-
Frontiers in Human Neuroscience 2024COVID-19's effects on the human brain reveal a multifactorial impact on cognition and the potential to inflict lasting neuronal damage. Type I interferon signaling, a...
COVID-19's effects on the human brain reveal a multifactorial impact on cognition and the potential to inflict lasting neuronal damage. Type I interferon signaling, a pathway that represents our defense against pathogens, is primarily affected by COVID-19. Type I interferon signaling, however, is known to mediate cognitive dysfunction upon its dysregulation following synaptopathy, microgliosis and neuronal damage. In previous studies, we proposed a model of outside-in dysregulation of tonic IFN-I signaling in the brain following a COVID-19. This disruption would be mediated by the crosstalk between central and peripheral immunity, and could potentially establish feed-forward IFN-I dysregulation leading to neuroinflammation and potentially, neurodegeneration. We proposed that for the CNS, the second-order mediators would be intrinsic disease-associated molecular patterns (DAMPs) such as proteopathic seeds, without the requirement of neuroinvasion to sustain inflammation. Selective vulnerability of neurogenesis sites to IFN-I dysregulation would then lead to clinical manifestations such as anosmia and cognitive impairment. Since the inception of our model at the beginning of the pandemic, a growing body of studies has provided further evidence for the effects of SARS-CoV-2 infection on the human CNS and cognition. Several preclinical and clinical studies have displayed IFN-I dysregulation and tauopathy in gene expression and neuropathological data in new cases, correspondingly. Furthermore, neurodegeneration identified with a predilection for the extended olfactory network furthermore supports the neuroanatomical concept of our model, and its independence from fulminant neuroinvasion and encephalitis as a cause of CNS damage. In this perspective, we summarize the data on IFN-I as a plausible mechanism of cognitive impairment in this setting, and its potential contribution to Alzheimer's disease and its interplay with COVID-19.
PubMed: 38562226
DOI: 10.3389/fnhum.2024.1352118 -
Cureus Feb 2024Purpose New-onset loss of olfaction and/or taste is now recognized among the hallmark symptoms of COVID-19. In most patients, these symptoms resolve completely and...
Purpose New-onset loss of olfaction and/or taste is now recognized among the hallmark symptoms of COVID-19. In most patients, these symptoms resolve completely and spontaneously within days. However, some patients experience persistent olfactory and gustatory dysfunction after COVID-19 resolution. We evaluated the efficacy of a treatment combining several therapeutic agents to target inflammation and endothelial dysfunction in patients with persistent hyposmia and dysgeusia. Methods This 12-month observational pilot study involved patients presenting with symptoms of hyposmia and dysgeusia 30 days after COVID-19 had subsided. The main objective was to evaluate the efficacy of a combination of systemic corticosteroids, a glycosaminoglycan (GAG)-based antithrombotic (mesoglycan), a diuretic, and a vitamin complex. The perceived extent of olfaction and taste impairment was assessed using an 11-point visual analog scale (VAS), where 0 = complete loss of olfaction/taste and 10 = complete recovery of olfaction/taste. Results Eighty-seven patients with post-COVID-19 hyposmia and dysgeusia were enrolled. At treatment start (T0), the mean VAS scores were 2.0 and 3.2 for olfactory and gustatory functions, respectively. Both functions appeared to improve progressively and significantly from T0 to 12 months. A shorter time between viral infection and the start of treatment was associated with a more pronounced recovery of both senses. Conclusions Combined systemic corticosteroid, GAG-based antithrombotic agent (mesoglycan), and diuretic may constitute an option for treating persistent hyposmia and dysgeusia associated with COVID-19. To ensure optimal recovery, early treatment start is recommended. The described treatment protocol deserves to be further evaluated.
PubMed: 38544584
DOI: 10.7759/cureus.54925 -
Microorganisms Mar 2024Acute respiratory viruses (ARVs) are the leading cause of diseases in humans worldwide. High-risk individuals, including children and the elderly, could potentially... (Review)
Review
Acute respiratory viruses (ARVs) are the leading cause of diseases in humans worldwide. High-risk individuals, including children and the elderly, could potentially develop severe illnesses that could result in hospitalization or death in the worst case. The most common ARVs are the Human respiratory syncytial virus, Human Metapneumovirus, Human Parainfluenza Virus, rhinovirus, coronaviruses (including SARS and MERS CoV), adenoviruses, Human Bocavirus, enterovirus (-D68 and 71), and influenza viruses. The olfactory deficits due to ARV infection are a common symptom among patients. This review provides an overview of the role of SARS-CoV-2 and other common ARVs in the development of human olfactory pathophysiology. We highlight the critical need to understand the signaling underlying the olfactory dysfunction and the development of therapeutics for this wide-ranging category of AVRs to restore the altered or loss of smell in affected patients.
PubMed: 38543591
DOI: 10.3390/microorganisms12030540 -
Life (Basel, Switzerland) Feb 2024(1) Background: One of the possible symptoms of COVID-19 is a sudden loss of smell and taste. The main aim of the study was to evaluate the severity of post-COVID-19...
