Mechanisms of olfactory impairment in COVID-19: a systematic review

One of the symptoms of a new coronavirus infection (COVID-19) is a complete or partial violation of the sense of smell. The aim of the work is to analyze the published results of scientific research on the mechanisms of olfactory impairment in COVID-19. Material and methods. Research was conducted for publications in Pubmed on the problem of olfactory impairment in COVID-19 using terms indexed by MeSH. The systematic review was compiled in accordance with the checklist Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA). Results. Publication's analysis has shown that the existing ideas about conductive anosmia are insufficient to explain the causes of olfactory impairment caused by SARS-CoV-2. It has been established that ACE2 and TMPRSS2 receptors located on the surface of target cells are necessary for the penetration of a new coronavirus. It is known that these receptors are mainly located on the cells of the olfactory epithelium. The main hypothesis of olfactory impairment in COVID-19 is that anosmia/hyposmia is caused by damage not to neuronal cells (as previously assumed), but to the olfactory epithelium. There is no confirmation of the point of view about the damage of SARS-CoV-2 olfactory bulbs and olfactory neurons, since they do not express receptor proteins for the virus on their surface.Copyright © 2022 by the authors.

The olfactory bulb - gateway for SARS-Cov-2?

Introduction. Anosmia and ageusia are one of the most common and characteristic symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) infection, with a frequency of almost 50% in patients in Western countries. Hypotheses proposing that the virus potentially affects the central nervous system (CNS) are on the rise. One hypothesis suggests that the virus enters via nasal mucosa and then enters the olfactory bulb via cribriform plate, with further dissemination to the CNS. Case report. A 34-year-old female patient experienced the loss of the sense of smell and taste about two months before testing positive for SARS-Cov-2. Coronavirus disease 2019 (COVID- 19) presented with minor pneumonia and worsening anosmia and ageusia. After treatment, the patient recovered well, but anosmia and ageusia appeared again, varying in intensity, and since February 2021, they have become persistent. The case was evaluated by an otorhinolaryngologist, pulmonologist, and finally, a neurologist. In the meantime, the patient tested negative for SARS-Cov-2 and received two doses of the Sputnik V vaccine. Brain magnetic resonance imaging (MRI) was performed, and it clearly showed severe bilateral olfactory bulb atrophy. The patient has had anosmia and ageusia up to this day, and future MRI follow- up is planned. Conclusion. Loss of sense of smell and taste may be a predictor of further CNS dissemination of the virus and possible neurological complications (which is still a subject of consideration). The olfactory bulb could be a gateway to COVID-19 intrusion into the CNS, and its atrophy could be an indicator of the process. Further investigation on this topic is required, including a wide application of MRI, in order to come to definite conclusions.

OLFACTORY FUNCTION AND BRAIN STRUCTURAL EFFECTS FOLLOWING SARS-CoV-2 INFECTION

Background: SARS-CoV-2 infection is accompanied by acute olfactory disturbance in as high as 70% of cases. This loss is associated with decreased olfactory bulb volume. As time passes, the anosmia tends to subside, but the OB volume decrease does not. Volume reductions in primary and secondary olfactory cortex are also seen following SARS-CoV-2 infection. Nevertheless, concurrent SARS-CoV-2 infection effects on olfactory discrimination, olfactory bulb volume, primary olfactory cortex and its targets have not been investigated. To explore this possibility, we measured olfactory discrimination, olfactory bulb volume, primary olfactory cortex and basal ganglia volume in patients who had SARS-CoV-2 infection more than 12 weeks previously, who were then divided into COVID and long-COVID groups on the basis of selfreported fatigue and concentration complaints. Method(s): This cross-sectional study included 25 post-infection and 19 demographically-matched, no-COVID control participants, we investigated effects on olfaction using NIH Toolbox Odor Identification Test and the Monell Smell Questionnaire. GM structure was assessed with voxel-based morphometry and manual delineation of high resolution (1mm3), T1- and T2-weighted MRI data. Linear regression was used to model group effects on GM structure, adjusting for age, sex, education and total intracranial volume. CAT12/SPM12 and R were used for image processing and statistical modeling. Result(s): Results. The NIH Toolbox Odor Identification Test failed to show differences among the groups. In contrast, the Monell Smell Questionnaire revealed persistently diminished and distorted smell in 50% of the long-COVID sample. Olfactory bulb volume was lower in the long-COVID group (p=0.02). Primary olfactory cortex volume was reduced in the long-COVID group (p=0.004). Caudate volume was also lower in the long-COVID group (p=0.04). Conclusion(s): Conclusions. In the absence of olfactory discrimination problems, long-COVID, but not COVID, patients experience persistent olfactory loss and distortion. These perceptual problems are associated with lower olfactory bulb, primary olfactory cortex, and caudate volume, suggesting that the effects of SARS-CoV-2 infection can extend beyond the olfactory periphery in some cases to affect central targets. (Figure Presented).

