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Journal of the Neurological Sciences Jun 2021Olfaction, one of our five main qualitative sensory abilities, is the action of smelling or the capacity to smell. Olfactory impairment can be a sign of a medical... (Review)
Review
Olfaction, one of our five main qualitative sensory abilities, is the action of smelling or the capacity to smell. Olfactory impairment can be a sign of a medical problem, from a benign nasal/sinus problem up to a potentially serious brain injury. However, although clinicians (neurologists or not) usually test the olfactory nerves in specific clinical situations (for example, when a neurodegenerative disorder is suspected), they may omit such tests in many other situations. With the recent COVID-19 pandemic, the resurgence of anosmia has reminded us of the importance of testing this sensorineural function. We retrace here the main historical steps and discoveries concerning olfaction and anosmia.
Topics: Anosmia; COVID-19; Humans; Olfaction Disorders; Pandemics; SARS-CoV-2; Smell
PubMed: 33848701
DOI: 10.1016/j.jns.2021.117433 -
Tropical Biomedicine Sep 2021Ever since the first reported case series on SARS-CoV-2-induced neurological manifestation in Wuhan, China in April 2020, various studies reporting similar as well as... (Review)
Review
Ever since the first reported case series on SARS-CoV-2-induced neurological manifestation in Wuhan, China in April 2020, various studies reporting similar as well as diverse symptoms of COVID-19 infection relating to the nervous system were published. Since then, scientists started to uncover the mechanism as well as pathophysiological impacts it has on the current understanding of the disease. SARS-CoV-2 binds to the ACE2 receptor which is present in certain parts of the body which are responsible for regulating blood pressure and inflammation in a healthy system. Presence of the receptor in the nasal and oral cavity, brain, and blood allows entry of the virus into the body and cause neurological complications. The peripheral and central nervous system could also be invaded directly in the neurogenic or hematogenous pathways, or indirectly through overstimulation of the immune system by cytokines which may lead to autoimmune diseases. Other neurological implications such as hypoxia, anosmia, dysgeusia, meningitis, encephalitis, and seizures are important symptoms presented clinically in COVID-19 patients with or without the common symptoms of the disease. Further, patients with higher severity of the SARS-CoV-2 infection are also at risk of retaining some neurological complications in the long-run. Treatment of such severe hyperinflammatory conditions will also be discussed, as well as the risks they may pose to the progression of the disease. For this review, articles pertaining information on the neurological manifestation of SARS-CoV-2 infection were gathered from PubMed and Google Scholar using the search keywords "SARS-CoV-2", "COVID-19", and "neurological dysfunction". The findings of the search were filtered, and relevant information were included.
Topics: Angiotensin-Converting Enzyme 2; Anosmia; COVID-19; Central Nervous System; Dysgeusia; Encephalitis, Viral; Humans; Meningitis, Viral; Nervous System Diseases; Peripheral Nervous System; SARS-CoV-2; Seizures
PubMed: 34608117
DOI: 10.47665/tb.38.3.086 -
Headache Sep 2020To summarize for the trainee audience the possible mechanisms of headache in patients with COVID-19 as well as to outline the impact of the pandemic on patients with... (Review)
Review
OBJECTIVE
To summarize for the trainee audience the possible mechanisms of headache in patients with COVID-19 as well as to outline the impact of the pandemic on patients with headache disorders and headache medicine in clinical practice.
BACKGROUND
COVID-19 is a global pandemic caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2, of which a large subset of patients features neurological symptoms, commonly headache. The virus is highly contagious and is, therefore, changing clinical practice by forcing limitations on in-person visits and procedural treatments, more quickly shifting toward the widespread adaptation of telemedicine services.
DESIGN/RESULTS
We review what is currently known about the pathophysiology of COVID-19 and how it relates to possible mechanisms of headache, including indirect, potential direct, and secondary causes. Alternative options for the treatment of patients with headache disorders and the use of telemedicine are also explored.
CONCLUSIONS
Limited information exists regarding the mechanisms and timing of headache in patients with COVID-19, though causes relate to plausible direct viral invasion of the nervous system as well as the cytokine release syndrome. Though headache care in the COVID-19 era requires alterations, the improved preventive treatment options now available and evidence for feasibility and safety of telemedicine well positions clinicians to take care of such patients, especially in the COVID-19 epicenter of New York City.