(1) Background: One of the possible symptoms of COVID-19 is a sudden loss of smell and taste. The main aim of the study was to evaluate the severity of post-COVID-19 olfactory dysfunction (OD). A secondary aim was to assess the relationship between OD and gustatory (taste) dysfunction (GD). Margins: 2.5 cm (1 inch) at top, bottom, right, and left. (2) Methods: The study group consisted of 81 subjects (16 men and 65 women) aged between 12 and 73 years. All of the patients presented to a center for subjective OD associated with COVID-19. They were tested with a Sniffin' Sticks test (SST) for OD and a Taste Strip test (TS) for GD. (3) Anosmia was present in 18 participants (22%), hyposmia in 52 (64%), and normosmia in 11 (14%). Some 36% of the patients reported imaginary smells (phantosmia), but it did not correlate with olfactory sensitivity. Comparing the different parts of the SST showed that subjects scored lowest on the threshold part of the test. The results of the discrimination and identification parts of the test were better, implying that if the stimulus is intense enough, incorrect discrimination and identification of odors is less frequent. A sweet taste was the easiest to recognize (78% could do so), while the most difficult to recognize was salty (68%). There were weak and statistically non-significant correlations between olfactory and taste dysfunction. (4) Conclusions: The results suggest that post-COVID-19 olfactory dysfunction was more peripheral than central. Testing patients for the severity of post-COVID-19 OD may help clinicians treat the condition. Because there is no fully effective treatment, research on post-COVID-19 OD is needed.
PubMed: 38541643
DOI: 10.3390/life14030317 -
Life (Basel, Switzerland) Feb 2024Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between...
BACKGROUND
Among all studies describing COVID-19 clinical features during the first wave of the pandemic, only a few retrospective studies have assessed the correlation between olfac-tory dysfunction (OD) and the evolution of disease severity. The main aim was to assess whether OD is a predictive factor of COVID-19 severity based on the patient's medical management (outpa-tient care, standard hospital admission, and ICU admission).
METHODS
A national, prospective, mul-ticenter cohort study was conducted in 20 public hospitals and a public center for COVID-19 screen-ing. During the first wave of the pandemic, from 6 April to 11 May 2020, all patients tested positive for COVID-19 confirmed by RT-PCR underwent two follow-up ENT consultations within 10 days of symptom onset. The main outcome measures were the evolution of medical management (out-patient care, standard hospital admission, and ICU admission) at diagnosis and along the clinical course of COVID-19 disease.
RESULTS
Among 481 patients included, the prevalence of OD was 60.7%, and it affected mostly female patients (74.3%) under 65 years old (92.5%), with fewer comor-bidities than patients with normal olfactory function. Here, 99.3% (290/292) of patients with OD presented with non-severe COVID-19 disease. Patients reporting OD were significantly less hospi-talized than the ones managed as outpatients, in either a standard medical unit or an ICU. Conclu-sions: As regards the clinical course of COVID-19 disease, OD could predict a decreased risk of hospitalization during the first wave of the pandemic.
PubMed: 38541618
DOI: 10.3390/life14030293 -
Frontiers in Genetics 2024Pubertal delay can be due to hypogonadotropic hypogonadism (HH), which may occur in association with anosmia or hyposmia and is known as Kallmann syndrome (OMIM...
Pubertal delay can be due to hypogonadotropic hypogonadism (HH), which may occur in association with anosmia or hyposmia and is known as Kallmann syndrome (OMIM #308700). Recently, hypogonadotropic hypogonadism has been suggested to overlap with Witteveen-Kolk syndrome (WITKOS, OMIM #613406) associated with 15q24 microdeletions encompassing . Whether hypogonadotropic hypogonadism is due to haploinsufficiency of or any of the other eight genes present in 15q24 is not known. We report the case of a female patient with delayed puberty associated with intellectual disability, behavior problems, dysmorphic facial features, and short stature, at the age of 14 years. Clinical, laboratory, and imaging assessments confirmed the diagnosis of Kallmann syndrome. Whole-exome sequencing identified a novel heterozygous frameshift variant, NM_001145358.2:c.3045_3046dup, NP_001138830.1:p.(Ile1016Argfs*6) in , classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG/AMP) criteria. Reverse phenotyping led to the clinical diagnosis of WITKOS. No other variant was found in the 96 genes potentially related to hypogonadotropic hypogonadism. The analysis of the other contiguous seven genes to in 15q24 did not reveal any clinically relevant variant. In conclusion, these findings point to as the gene in 15q24 related to the reproductive phenotype in patients with overlapping WITKOS and Kallmann syndrome.
PubMed: 38528912
DOI: 10.3389/fgene.2024.1354715 -
International Forum of Allergy &... May 2024Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory... (Review)
Review
Historically, comprehensive surgical resection for olfactory neuroblastoma has included the bilateral olfactory epithelium, cribriform plate, overlying dura, olfactory bulbs and tracts. This results in postoperative anosmia that may significantly impact a patient's quality of life without definitive added benefit in survival. The prevalence of occult intracranial disease is low, especially for Hyams grade I and II tumors. A unilateral approach sparing the contralateral cribriform plate and olfactory system can be considered for select cases of early stage, low-grade tumors when the disease does not cross midline to involve the contralateral olfactory cleft or septal mucosa and when midline dural margins can be cleared with frozen pathology. Approximately half of patients who undergo unilateral resection may have residual olfaction even with adjuvant unilateral radiation. Early data suggest favorable disease-free survival and overall survival for patients who underwent the unilateral approach; however, larger sample studies are needed to confirm comparability to bilateral resections regarding oncologic outcomes.