THE NERVOUS SYSTEM, ANOTHER VICTIM OF SARS-COV-2

COVID-19 is the name of sickness headed by SARS-CoV-2, which gated the confinement restrictions since March 2020. At the beginning the S protein was identified as the "key" that enhances entering human body, due to its affinity with ACE2 receptor. ACE2 receptor is known to be expressed in a variety of tissues in a manner in which that location increases their infection-probabilities in exposure to this virus. The brain contains two regions where ACE2 is manly expressed: 1) The olfactory bulb which is thought to be involved in loss of smell and facilitating entering to the Central Nervous System, on the other hand 2) the brainstem keeps imbibed the Pre-Botzinger complex, a mediator of respiratory rhythm, showed its implications in oxygen depletion because of abnormal working of O2, and CO2 sensing chemoreceptors. In concern with PNS it is considered virus-nociceptors interaction as the most likely reason to muscular pain and headache. © 2022 Harvard University Law School. All rights reserved.

[The alleged mechanisms of olfactory disorders in the new coronavirus infection]. / Vozmozhnye mekhanizmy narushenii obonyaniya pri novoi koronavirusnoi infektsii.

In March 2020, the World Health Organization (WHO) announced the beginning of the COVID-19 pandemic, which continues to the present. A change in the sense of smell, up to the complete disappearance of odors, is regarded as one of the early symptoms of the disease. Sometimes anosmia was the only sign of infection of the patient. As is known, a disturbance of the sense of smell indicates a serious pathology of the brain, such as the consequences of traumatic brain injuries, strokes, Alzheimer's disease, Parkinson's disease, autoimmune diseases, a side-effect of drug therapy. The review is dedicated to the pathogenesis of anosmia in COVID-19. For a better understanding of the pathogenesis, the article presents a brief anatomy and physiology of the olfactory organ as well as the probable mechanisms of anosmia: encephalitis, inflammatory edema of the olfactory cleft, olfactory epithelium damage, apoptosis of bipolar neurons, damage of olfactory cell cilia and damage of olfactory bulbs. Because of the rapid accumulation of information on this topic, there is a need to structure, periodic systematization and presentation to a wide range of specialists.

Clinical and Imaging Evaluation of COVID-19-Related Olfactory Dysfunction.

