physiology, verbal responses, and creativity.

Emotions can be communicated in social contexts through chemosignals contained in human body odors. The transmission of positive emotions via these signals has received little interest in past research focused mainly on negative emotional transmission. Furthermore, how the use of perfumed products might modulate this transmission remains poorly understood. To investigate human positive chemical communication, we explored the autonomic, verbal, and behavioral responses of receivers exposed to body odors of donors having undergone a within-subject positive or neutral mood induction procedure. These responses were compared with those obtained after exposure to the same body odors with added fragrance. Our findings suggest that positive emotions can be transmitted through body odor. They not only induced modifications at the physiological (heart rate) and verbal levels (perceived intensity and familiarity) but also at the behavioral level, with an improved performance on creativity tasks. Perfume did not modulate the physiological effects and had a synergistic effect on the positive body odor ratings (increased perceived differences between the neutral and positive body odor).

Blindness, But Not HMHA Anosmia, Predicts Loneliness: A Psychophysical Study.

Olfactory deficits can play a detrimental role in everyday social functioning. Perception of 3-hydroxy-3-methylhexanoic acid (HMHA)-a body odor component-could also be linked to this research area. However, no study so far has addressed the problem of HMHA perception in the context of the previously reported relationship between olfactory abilities and social difficulties. Here, we tested whether HMHA-specific anosmia predicted loneliness understood both as a cognitive evaluation of social participation and as one's social isolation, and we additionally analyzed the effects and correlates of HMHA perception in relation to sightedness. The study comprised 196 people, of whom 99 were blind. We found that subjects with blindness declared particularly high loneliness, but HMHA anosmia and the interaction of sightedness and HMHA anosmia predicted neither loneliness nor social withdrawal. In addition, HMHA pleasantness was positively associated with social withdrawal of the subjects with blindness and emotional loneliness correlated with HMHA familiarity regardless of sightedness.

The smell of cooperativeness: Do human body odours advertise cooperative behaviours?

Several physical features influence the perception of how cooperative a potential partner is. While previous work focused on face and voice, it remains unknown whether body odours influence judgements of cooperativeness and if odour-based judgements are accurate. Here, we first collected axillary odours of cooperative and uncooperative male donors through a public good game and used them as olfactory stimuli in a series of tasks examining whether and how they influence cooperative decision-making in an incentivized economic game and ratings of cooperativeness. Our results show that having access to the donor's body odours provided a strategic advantage to women during economic decisions (but not to men): with age, women were more likely to cooperate with cooperative men and to avoid interacting with uncooperative men. Ratings of cooperativeness were nonetheless unrelated to the donors' actual cooperativeness. Finally, while men with masculine and intense body odours were judged less cooperative, we found no evidence that donors' actual cooperativeness was associated with less masculine or less intense body odour. Overall, our findings suggest that, as faces and voices, body odours influence perceived cooperativeness and might be used accurately and in a non-aware manner as olfactory cues of cooperativeness, at least by women.

African Gene Flow Reduces Beta-Ionone Anosmia/Hyposmia Prevalence in Admixed Malagasy Populations.

While recent advances in genetics make it possible to follow the genetic exchanges between populations and their phenotypic consequences, the impact of the genetic exchanges on the sensory perception of populations has yet to be explored. From this perspective, the present study investigated the consequences of African gene flow on odor perception in a Malagasy population with a predominantly East Asian genetic background. To this end, we combined psychophysical tests with genotype data of 235 individuals who were asked to smell the odorant molecule beta-ionone (ßI). Results showed that in this population the ancestry of the OR5A1 gene significantly influences the ability to detect ßI. At the individual level, African ancestry significantly protects against specific anosmia/hyposmia due to the higher frequency of the functional gene (OR ratios = 14, CI: 1.8-110, p-value = 0.012). At the population level, African introgression decreased the prevalence of specific anosmia/hyposmia to this odorous compound. Taken together, these findings validate the conjecture that in addition to cultural exchanges, genetic transfer may also influence the sensory perception of the population in contact.

Recovery From COVID-19-Related Olfactory Disorders and Quality of Life: Insights From an Observational Online Study.

Although olfactory disorders (OD) are among the most significant symptoms of COVID-19, recovery time from COVID-19-related OD and their consequences on the quality of life remain poorly documented. We investigated the characteristics and behavioral consequences of COVID-19-related OD using a large-scale study involving 3111 French respondents (78% women) to an online questionnaire over a period of 9 months covering different epidemic waves (from 8 April 2020 to 13 January 2021). In the patients who subjectively recovered from COVID-19-related OD (N = 609), recovery occurred on average after 16 days and most of the time within 1 month ("normal" recovery range); 49 subjectively recovered in 1-2.5 months, and several cases took up to 6.5 months. Among the patients with ongoing OD (N = 2502), 974 were outside the "normal" recovery range (persistent OD) and reported OD for 1-10 months. Developing a persistent OD was more likely with increasing age and in women and was more often associated with parosmia and phantosmia. The deleterious impact of COVID-19-related OD on the quality of life was significantly aggravated by OD duration and was more pronounced in women. Because persistent OD is not infrequent after COVID-19, has deleterious consequences on the quality of life, and receives few solutions from the health practitioners, it would be beneficial to implement screening and treatment programs to minimize the long-term behavioral consequences of COVID-19-related OD.