Topics: Aged, 80 and over; Anosmia; COVID-19; Comorbidity; Cytokine Release Syndrome; Education, Medical, Continuing; Headache; Headache Disorders, Secondary; Humans; Inflammation Mediators; Leukoencephalitis, Acute Hemorrhagic; Migraine Disorders; Neurology; New York City; Pandemics; Physical Distancing; SARS-CoV-2; Telemedicine
PubMed: 32521039
DOI: 10.1111/head.13884 -
Otolaryngology--head and Neck Surgery :... Dec 2023Olfactory disorders are well-studied in the adult population, however, there is a paucity of literature characterizing olfactory dysfunction in pediatric patients. The... (Review)
Review
OBJECTIVE
Olfactory disorders are well-studied in the adult population, however, there is a paucity of literature characterizing olfactory dysfunction in pediatric patients. The purpose of this scoping review was to identify known causes of olfactory loss in pediatric populations, clarify the extent of use and validity of smell tests, and summarize current therapies for olfactory loss.
DATA SOURCES
PubMed, Ovid MEDLINE, and Web of Science.
REVIEW METHODS
Databases were systematically searched in September 2020. Two independent reviewers conducted the title and abstract screen, followed by review of full-texts for inclusion based on preset inclusion and exclusion criteria. Extracted data included study type, age/age-range of participants, gender, radiological evidence of olfactory dysfunction, types and results of smell tests used, etiology of olfactory loss, and therapies employed for olfactory loss.
RESULTS
A total of 103 articles (n = 1654) were eligible for final data extraction. The University of Pennsylvania Smell Identification Test was used most frequently for smell testing (21% of studies). In total, 45 causes of olfactory dysfunction have been elucidated by this study: 22 congenital and 23 acquired. Few therapies were described, and all were specific to the etiology of olfactory loss.
CONCLUSION
Olfactory dysfunction has a wide range of etiologies in the pediatric population, and clinicians should have a diagnostic algorithm for how to identify a cause should they encounter it in practice. If no etiology can be identified, education around safety should be provided to both the patient and their caregivers.
Topics: Adult; Humans; Child; Smell; Olfaction Disorders; Anosmia
PubMed: 37449420
DOI: 10.1002/ohn.415 -
The Cochrane Database of Systematic... Sep 2022Olfactory dysfunction is a common consequence of COVID-19 infection and persistent symptoms can have a profound impact on quality of life. At present there is little... (Review)
Review
BACKGROUND
Olfactory dysfunction is a common consequence of COVID-19 infection and persistent symptoms can have a profound impact on quality of life. At present there is little guidance on how best to treat this condition. A variety of interventions have been suggested to promote recovery, including medication and olfactory training. However, it is uncertain whether any intervention is of benefit. This is an update of the 2021 review with one additional study added. OBJECTIVES: 1) To evaluate the benefits and harms of any intervention versus no treatment for people with persisting olfactory dysfunction due to COVID-19 infection. 2) To keep the evidence up-to-date, using a living systematic review approach. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the latest search was 20 October 2021. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in people with COVID-19 related olfactory disturbance that had persisted for at least four weeks. We included any intervention compared to no treatment or placebo. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were the recovery of sense of smell, disease-related quality of life and serious adverse effects. Secondary outcomes were the change in sense of smell, general quality of life, prevalence of parosmia and other adverse effects (including nosebleeds/bloody discharge). We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included two studies with 30 participants. The studies evaluated the following interventions: systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant and palmitoylethanolamide plus luteolin. Systemic corticosteroids plus intranasal corticosteroid/mucolytic/decongestant compared to no intervention We included a single RCT with 18 participants who had anosmia for at least 30 days following COVID-19 infection. Participants received a 15-day course of oral corticosteroids combined with nasal irrigation (consisting of an intranasal corticosteroid/mucolytic/decongestant solution) or no intervention. Psychophysical testing was used to assess olfactory function at 40 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results. Palmitoylethanolamide plus luteolin compared to no intervention We included a single RCT with 12 participants who had anosmia or hyposmia for at least 90 days following COVID-19 infection. Participants received a 30-day course of palmitoylethanolamide and luteolin or no intervention. Psychophysical testing was used to assess olfactory function at 30 days. This is a single, small study and for all outcomes the certainty of evidence was very low. We are unable to draw meaningful conclusions from the numerical results.