BACKGROUND: Olfactory dysfunction has been reported in 47.85% of COVID patients. It can be broadly categorized into conductive or sensorineural olfactory loss. Conductive loss occurs due to impaired nasal air flow, while sensorineural loss implies dysfunction of the olfactory epithelium or central olfactory pathways. OBJECTIVES: The aim of this study was to analyze the clinical and imaging findings in patients with COVID-related olfactory dysfunction. Additionally, the study aimed to investigate the possible mechanisms of COVID-related olfactory dysfunction. METHODS: The study included 110 patients with post-COVID-19 olfactory dysfunction, and a control group of 50 COVID-negative subjects with normal olfactory function. Endoscopic nasal examination was performed for all participants with special focus on the olfactory cleft. Smell testing was performed for all participants by using a smell diskettes test. Olfactory pathway magnetic resonance imaging (MRI) was done to assess the condition of the olfactory cleft and the dimensions and volume of the olfactory bulb. RESULTS: Olfactory dysfunction was not associated with nasal symptoms in 51.8% of patients. MRI showed significantly increased olfactory bulb dimensions and volume competed to controls. Additionally, it revealed olfactory cleft edema in 57.3% of patients. On the other hand, radiological evidence of sinusitis was detected in only 15.5% of patients. CONCLUSION: The average olfactory bulb volumes were significantly higher in the patients' group compared to the control group, indicating significant edema and swelling in the olfactory bulb in patients with COVID-related olfactory dysfunction. Furthermore, in most patients, no sinonasal symptoms such as nasal congestion or rhinorrhea were reported, and similarly, no radiological evidence of sinusitis was detected. Consequently, the most probable mechanism of COVID-related olfactory dysfunction is sensorineural loss through virus spread and damage to the olfactory epithelium and pathways.

Neurological Manifestations In COVID-19 Patients: An Imaging Review

Background: The COVID-19 pandemic that started in late 2019, has posed a great health challenge to India rapidly elevating our country to the second most affected nation after the United States. While the respiratory manifestations of COVID-19 are widely-known, there is paucity of information on its neurological manifestations in Indian literature. The imaging features of the diverse neurological presentations such as stroke, encephalitis, demyelination, hemorrhages and vascular involvement are reviewed in this article. Objective of the review is to discuss the spectrum of neuroimaging features in COVID-19. Method(s): Multiple publications from systematic and cohort studies on neuroimaging are reviewed in this article. Due permission was obtained from the publishers to reproduce the illustrations because of lack of adequate neuroimaging data in our country. Result(s): Ischemic infarcts, micro-hemorrhages, parenchymal hematomas and white matter changes, both diffuse and focal were the most common manifestations. Acute necrotizing hemorrhagic encephalitis, features resembling posterior reversible encephalopathy syndrome (PRES) and acute demyelinating encephalomyelitis (ADEM), arterial dissections, dural sinus and deep venous thrombosis were reported. Olfactory bulb and white matter signal ratios were elevated in anosmic patients. Micro-structural changes such as remyelination and neurogenesis indicated processes of repair. Conclusion(s): Ischemic and hemorrhagic lesions are the most common neuroimaging abnormalities in COVID-19 patients, though 40% of the studies are normal. Awareness of the imaging features is essential for management of these patients in the current pandemic. Severity of illness and risk of spread of infection are major constraints for neuroimaging. Copyright © 2022 International Medical Sciences Academy. All rights reserved.

Olfactory system measurements in COVID-19: a systematic review and meta-analysis.

PURPOSE: The neurotropism of SARS-CoV-2 and the consequential damage to the olfactory system have been proposed as one of the possible underlying causes of olfactory dysfunction in COVID-19. We aimed to aggregate the results of the studies which reported imaging of the olfactory system of patients with COVID-19 versus controls. METHODS: PubMed and EMBASE were searched to identify relevant literature reporting the structural imaging characteristics of the olfactory bulb (OB), olfactory cleft, olfactory sulcus (OS), or olfactory tract in COVID-19 patients. Hedge's g and weighted mean difference were used as a measure of effect size. Quality assessment, subgroup analyses, meta-regression, and sensitivity analysis were also conducted. RESULTS: Ten studies were included in the qualitative synthesis, out of which seven studies with 183 cases with COVID-19 and 308 controls without COVID-19 were enrolled in the quantitative synthesis. No significant differences were detected in analyses of right OB volume and left OB volume. Likewise, right OS depth and left OS depth were also not significantly different in COVID-19 cases compared to non-COVID-19 controls. Also, we performed subgroup analysis, meta-regression, and sensitivity analysis to investigate the potential effect of confounding moderators. CONCLUSION: The findings of this review did not confirm alterations in structural imaging of the olfactory system, including OB volume and OS depth by Covid-19 which is consistent with the results of recent histopathological evaluations.

Effects of nasal inflammation on the olfactory bulb.