Neural processing of the reward value of pleasant odorants.

Pleasant odorants are represented in the posterior olfactory bulb (pOB) in mice. How does this hedonic information generate odor-motivated behaviors? Using optogenetics, we report here that stimulating the representation of pleasant odorants in a sensory structure, the pOB, can be rewarding, self-motivating, and is accompanied by ventral tegmental area activation. To explore the underlying neural circuitry downstream of the olfactory bulb (OB), we use 3D high-resolution imaging and optogenetics and determine that the pOB preferentially projects to the olfactory tubercle, whose increased activity is related to odorant attraction. We further show that attractive odorants act as reinforcers in dopamine-dependent place preference learning. Finally, we extend those findings to humans, who exhibit place preference learning and an increase BOLD signal in the olfactory tubercle in response to attractive odorants. Thus, strong and persistent attraction induced by some odorants is due to a direct gateway from the pOB to the reward system.

The autumnal lockdown was not the main initiator of the decrease in SARS-CoV-2 circulation in France.

Background: In response to the SARS-CoV-2 pandemic, governments have taken drastically restrictive public health measures with significant collateral effects. It is important to understand the impact of these measures on SARS-CoV-2 circulation. However, pandemic indicators lag behind the actual level of viral circulation and these delays are an obstacle to assessing the effectiveness of policy decisions. Here, we propose one way to solve this problem by synchronizing the indicators with viral circulation in a country (France) based on a landmark event. Methods: Based on a first lockdown, we measured the time lag between the peak of governmental and non-governmental surveillance indicators and the highest level of virus circulation. This allowed alignment of all surveillance indicators with viral circulation during the second period of the epidemic, overlaid with the type of public health measures implemented. Results: We show that the second peak in viral circulation in France happened ~21 October 2020, during the public health state of emergency but before the lockdown (31 October). Indicators also suggest that viral circulation decreased earlier in locations where curfews were implemented. Indicators did, however, begin to rise once the autumnal lockdown was lifted and the state of emergency resumed. Conclusions: Overall, these results suggest that in France, the 2020 autumnal lockdown was not the main initiator of the decrease in SARS-CoV-2 circulation and curfews were important in achieving control of the transmission. Less-restrictive measures may need to be balanced with more-stringent measures to achieve desirable public health outcomes over time.

Smell and taste changes are early indicators of the COVID-19 pandemic and political decision effectiveness.

In response to the COVID-19 pandemic, many governments have taken drastic measures to avoid an overflow of intensive care units. Accurate metrics of disease spread are critical for the reopening strategies. Here, we show that self-reports of smell/taste changes are more closely associated with hospital overload and are earlier markers of the spread of infection of SARS-CoV-2 than current governmental indicators. We also report a decrease in self-reports of new onset smell/taste changes as early as 5 days after lockdown enforcement. Cross-country comparisons demonstrate that countries that adopted the most stringent lockdown measures had faster declines in new reports of smell/taste changes following lockdown than a country that adopted less stringent lockdown measures. We propose that an increase in the incidence of sudden smell and taste change in the general population may be used as an indicator of COVID-19 spread in the population.

Relationship between odor intensity estimates and COVID-19 prevalence prediction in a Swedish population.

In response to the COVID-19 pandemic, countries have implemented various strategies to reduce and slow the spread of the disease in the general population. For countries that have implemented restrictions on its population in a step-wise manner, monitoring of COVID-19 prevalence is of importance to guide decision on when to impose new, or when to abolish old, restrictions. We are here determining whether measures of odor intensity in a large sample can serve as one such measure. Online measures of how intense common household odors are perceived and symptoms of COVID-19 were collected from 2440 Swedes. Average odor intensity ratings were then compared to predicted COVID-19 population prevalence over time in the Swedish population and were found to closely track each other (r=-0.83). Moreover, we found that there was a large difference in rated intensity between individuals with and without COVID-19 symptoms and number of symptoms was related to odor intensity ratings. Finally, we found that individuals progressing from reporting no symptoms to subsequently reporting COVID-19 symptoms demonstrated a large drop in olfactory performance. These data suggest that measures of odor intensity, if obtained in a large and representative sample, can be used as an indicator of COVID-19 disease in the general population. Importantly, this simple measure could easily be implemented in countries without widespread access to COVID-19 testing or implemented as a fast early response before wide-spread testing can be facilitated.

