High prevalence of long-term olfactory dysfunction confirmed by olfactory testing after a community COVID-19 outbreak

Purpose The prevalence of long-term olfactory and gustatory dysfunction in participants suffering from sudden chemosensory loss due to coronavirus disease 2019 (COVID-19) is unknown. Furthermore, evaluations of the reliability of participants’ self-reporting of olfactory function (SOF) and gustatory function (SGF) using extended objective psychophysical testing are missing. Methods In this population-based cohort study in a PCR-tested community in Thuringia, Germany, olfactory function was extensively examined 4 months after a COVID-19 outbreak using the “Sniffin Sticks” test battery to determine the TDIa score, i.e., the sum of results obtained for threshold, discrimination, and identification scores averaged for both nasal sides. Gustatory function was assessed using the three-drop test resulting in the gustatory composite score (CSg). The data were compared with SOF and SGF. Results Of 43 adult convalescents (median age: 68 years; 58% female) after SARS-CoV‑2 infection, 18 participants (42%) had olfactory complaints due to SOF, one participant (2%) complained of taste disturbance due to SGF. The TDIa was 22.0 ± 5.9. Normosmia, hyposmia, and anosmia were seen in 17, 18, and eight participants, respectively. TDIa correlated with SOF (rs = −0.434, p = 0.004); CSg was 23.5 ± 2.7. Normogeusia and hypogeusia were objectified in 39 and four participants, respectively. The prevalence of long-term olfactory dysfunction and gustatory dysfunction in the study group was 60.5 and 9.3%, respectively. Conclusion The SOF was reliable, especially for participants who felt a sudden chemosensory dysfunction during the outbreak. At 4 months after SARS-CoV‑2 infection, a high proportion of participants were dysosmic, whereas nearly all of them had normal taste function.

Randomised trial of the P2X3 receptor antagonist sivopixant for refractory chronic cough

BackgroundThe purinoceptor subtype P2X3 has been shown to have significant involvement in the cough reflex; the heterotrimer version of the purinoceptor (P2X2/3) has been implicated in taste disturbance. The most advanced clinical candidate antagonist gefapixant has low selectivity among P2X3 receptors and induced taste disturbance, whereas newly developed sivopixant has high selectivity towards P2X3versus P2X2/3.MethodsIn a phase 2a, randomised, double-blind, placebo-controlled, crossover, multicentre study, adult patients with refractory or unexplained chronic cough received oral sivopixant 150 mg or placebo once daily for 2 weeks, followed by a 2–3-week washout period, and then crossed over to placebo or sivopixant for 2 weeks. Efficacy and safety of sivopixant were evaluated.ResultsOf 31 randomised patients, 15 in the sivopixant-first group and 15 in the placebo-first group completed the study. After 2 weeks’ treatment, the placebo-adjusted ratios of the average hourly number of coughs to baseline during daytime (primary endpoint) and over 24 h (secondary endpoint) were −31.6% (p=0.0546) and −30.9% (p=0.0386), respectively. Sivopixant also improved health-related quality of life. Treatment-related adverse events occurred in 12.9% and 3.2% of patients during sivopixant and placebo administration, respectively. Mild taste disturbance occurred in two patients (6.5%) during sivopixant administration.ConclusionsSivopixant reduced objective cough frequency and improved health-related quality of life, with a low incidence of taste disturbance, among patients with refractory or unexplained chronic cough.

Neurological manifestations and complications of COVID-19. A literature review

Introduction. The first case of SARS-CoV-2 infection was identified in December 2019 in Wuhan, China. The disease spread rapidly worldwide and the WHO declared a pandemic on March 11, 2020. Although coronavirus disease 2019 (COVID-19) has been associated primarily with respiratory disorders, more and more research is focusing on neurological manifestations and complications.Objective. The aim of the review is to systematize and update the knowledge and available research on neurological complications among COVID-19 patients.Review methods. A systematic search of PubMed and Google Scholar databases was conducted for studies. The following keywords combinations were used: COVID-19, SARS-CoV-2 infection, neurological complications, neurological manifestations, neuroinvasion, neurovirulence.Results. The disease in most patients is characterized by mild to medium fever, fatigue, dry cough, dyspnea, muscle pain and headache. ACE2, which is the receptor for SARS-COV-2, is ubiquitously expressed in a variety of human organs, including the brain. Following previous reports, these receptors are expressed in both glial cells and neurons. Many studies have reported neurological symptoms and complications among COVID-19 patients. The reported manifestations include: smell and taste disturbance, non-specific symptoms such as myalgia, headache and dizziness, acute cerebrovascular complications, encephalopathy, meningoencephalitis/encephalitis, seizure and complications of the peripheral nervous system.Conclusion. Healthcare professionals dealing with COVID-19, neuroscientists, and the general public should be aware of the neurological complications of COVID-19. Further studies are needed to assess the incidence of COVID-19 neurological complications in different populations and more analyzes are also required to understand the detailed mechanism of how the virus affects the nervous system.