Sinonasal diseases, such as rhinosinusitis, affect up to 12% of individuals each year which constitutes these diseases as some of the most common medical conditions in the world. Exposure to environmental pathogens and toxicants via the nasal cavity can result in a severe inflammatory state commonly observed in these conditions. It is well understood that the epithelial and neuronal cells lining the olfactory mucosa, including olfactory sensory neurons (OSNs), are significantly damaged in these diseases. Prolonged inflammation of the nasal cavity may also lead to hyposmia or anosmia. Although various environmental agents induce inflammation in different ways via distinct cellular and molecular interactions, nasal inflammation has similar consequences on the structure and homeostatic function of the olfactory bulb (OB) which is the first relay center for olfactory information in the brain. Atrophy of the OB occurs via thinning of the superficial OB layers including the olfactory nerve layer, glomerular layer, and superficial external plexiform layer. Intrabulbar circuits of the OB which include connectivity between OB projection neurons, OSNs, and interneurons become significantly dysregulated in which synaptic pruning and dendritic retraction take place. Furthermore, glial cells and other immune cells become hyperactivated and induce a state of inflammation in the OB which results in upregulated cytokine production. Moreover, many of these features of nasal inflammation are present in the case of SARS-CoV-2 infection. This review summarizes the impact of nasal inflammation on the morphological and physiological features of the rodent OB.

Scent of stem cells: How can neurogenesis make us smell better?

Throughout the animal kingdom, olfaction underlies the ability to perceive chemicals in the environment as a fundamental adaptation with a plethora of functions. Unique among senses, olfaction is characterized by the integration of adult born neurons at the level of both the peripheral and central nervous systems. In fact, over the course of life, Neural Stem Cells (NSCs) reside within the peripheral Olfactory Epithelium (OE) and the brain's subventricular zone that generate Olfactory Sensory Neurons (OSNs) and interneurons of the Olfactory Bulb (OB), respectively. Despite this unique hallmark, the role(s) of adult neurogenesis in olfactory function remains elusive. Notably, while the molecular signature and lineage of both peripheral and central NSC are being described with increasing detail and resolution, conflicting evidence about the role of adult born neurons in olfactory sensitivity, discrimination and memory remains. With a currently increasing prevalence in olfactory dysfunctions due to aging populations and infections such as COVID-19, these limited and partly controversial reports highlight the need of a better understanding and more systematic study of this fascinating sensory system. Specifically, here we will address three fundamental questions: What is the role of peripheral adult neurogenesis in sustaining olfactory sensitivity? How can newborn neurons in the brain promote olfactory discrimination and/or memory? And what can we learn from fundamental studies on the biology of olfaction that can be used in the clinical treatment of olfactory dysfunctions?

Anatomical barriers against SARS-CoV-2 neuroinvasion at vulnerable interfaces visualized in deceased COVID-19 patients.

Can SARS-CoV-2 hitchhike on the olfactory projection and take a direct and short route from the nose into the brain? We reasoned that the neurotropic or neuroinvasive capacity of the virus, if it exists, should be most easily detectable in individuals who died in an acute phase of the infection. Here, we applied a postmortem bedside surgical procedure for the rapid procurement of tissue, blood, and cerebrospinal fluid samples from deceased COVID-19 patients infected with the Delta, Omicron BA.1, or Omicron BA.2 variants. Confocal imaging of sections stained with fluorescence RNAscope and immunohistochemistry afforded the light-microscopic visualization of extracellular SARS-CoV-2 virions in tissues. We failed to find evidence for viral invasion of the parenchyma of the olfactory bulb and the frontal lobe of the brain. Instead, we identified anatomical barriers at vulnerable interfaces, exemplified by perineurial olfactory nerve fibroblasts enwrapping olfactory axon fascicles in the lamina propria of the olfactory mucosa.

A singular case of hyposmia and transient audiovestibular post-vaccine disorders: case report and literature review.

