Chronic inflammatory process in the nasal mucosa is correlated with poor smell perception. Over-activation of immune cells in the olfactory epithelium (OE) is generally associated with loss of olfactory function, and topical steroidal anti-inflammatory drugs have been largely used for treating such condition. Whether this therapeutic strategy could directly affect the regenerative process in the OE remains unclear. In this study, we show that nasal topical application of dexamethasone (DEX; 200 or 800 ng/nostril), a potent synthetic anti-inflammatory steroid, attenuates OE lesion caused by Gram-negative bacteria lipopolysaccharide (LPS) intranasal infusion. In contrast, repeated DEX (400 ng/nostril) local application after lesion establishment limited the regeneration of olfactory sensory neurons after injury promoted by LPS or methimazole. Remarkably, DEX effects were observed when the drug was infused as 3 consecutive days regimen. The anti-inflammatory drug does not induce OE progenitor cell death, however, disturbance in mammalian target of rapamycin downstream signaling pathway and impairment of protein synthesis were observed during the course of DEX treatment. In addition, in vitro studies conducted with OE neurospheres in the absence of an inflammatory environment showed that glucocorticoid receptor engagement directly reduces OE progenitor cells proliferation. Our results suggest that DEX can interfere with the intrinsic regenerative cellular mechanisms of the OE, raising concerns on the use of topical anti-inflammatory steroids as a risk factor for progressive olfactory function impairment.

The sensory neurons in the olfactory epithelium (OSNs) are equipped with a large repertoire of olfactory receptors and the associated signal transduction machinery. In addition to the canonical OSNs, which express odorant receptors (ORs), the epithelium contains specialized subpopulations of sensory neurons that can detect specific information from environmental cues and relay it to relevant neuronal circuitries. Here we describe a subpopulation of mature OSNs in the main olfactory epithelium (MOE) which expresses CD36, a multifunctional receptor involved in a series of biological processes, including sensory perception of lipid ligands. The Cd36 expressing neurons coexpress markers of mature OSNs and are dispersed throughout the MOE. Unlike several ORs analyzed in our study, we found frequent coexpression of the OR Olfr287 in these neurons, suggesting that only a specific set of ORs may be coexpressed with CD36 in OSNs. We also show that CD36 is expressed in the cilia of OSNs, indicating a possible role in odorant detection. CD36-deficient mice display no signs of gross changes in the organization of the olfactory epithelium, but show impaired preference for a lipid mixture odor. Our results show that CD36-expressing neurons represent a distinct population of OSNs, which may have specific functions in olfaction.

Upper respiratory viral infections can decrease the sense of smell either by inflammatory restriction of nasal airflow that carries the odorant molecules or through interference in olfactory sensory neuron function. During the coronavirus disease 2019 (COVID-19) pandemic, triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), worldwide reports of severe smell loss (anosmia/hyposmia) revealed a different type of olfactory dysfunction associated with respiratory virus infection. Since self-reported perception of smell is subjective and SARS-CoV-2 exposure is variable in the general population, we aimed to study a population that would be more homogeneously exposed to the virus. Here, we investigated the prevalence of olfactory loss in frontline health professionals diagnosed with COVID-19 in Brazil, one of the major epicenters of the disease. We also analyzed the rate of olfactory function recovery and the particular characteristics of olfactory deficit in this population. A widely disclosed cross-sectional online survey directed to health care workers was developed by a group of researchers to collect data concerning demographic information, general symptoms, otolaryngological symptoms, comorbidities, and COVID-19 test results. Of the 1,376 health professionals who completed the questionnaire, 795 (57.8%) were working directly with COVID-19 patients, either in intensive care units, emergency rooms, wards, outpatient clinics, or other areas. Five-hundred forty-one (39.3%) participants tested positive for SARS-CoV-2, and 509 (37%) were not tested. Prevalence of olfactory dysfunction in COVID-19-positive subjects was 83.9% (454 of 541) compared to 12.9% (42 of 326) of those who tested negative and to 14.9% (76 of 509) of those not tested. Olfactory dysfunction incidence was higher in those working in wards, emergency rooms, and intensive care units compared to professionals in outpatient clinics. In general, remission from olfactory symptoms was frequent by the time of responses. Taste disturbances were present in 74.1% of infected participants and were significantly associated with hyposmia. In conclusion, olfactory dysfunction is highly correlated with exposure to SARS-CoV-2 in health care professionals, and remission rates up to 2 weeks are high.

Olfaction plays a critical role in several aspects of the human life. Odorants are detected by hundreds of odorant receptors (ORs) which belong to the superfamily of G protein-coupled receptors. These receptors are expressed in the olfactory sensory neurons of the nose. The information provided by the activation of different combinations of ORs in the nose is transmitted to the brain, leading to odorant perception and emotional and behavioral responses. There are ~400 intact human ORs, and to date only a small percentage of these receptors (~10%) have known agonists. The determination of the specificity of the human ORs will contribute to a better understanding of how odorants are discriminated by the olfactory system. In this work, we aimed to identify human specific ORs, that is, ORs that are present in humans but absent from other species, and their corresponding agonists. To do this, we first selected 22 OR gene sequences from the human genome with no counterparts in the mouse, rat or dog genomes. Then we used a heterologous expression system to screen a subset of these human ORs against a panel of odorants of biological relevance, including foodborne aroma volatiles. We found that different types of odorants are able to activate some of these previously uncharacterized human ORs.