Disorders of Taste and Smell

Among sensory abilities, smell and taste are the mechanisms through which humans sample chemicals in the environment, also known as chemoreception. These chemosensory abilities allow us to appreciate pleasurable environmental stimuli and provide critical information for the avoidance of potentially toxic compounds or environmental dangers. Correspondingly, dysfunction of these sensory abilities has repercussions not only for quality of life, but also personal safety. In this module, we will undertake an in-depth discussion of chemosensory dysfunction beginning with definitions of olfactory dysfunction and taste disturbance and associated epidemiology. Normal physiology and pathophysiology of chemosensory disorders are reviewed, along with associations of chemosensory disorders to other diseases of the head and neck. An overview of appropriate components of patient history and physical examination follows, with a discussion of indications for further testing. Finally, treatment modalities and patient outcomes for olfactory dysfunction and taste disturbance are highlighted. This review contains 3 figures, 8 tables and 76 references. Key Words: Olfactory Dysfunction, Gustatory Dysfunction, Chemosensation, Evaluation of smell loss, Evaluation of taste loss, Olfactory Training

Menopausal symptoms are associated with oral sensory complaints in perimenopausal women: an observational study

Background Perimenopausal women experience a wide variety of systemic symptoms: hot flashes, sweating, mental health concerns and various oral sensory complaints (OSC). OSC in perimenopausal women include xerostomia, taste disturbance and burning mouth. However, the factors associated with these OSC have not been identified. The purpose of this investigation was to elucidate the factors associated with OSC in perimenopausal women. Methods The study cohort comprised 43 perimenopausal women aged 45–55 years. Data on medical history, medications, menstrual status, menopausal symptoms, quality of life, xerostomia, taste disturbance and burning mouth were collected. Volumes of unstimulated and stimulated saliva were measured. Tongue coating was evaluated according to a tongue coating index. Univariate analysis was performed to identify factors significantly associated with having xerostomia, taste disturbance, burning mouth and more than two OSC (2OSC). Next, the factors strongly associated with these symptoms were examined by logistic regression analysis. Results The number of menopausal symptoms was significantly higher, and volume of unstimulated saliva was significantly lower in participants with xerostomia, taste disturbance, burning mouth or 2OSC than in those without these characteristics. Agents targeting the central nervous system were more frequently taken by participants with burning mouth and 2OSC than by those without these characteristics. According to logistic regression analysis, the number of menopausal symptoms was an explanatory variable for xerostomia, taste disturbance, burning mouth and 2OSC. Conclusions Our findings suggested that OSC associated with the number of menopausal symptoms. Management of menopausal symptoms may decrease OSC, leading to improved quality of life of perimenopausal women.

Metallic foreign body adjacent to the round window: a rare cause for chronic tympanic membrane perforation with hearing loss

Welding injuries to the tympanic membrane (TM) or middle ear are rare but can cause significant damage. These injuries occur when a hot spark or molten slag drops directly into the external auditory canal and through the action of gravity (because the ear is upright during such an injury), then risks burning through the TM. This can lead to a multitude of adverse consequences including chronic TM perforation, secondary purulent otorrhoea, facial palsy, taste disturbance, vertigo and hearing loss. We present the case of a welding injury to the right TM, resulting in a chronic perforation and hearing loss. The patient required surgical intervention for removal of the metallic foreign body and repair of the TM. The patient obtained a good surgical result with no sensorineural hearing loss. This is a preventable occupational injury, which can be avoided by use of ear protection and increased awareness of this potential risk.

The Tryptophan/Kynurenine Pathway: A Novel Cross-Talk between Nutritional Obesity, Bariatric Surgery and Taste of Fat

Diet-induced obesity (DIO) reduces the orosensory perception of lipids in rodents and in some humans. Although bariatric surgery partially corrects this alteration, underlying mechanisms remain poorly understood. To explore whether metabolic changes might explain this fat taste disturbance, plasma metabolome analyses, two-bottle choice tests and fungiform papillae (Fun) counting were performed in vertical sleeve gastrectomized (VSG) mice and sham-operated controls. An exploratory clinic study was also carried out in adult patients undergone a VSG. In mice, we found that (i) the VSG reduces both the plasma neurotoxic signature due to the tryptophan/kynurenine (Trp/Kyn) pathway overactivation and the failure of fat preference found in sham-operated DIO mice, (ii) the activity of Trp/Kyn pathway is negatively correlated to the density of Fun, and (iii) the pharmacological inhibition of the Kyn synthesis mimics in non-operated DIO mice the positive effects of VSG (i.e., decrease of Kyn synthesis, increase of Fun number, improvement of the fat taste perception). In humans, a reduction of the plasma Kyn level is only found in patients displaying a post-surgery improvement of their fat taste sensitivity. Altogether these data provide a plausible metabolic explanation to the degradation of the orosensory lipid perception observed in obesity.