Introduction: Rare and mild adverse effects on cranial nerves have been reported after vaccination. Here, we report a singular case of smell and taste disorder associated with tinnitus that occurred after Oxford-AstraZeneca vaccination together with a review of the available literature. Case presentation: A 76-year-old patient experienced smell disorder, ear fullness and tinnitus 2 days after the first dose of Oxford-AstraZeneca vaccine. The patient then underwent a complete audiological and Ear, Nose and Throat evaluation, nasal endoscopy, Sniffin'Sticks battery, audiometric test battery, and cerebral magnetic resonance imaging (MRI). The exams revealed hyposmia and bilateral reduction of the volume of the olfactory bulbs (OB). At the follow-up, tinnitus was completely resolved while olfactory dysfunction only partially reduced. Review of the literature: A PubMed search was conducted on olfactory and gustatory dysfunctions after COVID-19 vaccination resulting in four case reports with a total of 10 patients. The main symptoms were hyposmia, parosmia, and dysgeusia developed after 1-9 days from vaccination with complete resolution occurring within 1 month. Notably, none of the considered articles reported reduction of OB volumes at cerebral MRI. Discussion: So far, no definitive cause-effect relationship has been established between anti-COVID19 vaccination and otolaryngologic adverse reactions. The persistence of hyposmia in our patient could possibly be explained by the reduction in OB volume, even though also the advanced age of the patient needs to be taken into account. This is a first indication of a cause-effect relation between hyposmia and Covid19 vaccination, even though a more robust study is needed to confirm the autoimmunological mechanisms responsible for these rare adverse reactions. However, it is worth highlighting that benefits of the anti-COVID-19 vaccination clearly outweigh the risk of rare adverse events.

Efficacy, Safety, and Tolerability of PH94B in Adjustment Disorder With Anxiety: Design of an Exploratory Phase 2A Clinical Trial

BACKGROUND: Adjustment disorders are now primary diagnoses in the trauma and stressrelated disorders section of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). Adjustment disorder with anxiety (AjDA) is the development of emotional or behavioral symptoms considered excessive in response to stressful events, significantly impairing a person's ability to function in social, occupational, and/ or other situations. Traumatic experiences related to the COVID-19 pandemic may have increased rates of adjustment disorders, especially among those whose life routines were disrupted by pandemic-associated stress and anxiety. PH94B (3b-hydroxy-androsta-4,16-dien-ol) has shown rapid-onset efficacy in the treatment of social anxiety disorder (Liebowitz et al. Am J Psychiatry. 2014). PH94B is a neuroactive steroid administered as a nasal spray that engages olfactory chemosensory neurons, activating subsets of olfactory bulb neurons that project directly to the limbic amygdala regulating fear and anxiety circuits. OBJECTIVE: To assess the efficacy, safety, and tolerability of PH94B in adults with AjDA. METHODS: This is an exploratory, phase 2A, randomized, double-blind, 4-week, placebo-controlled, 2-arm study in adults with AjDA. The primary outcome is change from baseline to week 4 in the Hamilton Anxiety Rating Scale (HAM-A) total score after intranasal administration of PH49B 4 times daily vs placebo. Patients with a DSM-5 diagnosis of AjDA confirmed by the Mini-International Neuropsychiatric Interview (MINI) with Adjustment Disorders Module and a clinician-rated HAM-A score of ≥20 at screening (Visit 1), with ≤15% decrease at baseline (Visit 2, randomization) are eligible for inclusion. Secondary outcomes include change from baseline to week 4 in the Adjustment Disorder New Module Scale (ADNM), the International Adjustment Disorder Questionnaire (IADQ), the Clinical Global Impression of Improvement (CGI-I), and the Patient Global Impression of Change (PGI-C). Change from baseline in the Hamilton Depression Rating Scale (HAM-D) was exploratory. RESULTS: A total of 40 patients will be randomized (1:1 drug to placebo). The study design features the use of the ADNM and IADQ, newly developed according to ICD-11 criteria for evaluation of AjDA. While both are validated, neither has been tested in placebo-controlled clinical trials. Both scales begin with a list of stressors (18 for ADNM and 9 for IADQ);a yes answer to any 1 stressor triggers a series of questions about the frequency and duration of a patient's reaction to the stressor (ADNM) or quantifies symptoms in response to the stressor (IADQ). CONCLUSIONS: Anxiety disorders are the most prevalent psychiatric disorders and a leading cause of disability. Anxiety and impaired functioning are increasing, particularly in response to the COVID-19 pandemic, and no pharmacologic treatment is currently approved by the FDA for AjDA. PH94B, an investigational pherine nasal spray, is also being studied for treatment of other anxiety-related disorders.

