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ACS Chemical Neuroscience Oct 2021The occurrence of anosmia, the loss or change in sense of smell, is one of the most common symptoms of COVID-19 experienced by almost 53% of those affected. Several... (Review)
Review
The occurrence of anosmia, the loss or change in sense of smell, is one of the most common symptoms of COVID-19 experienced by almost 53% of those affected. Several hypotheses explain the mechanism of anosmia in patients suffering from COVID-19. This study aims to review the related mechanisms and answer the questions regarding COVID-19-related anosmia as well as propose a new strategy for treatment of long-term anosmia as a result of COVID-19 infection. This paper covers all of the studies investigating olfactory disorders following COVID-19 infection and explains the possible reasons for the correlated anosmia, including olfactory cleft syndrome, local inflammation in the nasal epithelium, early apoptosis of olfactory cells, changes in olfactory cilia and odor transmission, damage to microglial cells, effect on olfactory bulbs, epithelial olfactory injury, and impairment of olfactory neurons and stem cells. The key questions that arise in this field have been discussed, such as why prevalent anosmia is varied among the age categories and among sexes and the correlation of anosmia with mild or severe COVID-19 infection. The angiotensin-converting enzyme 2 receptor is a significant player in the mechanism of anosmia in COVID-19 patients. Based on current studies, a novel approach to treat long-COVID-19 with ongoing anosmia has been proposed. The fields of smart drug delivery, tissue engineering, and cell therapy provide a hypothesized strategy that can minimize the side effects of current treatments and support efficient recovery of the olfactory system.
Topics: Anosmia; COVID-19; Humans; Olfaction Disorders; SARS-CoV-2; Smell; Post-Acute COVID-19 Syndrome
PubMed: 34609841
DOI: 10.1021/acschemneuro.1c00477 -
Physiological Reviews Oct 2023Anosmia, the loss of the sense of smell, is one of the main neurological manifestations of COVID-19. Although the SARS-CoV-2 virus targets the nasal olfactory... (Review)
Review
Anosmia, the loss of the sense of smell, is one of the main neurological manifestations of COVID-19. Although the SARS-CoV-2 virus targets the nasal olfactory epithelium, current evidence suggests that neuronal infection is extremely rare in both the olfactory periphery and the brain, prompting the need for mechanistic models that can explain the widespread anosmia in COVID-19 patients. Starting from work identifying the non-neuronal cell types that are infected by SARS-CoV-2 in the olfactory system, we review the effects of infection of these supportive cells in the olfactory epithelium and in the brain and posit the downstream mechanisms through which sense of smell is impaired in COVID-19 patients. We propose that indirect mechanisms contribute to altered olfactory system function in COVID-19-associated anosmia, as opposed to neuronal infection or neuroinvasion into the brain. Such indirect mechanisms include tissue damage, inflammatory responses through immune cell infiltration or systemic circulation of cytokines, and downregulation of odorant receptor genes in olfactory sensory neurons in response to local and systemic signals. We also highlight key unresolved questions raised by recent findings.
Topics: Anosmia; Humans; COVID-19; Olfactory Receptor Neurons; Animals; SARS-CoV-2
PubMed: 37342077
DOI: 10.1152/physrev.00012.2023 -
Journal of Neurovirology Apr 2022COVID-19 pandemic spreads worldwide, with more than 100 million positive cases and more than 2 million deaths. From the beginning of the COVID-19 pandemic, several... (Review)
Review
COVID-19 pandemic spreads worldwide, with more than 100 million positive cases and more than 2 million deaths. From the beginning of the COVID-19 pandemic, several otolaryngologists described many cases of a sudden loss of smell (anosmia) associated with the disease with or without additional symptoms. Anosmia is often the first and sometimes the only sign in the asymptomatic carriers of COVID-19. Still, this disorder is underestimated, and it is not life-threatening. However, it significantly decreases the quality of life. This olfactory dysfunction continues in several cases even after the nasopharyngeal swab was negative. The occurrence of anosmia can be used as a screening tool for COVID-19 patients and can be used to identify these patients to accomplish the isolation and tracking procedures. In this review, we highlighted the possible mechanisms of anosmia in COVID-19 patients, major pathologies and features of anosmia, implications of anosmia in early diagnosis of COVID-19, evaluation of the smell function during COVID-19, and management and treatment options of COVID-19 anosmia.