AUTHORS' CONCLUSIONS
There is very limited evidence available on the efficacy and harms of treatments for persistent olfactory dysfunction following COVID-19 infection. However, we have identified a number of ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available.
Topics: Adrenal Cortex Hormones; Anosmia; COVID-19; Expectorants; Humans; Luteolin; Nasal Decongestants; Randomized Controlled Trials as Topic; Smell
PubMed: 36062970
DOI: 10.1002/14651858.CD013876.pub3 -
American Journal of Rhinology & Allergy Nov 2021Anosmia and ageusia are symptoms commonly associated with COVID-19, but the relationship with disease severity, onset and recovery are unclear.
BACKGROUND
Anosmia and ageusia are symptoms commonly associated with COVID-19, but the relationship with disease severity, onset and recovery are unclear.
OBJECTIVE
To examine factors associated with anosmia and ageusia and the recovery from these symptoms in an ethnically diverse cohort.
METHODS
Individuals tested for SARS-CoV-2 between March and April 2020 were eligible for the study. Randomly selected participants answered a telephone questionnaire on COVID-19 symptoms with a focus on anosmia and ageusia. Additionally, relevant past medical history and data on the COVID-19 clinical course were obtained from electronic medical records. 486 patients were in the COVID-19 group and 103 were COVID-19-negative.
RESULTS
Patients who were younger were more likely to report anosmia and/or ageusia (odds ratio (OR) for anosmia per 1-year increase in age: 0·98, 95%CI:0-97-0·99, = 0·003; for ageusia: 0·98, 95%CI:0·97-0·99, = 0·005) as were patients with lower eosinophil counts (OR for anosmia per 0.1-K/μL increase in eosinophils: 0·02, 95%CI:0·001-0·46, = 0·01, for ageusia 0·10, 95%CI:0·01-0·97, = 0·047). Male gender was independently associated with a lower probability of ageusia (OR:0·56, 95%CI:0·38-0·82, = 0·003) and earlier sense of taste recovery (HR:1·44, 95%CI:1·05-1·98, = 0·02). Latinos showed earlier sense of taste recovery than white patients (HR:1·82, 95%CI:1·05-3·18, = 0·03).
CONCLUSION
Anosmia and ageusia were more common among younger patients and those with lower blood eosinophil counts. Ageusia was less commonly reported among men, and time to taste recovery was earlier among both men and Latinos.
Topics: Ageusia; Anosmia; COVID-19; Eosinophils; Humans; Infant; Male; Olfaction Disorders; SARS-CoV-2
PubMed: 33813917
DOI: 10.1177/19458924211004800 -
American Journal of Rhinology & Allergy Mar 2023Chronic rhinosinusitis (CRS) is the leading cause of olfactory dysfunction in the general population. Olfactory dysfunction is more common in patients with CRS with... (Review)
Review
BACKGROUND
Chronic rhinosinusitis (CRS) is the leading cause of olfactory dysfunction in the general population. Olfactory dysfunction is more common in patients with CRS with nasal polyposis (CRSwNP) compared to those without polyps.
PURPOSE
The present review aims to summarize the current literature on the mechanism behind olfactory dysfunction in CRSwNP and the impact of therapy on olfactory outcomes in this patient population.
METHODS
A comprehensive review of the available literature on olfaction in CRSwNP was performed. We evaluated the most recent evidence from studies on the mechanisms behind smell loss in CRSwNP and the impact of medical and surgical therapy for CRS on olfactory outcomes.
RESULTS
The mechanism behind olfactory dysfunction in CRSwNP is not completely understood, but evidence from clinical research and animal models suggests both an obstructive component causing conductive olfactory loss and an inflammatory response in the olfactory cleft leading to sensorineural olfactory loss. Oral steroids and endoscopic sinus surgery have both shown efficacy in improving olfactory outcomes in CRSwNP in the short term; however, the long-term response of these treatments remains uncertain. Newer targeted biologic therapies, such as dupilumab, have also shown remarkable and durable improvement in smell loss for CRSwNP patients.