In vitro and in vivo differences in neurovirulence between D614G, Delta And Omicron BA.1 SARS-CoV-2 variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with various neurological complications. Although the mechanism is not fully understood, several studies have shown that neuroinflammation occurs in the acute and post-acute phase. As these studies have predominantly been performed with isolates from 2020, it is unknown if there are differences among SARS-CoV-2 variants in their ability to cause neuroinflammation. Here, we compared the neuroinvasiveness, neurotropism and neurovirulence of the SARS-CoV-2 ancestral strain D614G, the Delta (B.1.617.2) and Omicron BA.1 (B.1.1.529) variants using in vitro and in vivo models. The Omicron BA.1 variant showed reduced neurotropism and neurovirulence compared to Delta and D614G in human induced pluripotent stem cell (hiPSC)-derived cortical neurons co-cultured with astrocytes. Similar differences were obtained in Syrian hamsters inoculated with D614G, Delta and the Omicron BA.1 variant 5 days post infection. Replication in the olfactory mucosa was observed in all hamsters, but most prominently in D614G inoculated hamsters. Furthermore, neuroinvasion into the CNS via the olfactory nerve was observed in D614G, but not Delta or Omicron BA.1 inoculated hamsters. Furthermore, neuroinvasion was associated with neuroinflammation in the olfactory bulb of hamsters inoculated with D614G. Altogether, our findings suggest differences in the neuroinvasive, neurotropic and neurovirulent potential between SARS-CoV-2 variants using in vitro hiPSC-derived neural cultures and in vivo in hamsters during the acute phase of the infection.

Oral SARS-CoV-2 Inoculation Causes Nasal Viral Infection Leading to Olfactory Bulb Infection: An Experimental Study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can cause long-lasting anosmia, but the impact of SARS-CoV-2 infection, which can spread to the nasal cavity via the oral route, on the olfactory receptor neuron (ORN) lineage and olfactory bulb (OB) remains undetermined. Using Syrian hamsters, we explored whether oral SARS-CoV-2 inoculation can lead to nasal viral infection, examined how SARS-CoV-2 affects the ORN lineage by site, and investigated whether SARS-CoV-2 infection can spread to the OB and induce inflammation. On post-inoculation day 7, SARS-CoV-2 presence was confirmed in the lateral area (OCAM-positive) but not the nasal septum of NQO1-positive and OCAM-positive areas. The virus was observed partially infiltrating the olfactory epithelium, and ORN progenitor cells, immature ORNs, and mature ORNs were fewer than in controls. The virus was found in the olfactory nerve bundles to the OB, suggesting the nasal cavity as a route for SARS-CoV-2 brain infection. We demonstrated that transoral SARS-CoV-2 infection can spread from the nasal cavity to the central nervous system and the possibility of central olfactory dysfunction due to SARS-CoV-2 infection. The virus was localized at the infection site and could damage all ORN-lineage cells.