Topics: Anosmia; COVID-19; Humans; Olfaction Disorders; Pandemics; Quality of Life; SARS-CoV-2
PubMed: 35249186
DOI: 10.1007/s13365-022-01060-9 -
Vestnik Otorinolaringologii 2023The article is a systematic review of the literature data summarizes to date on the issue of COVID-19-associated anosmia. We mainly used full-text and abstract... (Review)
Review
The article is a systematic review of the literature data summarizes to date on the issue of COVID-19-associated anosmia. We mainly used full-text and abstract electronic databases (PubMed, Scopus and Web of Science). The paper discusses hypothetical mechanisms of development, clinical features, as well as methods of diagnosis and treatment of COVID-19-associated anosmia.
Topics: Humans; COVID-19; Anosmia; SARS-CoV-2; Olfaction Disorders
PubMed: 37450393
DOI: 10.17116/otorino20228803163 -
Nature Jan 2021The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few months...
The ongoing coronavirus disease 2019 (COVID-19) pandemic is associated with substantial morbidity and mortality. Although much has been learned in the first few months of the pandemic, many features of COVID-19 pathogenesis remain to be determined. For example, anosmia is a common presentation, and many patients with anosmia show no or only minor respiratory symptoms. Studies in animals infected experimentally with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID-19, provide opportunities to study aspects of the disease that are not easily investigated in human patients. Although the severity of COVID-19 ranges from asymptomatic to lethal, most experimental infections provide insights into mild disease. Here, using K18-hACE2 transgenic mice that were originally developed for SARS studies, we show that infection with SARS-CoV-2 causes severe disease in the lung and, in some mice, the brain. Evidence of thrombosis and vasculitis was detected in mice with severe pneumonia. Furthermore, we show that infusion of convalescent plasma from a recovered patient with COVID-19 protected against lethal disease. Mice developed anosmia at early time points after infection. Notably, although pre-treatment with convalescent plasma prevented most signs of clinical disease, it did not prevent anosmia. Thus, K18-hACE2 mice provide a useful model for studying the pathological basis of both mild and lethal COVID-19 and for assessing therapeutic interventions.
Topics: Animals; Anosmia; Brain; COVID-19; Disease Models, Animal; Epithelium; Female; Humans; Immunization, Passive; Inflammation; Lung Diseases; Male; Mice; Paranasal Sinuses; SARS-CoV-2; Treatment Outcome; COVID-19 Serotherapy
PubMed: 33166988
DOI: 10.1038/s41586-020-2943-z -
Alzheimer's & Dementia : the Journal of... Feb 2023Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214...
Olfactory impairment is a potential marker for prodromal dementia, but the underlying mechanisms are poorly understood. This population-based study included 4214 dementia-free participants (age ≥65 years). Olfaction was assessed using the 16-item Sniffin' Sticks identification test. In the subsamples, we measured plasma amyloid beta (Aβ)40, Aβ42, total tau, and neurofilament light chain (NfL; n = 1054); and quantified hippocampal, entorhinal cortex, and white matter hyperintensity (WMH) volumes, and Alzheimer's disease (AD)-signature cortical thickness (n = 917). Data were analyzed with logistic and linear regression models. In the total sample, mild cognitive impairment (MCI) was diagnosed in 1102 persons (26.2%; amnestic MCI, n = 931; non-amnestic MCI, n = 171). Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI. In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness. These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults.
Topics: Humans; Aged; Amyloid beta-Peptides; Anosmia; Brain; Alzheimer Disease; Cognitive Dysfunction; Biomarkers; Aging; tau Proteins
PubMed: 36341691
DOI: 10.1002/alz.12777 -
European Archives of... Jul 2021From the start of the pandemic, many European otolaryngologists observed an unprecendented number of anosmic patients. Early reports proposed that anosmia could be the... (Review)
Review
BACKGROUND
From the start of the pandemic, many European otolaryngologists observed an unprecendented number of anosmic patients. Early reports proposed that anosmia could be the first or even the only symptom of COVID-19 infection, prompting calls for self-isolation in affected patients.