Interdisciplinary challenges for elucidating human olfactory attractiveness.

Many species use chemicals to communicate. In humans, there is increasing evidence that chemicals conveyed by the body are extremely important in interpersonal relationships. However, many aspects of chemical communication remain to be explored to fully understand this function in humans. The aim of this article is to identify relevant challenges in this field, with a focus on human attractiveness in the context of reproduction, and to put forward roadmaps for future studies that will hopefully extend to a wider range of social interactions. The first challenge consists in not being limited to body (mal)odours from the axilla. Preliminary data on how the odour of the face and head is perceived are presented. Second, there is a crucial need to increase our knowledge of the chemical bases of human chemical communication. Third, cross-cultural approaches must not be overlooked, because they have a major input in understanding the universal and culture-specific aspects of chemical communication. Fourth, the influence of specific cultural practices such as contraceptive and fragrance use is likely to be prominent and, therefore, needs to be well described. The fifth and last challenge for research projects in this field is the integration of different disciplines such as behavioural sciences, social sciences, neurosciences and microbiology. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.

Visual Priming Influences Olfactomotor Response and Perceptual Experience of Smells.

Whereas contextual influences in the visual and auditory domains have been largely documented, little is known about how chemical senses might be affected by our multisensory environment. In the present study, we aimed to better understand how a visual context can affect the perception of a rather pleasant (floral) and a rather unpleasant (damp) odor. To this end, 19 healthy participants performed a series of tasks including odor detection followed by perceptual evaluations of odor intensity, pleasantness, flowery, and damp characters of both odors presented at 2 different concentrations. A visual context (either congruent or incongruent with the odor; or a neutral control context) preceded odor stimulations. Olfactomotor responses as well as response times were recorded during the detection task. Results showed an influence of the visual context on semantic and motor responses to the target odors. First, congruency between context and odor increased the saliency of the olfactory feature of the memory trace, for the pleasant floral odor only (higher perceived flowery note). Clinical applications of this finding for olfactory remediation in dysosmic patients are proposed. Second, the unpleasant odor remained unaffected by visual primes, whatever the condition. In addition, incongruency between context and odor (regardless of odor type) had a disruptive effect on odor sampling behavior, which was interpreted as a protective behavior in response to expectancy violation. Altogether, this second series of effects may serve an adaptive function, especially the avoidance of, or simply vigilance toward, aversive and unpredictable stimuli.

Individual Differences as a Key Factor to Uncover the Neural Underpinnings of Hedonic and Social Functions of Human Olfaction: Current Findings from PET and fMRI Studies and Future Considerations.

The hedonic and social dimensions of olfactory perception are characterized by a great diversity across people. Whereas the cerebral processing underlying these aspects of odor perception have been widely explored in the last decades, very few brain imaging studies considered individual differences. This lack of consideration weakens the current models in the field, where the paradigm of universality is the norm. The present review is aimed at examining this issue. Through a synthetic summary, we will first present past studies suggesting that (1) hedonics are represented consistently throughout the olfactory system from primary to secondary areas, with a progressive cognitive modulation and integration with other senses, (2) social dimension of odors may be represented in a distinct pathway involving social and attentional networks. In a second, and more critical part, we will highlight the importance of individual differences for the cerebral study of human olfaction.

Influence of gender and culture on the perception of acidic compounds of human body odor.

There is increasing evidence that human body odor is involved in interpersonal communication. However, among the wide variety of substances excreted by the human body that might act as chemosignals, much attention has been granted to androstenes to the detriment of other categories. Here, we focused on the acidic fraction of human body odor. We investigated men and women's perceptual descriptions and detection thresholds of the sexually dimorphic (male) compound 3-hydroxy-3-methylhexanoic acid (HMHA) in two contrasted cultures, France and Madagascar. Perceptual responses to HMHA in both countries were very similar. HMHA proved to be more typical of body odor than another chemically-related major compound of human body odor 3MHA (3-methylhex-2-enoic acid also known as 3M2H). A significant portion of the samples studied (between 8 and 19%) was likely to be anosmic to HMHA (and to 3MHA: 25%). Although differences would be expected between men and women's perceptual responses to HMHA, based on the assumption that this compound would have a function in human partner choice, no sex differences were found for any of the perceptual variables. However, in Malagasy women, perceived intensity of HMHA was higher in participants who were in the fertile phase of the menstrual cycle. Whether HMHA is relevant in the perception of a potential partner thus requires further explorations, with more implicit approaches for example and/or by investigating the repercussions of HMHA specific anosmia on interpersonal relationships.