Topics: Humans; Esthesioneuroblastoma, Olfactory; Nose Neoplasms; Nasal Cavity; Smell; Treatment Outcome
PubMed: 38526915
DOI: 10.1002/alr.23345 -
Auris, Nasus, Larynx Jun 2024Different olfactory tests have been performed by otorhinolaryngologists in different parts of the world. For example, the University of Pennsylvania Smell Identification...
OBJECTIVE
Different olfactory tests have been performed by otorhinolaryngologists in different parts of the world. For example, the University of Pennsylvania Smell Identification Test (UPSIT) has been used in the U.S., whereas the Sniffin' Sticks Test has been used in Europe, and similarly, T&T olfactometry is used in Japan. Although audiometers with electronic oscillators have long been used in hearing tests, electronic odor generators are not typically used in olfaction tests. We attempted an olfactory test using the AROMASTIC® (SONY, Tokyo, Japan), an electronically controlled device that can diffuse five different odors.
METHODS
Forty participants who had visited an outpatient olfactory clinic were included in this study. The participants were instructed to answer whether they could smell the five different odors during the AROMASTIC® screening test (AS-test), and the number of odors smelled was summed and scored (AS-score). The patients also underwent T&T olfactometry concurrently.
RESULTS
The AS-scores and T&T olfactometry detection and recognition thresholds showed significant correlations, confirming that the AS-test is a valid olfactory test.
CONCLUSION
Electronic odor diffusers may be useful for olfaction tests.
Topics: Humans; Female; Male; Adult; Middle Aged; Odorants; Olfaction Disorders; Aged; Smell; Olfactometry; Sensory Thresholds; Young Adult
PubMed: 38522354
DOI: 10.1016/j.anl.2023.12.004 -
Auris, Nasus, Larynx Jun 2024Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well...
OBJECTIVE
Olfactory and gustatory functions are important sensory aspects in humans. Although they are believed to influence each other, their interrelationship is not well understood. In this study, we aimed to investigate the relationship between the olfactory and gustatory functions based on the results of a large-scale epidemiological study (Iwaki Health Promotion Project) of the general local population.
METHODS
We analyzed 565 participants who underwent taste and olfactory tests in the 2019 Iwaki Project. Gustatory function was tested for four taste qualities (sweet, sour, salty, and bitter) using whole-mouth taste tests. Olfactory function was tested using the University of Pennsylvania Smell Identification Test modified for Japanese (UPSIT-J). We evaluated sex-related differences between olfactory and gustatory functions and the effects of various factors on olfactory identification using multivariate analysis. Furthermore, we compared the percentage of accurate UPSIT-J responses between the normal and hypogeusia groups. We also analyzed the effects of taste and olfactory functions on eating.
RESULTS
Olfactory and gustatory functions were lower in men than in women. Among the four taste qualities, salty taste was the most closely associated with olfactory identification ability, with lower olfactory scores of salty taste in the hypogeusia group than in the normal group. Moreover, the hyposmia group had higher daily salt intake than the normal olfaction group in women.
CONCLUSION
These results suggest that olfactory identification tests may be useful in predicting elevated salt cognitive thresholds, leading to a reduction in salt intake, which may contribute to hypertension prevention.
Topics: Humans; Male; Female; Middle Aged; Adult; Japan; Aged; Health Promotion; Sex Factors; Smell; Taste; Ageusia; Olfaction Disorders; Anosmia; Taste Perception
PubMed: 38520975
DOI: 10.1016/j.anl.2023.12.009 -
Journal of Parkinson's Disease Mar 2024During its pre-motor stage, Parkinson's disease (PD) presents itself with a multitude of non-motor symptoms with different degrees of specificity and sensitivity. The... (Review)
Review
During its pre-motor stage, Parkinson's disease (PD) presents itself with a multitude of non-motor symptoms with different degrees of specificity and sensitivity. The most important among them are REM sleep behavior disorder (RBD) and olfactory dysfunction. RBD is a parasomnia characterized by the loss of REM sleep muscle atonia and dream-enacting behaviors. Olfactory dysfunction in individuals with prodromal PD is usually described as hyposmia (reduced sense of smell) or anosmia (complete loss of olfactory function). These symptoms can precede the full expression of motor symptoms by decades. A close comprehension of these symptoms and the underlying mechanisms may enable early screening as well as interventions to improve patients' quality of life. Therefore, these symptoms have unmatched potential for identifying PD patients in prodromal stages, not only allowing early diagnosis but potentially opening a window for early, possibly disease-modifying intervention. However, they come with certain challenges. This review addresses some of the key opportunities and pitfalls of both RBD and olfactory dysfunction as early markers of PD.
PubMed: 38517805
DOI: 10.3233/JPD-230348