Parkinson's disease induced by SARSCoV2

Background and aims: COVID-19 infections are reported in numerous case-reports as a trigger for development of Parkinson's disease (PD). We report 4 patients with symptoms of PD developed or exagerated after SARSCoV2 infection. Methods: Patients were retrospectively recruited in an outpatient clinic of Department of Neurology, Faculty of Health Science, Medical University of Warsaw. Patients were independently assessed by 2 neurologists experienced in movement disorders. Results: We identified 4 patients with rapid onset of PD symptoms following COVID-19. All patients were female. Symptoms of COVID-19 included headache in 4/4 cases and anosmia in 3/4 cases. PCR test confirmed SARS-CoV2 infection in all cases. The age of onset was between 28 and 62 years old. The rest tremor was present in all patients, ridgidity in 3/4 patients. Non-motor symptoms included RBD in 2/4 patients. Two patients were treated with levodopa with good response. MRI findings were nonsignificant. The SPECT-DatScan was performed in one patient and was typical for parkinsonian disorders. The positive family history was present in two patients. Conclusion: We conclude that COVID-19 may trigger development of parkinsonian motor symptoms or exaggerate the slight disease progression. The cause is unknown. Involvement of olfactory bulb could trigger neuroinflammation in line with Braak's hypothesis. COVID-19 may also induce parkinsonism in patients with genetic predisposition.

Evaluation of the sense of smell and taste in patients with Neurofibromatosis Type 1

Objective The objective of this study was to determine if patients with Neurofibromatosis Type 1 (NF1) have an impaired sense of smell or taste. Neurofibromin, the NF1gene protein product is ubiquitous in the body and is especially associated with the development of neurogenetic structures. Lately enlarged olfactory bulbs have been described in patients with NF1. Until now, there is no study to evaluate the sense of smell and taste in patients with NF1. Method This study has been approved by the Hamburg Ethics committee. An evaluation of the sense of smell and taste was undertaken in 26 patients with NF1 using the Burghart Sniffin' Sticks. Three patients were excluded due to a prior infection with the Corona virus. As a control group the same examination was performed in healthy individuals (same sex/ same age as the NF1 patients) by the same examiner. Results Preliminary results show a normal sense of smell in patients with NF1. The morphologic finding of enlarged olfactory bulbs seem to have no functional equivalent. However, 8 out of 23 patients with NF1 had difficulties identifying at least one taste flavor. The data collection of the control group is still ongoing, thus far none of the study participants misidentified a taste flavor. A statistical significance is aimed at by increasing the case numbers.

COVID-19 and olfactory dysfunction: a looming wave of dementia?

Olfactory dysfunction is a hallmark symptom of COVID-19 disease resulting from the SARS-CoV-2 virus. The cause of the sudden and usually temporary anosmia that most people suffer from COVID-19 is likely entirely peripheral-inflammation and other damage caused by the virus in the sensory epithelium inside the upper recesses of the nasal cavity can damage or prevent chemicals from properly activating the olfactory sensory neurons. However, persistent olfactory dysfunction from COVID-19, in the form of hyposmia and parosmia (decreased or altered smell) may affect as many as 15 million people worldwide. This epidemic of olfactory dysfunction is thus a continuing public health concern. Mounting evidence suggests that the SARS-CoV-2 virus itself or inflammation from the immune response in the nasal sensory epithelium may invade the olfactory bulb, likely via non-neuronal transmission. COVID-19-related long-term olfactory dysfunction and early damage to olfactory and limbic brain regions suggest a pattern of degeneration similar to that seen in early stages of Alzheimer's disease, Parkinson's disease, and Lewy body dementia. Thus, long-term olfactory dysfunction coupled with cognitive and emotional disturbance from COVID-19 may be the first signs of delayed onset dementia from neurodegeneration. Few treatments are known to be effective to prevent further degeneration, but the first line of defense against degeneration may be olfactory and environmental enrichment. There is a pressing need for more research on treatments for olfactory dysfunction and longitudinal studies including cognitive and olfactory function from patients who have recovered from even mild COVID-19.NEW & NOTEWORTHY More than 15 million people worldwide experience persistent COVID-19 olfactory dysfunction, possibly caused by olfactory bulb damage. SARS-CoV-2 can cause inflammation and viral invasion of the olfactory bulb, initiating a cascade of degeneration similar to Alzheimer's disease and Lewy body disease. People who have had even mild cases of COVID-19 show signs of degeneration in cortical areas connected with the olfactory system. These data suggest a wave of post-COVID dementia in the coming decades.