METHODS
In the present article, we review the COVID-19 anosmia literature and try to answer the following two questions: first, why is COVID-19 infection responsible for such a high incidence of anosmia? Second, in patients with more severe forms is anosmia really less prevalent and why?
RESULTS
In terms of the etiology of olfactory dysfunction, several hypotheses were proposed at the outset of the pandemic; that olfactory cleft inflammation and obstruction caused a localized conductive loss, that there was injury to the sustentacular supporting cells in the olfactory epithelium or, given the known neurotropic potential of coronavirus, that the virus could invade and damage the olfactory bulb. Olfactory cleft obstruction may contribute to the olfactory dysfunction in some patients, perhaps most likely in those that show very early resolution, it cannot account for the loss in all patients. Moreover, disordered regrowth and a predominance of immature neurons have been shown to be associated with parosmia, which is a common finding amongst patients with Covid-related anosmia. A central mechanism therefore certainly seems to be consistent with the group of patients with more prolonged olfactory deficits. Sustentacular cells showing ACE-2 immunohistochemical expression 200 to 700 times greater than nasal or tracheal epithelia seem to be the main SARS-CoV-2 gateway. As the pathophysiology of COVID-19 anosmia seems to be better understood, the question of why patients with a moderate to severe form of COVID-19 infection have less olfactory involvement remains unresolved. Different potential explanations are discussed in this review.
CONCLUSIONS
The last 5 months have benefited from great international collaborative research, first highlighting and then proving the value of loss of smell and taste as a symptom of COVID-19. Adoption of loss of smell into the case definition by international public health bodies will facilitate control of disease transmission.
Topics: Anosmia; COVID-19; Humans; Olfaction Disorders; SARS-CoV-2; Smell
PubMed: 32909060
DOI: 10.1007/s00405-020-06285-0 -
Australian Journal of General Practice Apr 2022On average, 47% of patients with COVID-19 self-report an olfactory disorder, although the inaccuracy of self-reporting means this figure may be higher.
On average, 47% of patients with COVID-19 self-report an olfactory disorder, although the inaccuracy of self-reporting means this figure may be higher.
Topics: Anosmia; COVID-19; Humans; Olfaction Disorders; SARS-CoV-2
PubMed: 35393605
DOI: 10.31128/AJGP-COVID-51-3 -
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 -
European Archives of... Feb 2023Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the causative agent of COVID-19 which was detected in late 2019 in Wuhan, China. As of September... (Review)
Review
Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is the causative agent of COVID-19 which was detected in late 2019 in Wuhan, China. As of September 2022, there have been over 612 million confirmed cases of COVID-19 with over 6.5 million associated deaths. In many cases, anosmia and dysgeusia have been identified as primary symptoms of COVID-19 infection in patients. While the loss of smell (anosmia) and loss of taste (dysgeusia) due to COVID-19 infection is transient in most patients, many report that these symptoms persist following recovery. Understanding the pathogenesis of these symptoms is paramount to early treatment of the infection. We conducted a literature review of Google Scholar and PubMed to find and analyze studies discussing anosmia and dysgeusia in the context of COVID-19 to understand the progression and management of these symptoms. The mechanism for dysgeusia is largely unknown; however, pathogenesis of anosmia includes inflammation and cytokine release resulting from the infection that alters neuronal signaling, thus inducing the loss of smell that patients experience. Anosmia may be managed and potentially resolved sooner with a combination therapy of olfactory training and budesonide irrigation of the nasal cavity. It is important to note that the variants of SARS-CoV-2 are genetically distinguished from the original virion due to a mutation in their spike proteins, giving them a different symptom profile regarding anosmia and dysgeusia. This variability in symptomatology is an area of study that needs to be further explored.
Topics: Humans; COVID-19; Dysgeusia; Anosmia; SARS-CoV-2; Pandemics; Olfaction Disorders
PubMed: 36209486
DOI: 10.1007/s00405-022-07689-w