CONCLUSION
Olfactory dysfunction is highly prevalent in the CRSwNP population. Although significant advances have been made in our understanding of olfactory dysfunction in the setting of CRS, additional studies are needed to elucidate cellular and molecular changes mediated by type 2-mediated inflammation in the olfactory epithelium with potential downstream effects on the central olfactory system. Further identification of these underlying basic mechanisms will be vital for developing future therapies targeted to improve olfactory dysfunction in patients with CRSwNP.
Topics: Humans; Animals; Smell; Anosmia; Inflammation; Models, Animal; Nasal Polyps
PubMed: 36848279
DOI: 10.1177/19458924231153485 -
CMAJ : Canadian Medical Association... Feb 2021
Observational Study
Topics: Adolescent; Alberta; Anosmia; Asymptomatic Infections; COVID-19; COVID-19 Testing; Child; Child, Preschool; Female; Fever; Headache; Humans; Infant; Infant, Newborn; Male; Nausea; Vomiting
PubMed: 33526549
DOI: 10.1503/cmaj.202065-f -
Praxis 2021
Topics: Administration, Intranasal; Anosmia; COVID-19; Humans; SARS-CoV-2; Steroids
PubMed: 34019445
DOI: 10.1024/1661-8157/a003673 -
Journal of Neuroinflammation Dec 2023The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimer's...
BACKGROUND
The neurological effects of the coronavirus disease of 2019 (COVID-19) raise concerns about potential long-term consequences, such as an increased risk of Alzheimer's disease (AD). Neuroinflammation and other AD-associated pathologies are also suggested to increase the risk of serious SARS-CoV-2 infection. Anosmia is a common neurological symptom reported in COVID-19 and in early AD. The olfactory mucosa (OM) is important for the perception of smell and a proposed site of viral entry to the brain. However, little is known about SARS-CoV-2 infection at the OM of individuals with AD.
METHODS
To address this gap, we established a 3D in vitro model of the OM from primary cells derived from cognitively healthy and AD individuals. We cultured the cells at the air-liquid interface (ALI) to study SARS-CoV-2 infection under controlled experimental conditions. Primary OM cells in ALI expressed angiotensin-converting enzyme 2 (ACE-2), neuropilin-1 (NRP-1), and several other known SARS-CoV-2 receptor and were highly vulnerable to infection. Infection was determined by secreted viral RNA content and confirmed with SARS-CoV-2 nucleocapsid protein (NP) in the infected cells by immunocytochemistry. Differential responses of healthy and AD individuals-derived OM cells to SARS-CoV-2 were determined by RNA sequencing.
RESULTS
Results indicate that cells derived from cognitively healthy donors and individuals with AD do not differ in susceptibility to infection with the wild-type SARS-CoV-2 virus. However, transcriptomic signatures in cells from individuals with AD are highly distinct. Specifically, the cells from AD patients that were infected with the virus showed increased levels of oxidative stress, desensitized inflammation and immune responses, and alterations to genes associated with olfaction. These results imply that individuals with AD may be at a greater risk of experiencing severe outcomes from the infection, potentially driven by pre-existing neuroinflammation.
CONCLUSIONS
The study sheds light on the interplay between AD pathology and SARS-CoV-2 infection. Altered transcriptomic signatures in AD cells may contribute to unique symptoms and a more severe disease course, with a notable involvement of neuroinflammation. Furthermore, the research emphasizes the need for targeted interventions to enhance outcomes for AD patients with viral infection. The study is crucial to better comprehend the relationship between AD, COVID-19, and anosmia. It highlights the importance of ongoing research to develop more effective treatments for those at high risk of severe SARS-CoV-2 infection.
Topics: Humans; SARS-CoV-2; COVID-19; Anosmia; Neuroinflammatory Diseases; Alzheimer Disease; Olfactory Mucosa
PubMed: 38098019
DOI: 10.1186/s12974-023-02979-4