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International Journal of Preventive... 2021Evidence showed that partial or complete loss of smell and taste might be a possible primary symptom of the 2019 novel coronavirus (COVID-19). This study aimed to... (Review)
Review
BACKGROUND
Evidence showed that partial or complete loss of smell and taste might be a possible primary symptom of the 2019 novel coronavirus (COVID-19). This study aimed to systematically review and pool all available evidence on the olfactory and gustatory dysfunction in COVID-19 patients.
METHODS
In this systematic review, a comprehensive search was carried out systematically through e-databases including PubMed, EMBASE, Scopus, and Web of Science (WoS); that was limited to English-language studies published from 2019 up to 6 May 2020. Afterward, all studies reported the taste and smell dysfunction in the COVID-19 patients were included. The quality of the studies was assessed by the Mixed Methods Appraisal Tool (MMAT). The pooled prevalence of olfactory and gustatory dysfunction was estimated using the random effects meta-analysis method.
RESULTS
Among 28 eligible included studies in this systematic review, finally, 22 studies met the eligibility criteria and were included in the meta-analysis. According to the random effect meta-analysis, the global pooled prevalence (95% confidence interval) of any olfactory dysfunction, anosmia, and hyposmia was 55% (40%-70%), 40% (22%-57%), and 40% (20%-61%) respectively. The pooled estimated prevalence of any gustatory dysfunction, ageusia, and dysgeusia was 41% (23%-59%), 31% (3%-59%), and 34% (19%-48%) respectively.
CONCLUSIONS
Olfactory and gustatory dysfunction is prevalent among COVID-19 patients. Therefore, olfactory and gustatory dysfunction seems to be part of important symptoms and notify for the diagnosis of COVID-19, especially in the early phase of the infection.
PubMed: 35070203
DOI: 10.4103/ijpvm.IJPVM_484_20 -
Brazilian Journal of Otorhinolaryngology 2022SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins... (Review)
Review
INTRODUCTION
SARS-CoV-2 is the pathogen of COVID-19. The virus is composed of the spike, membrane and envelope. On physiological smell, odoriferous substances bind to proteins secreted by sustentacular cells in order to be processed by olfactory receptor neurons. Olfactory disorder is one of the main manifestations of COVID-19, however, research is still required to clarify the mechanism involved in SARS-CoV-2 induced anosmia.
OBJECTIVE
This article aims to analyze current scientific evidence intended to elucidate the pathophysiological relationship between COVID-19 and the cause of olfactory disorders.
METHODS
Pubmed, Embase, Scopus and ScienceDirect were used to compose this article. The research was conducted on November 24th, 2020. Original articles with experimental studies in human, animal and in vitro, short communications, viewpoint, published in the English language and between 2019 and 2020 were included, all related to the pathophysiological relationship between olfactory disorders and COVID-19 infection.
RESULTS
Both human cell receptors ACE2 and TMPRSS2 are essential for the SARS-CoV-2 entrance. These receptors are mostly present in the olfactory epithelium cells, therefore, the main hypothesis is that anosmia is caused due to damage to non-neuronal cells which, thereafter, affects the normal olfactory metabolism. Furthermore, magnetic resonance imaging studies exhibit a relationship between a reduction on the neuronal epithelium and the olfactory bulb atrophy. Damage to non-neuronal cells explains the average recovery lasting a few weeks. This injury can be exacerbated by an aggressive immune response, which leads to damage to neuronal cells and stem cells inducing a persistent anosmia. Conductive anosmia is not sufficient to explain most cases of COVID-19 induced anosmia.
CONCLUSION
Olfactory disorders such as anosmia and hyposmia can be caused by COVID-19, the main mechanism is associated with olfactory epithelium damage, targeting predominantly non-neuronal cells. However, neuronal cells can also be affected, worsening the condition of olfactory loss.
Topics: Angiotensin-Converting Enzyme 2; Animals; Anosmia; COVID-19; Humans; Olfaction Disorders; SARS-CoV-2; Smell
PubMed: 33965353
DOI: 10.1016/j.bjorl.2021.04.001 -
Chemical Senses Jul 2016Previous studies on the relationship between olfaction and depression have revealed mixed results. In addition, few have focused on the reciprocity of this association.... (Review)
Review
Previous studies on the relationship between olfaction and depression have revealed mixed results. In addition, few have focused on the reciprocity of this association. The aim of this study is to combine depression and olfactory data in two separate patient populations to further understand their association. A systematic literature review was conducted using 3 online databases to identify studies correlating olfaction and depression in patients presenting with either primary depression or primary olfactory dysfunction. For the depressed population, weighted means and standard deviations for the Sniffin' Sticks Test and the 40-item Smell Identification Test were combined using 10 studies. For the olfactory dysfunction population, weighted means of Beck's Depression Inventory were combined using 3 studies. Independent t-tests were used to compare differences between groups. Comparing primary depressed patients with controls, depressed patients showed decreased scores in olfactory threshold (6.31±1.38 vs. 6.78±0.88, P = 0.0005), discrimination (12.05±1.44 vs. 12.66±1.36, P = 0.0073), identification (12.57±0.74 vs. 12.98±0.90, P < 0.0001), and 40-Item Smell Identification Test (35.31±1.91 vs. 37.41±1.45, P < 0.0001). In patients with primary olfactory dysfunction, Beck's Depression Inventory scores were significantly different between patients classified as normosmics, hyposmics and anosmics (5.21±4.73 vs. 10.93±9.25 vs. 14.15±5.39, P ≤ 0.0274 for all 3 comparisons). In conclusion, patients with depression have reduced olfactory performance when compared with the healthy controls and conversely, patients with olfactory dysfunction, have symptoms of depression that worsen with severity of smell loss.
Topics: Depressive Disorder; Humans; Olfaction Disorders; Sensory Thresholds; Smell
PubMed: 27170667
DOI: 10.1093/chemse/bjw061 -
The Canadian Journal of Neurological... Jul 2022Coronavirus disease 2019 (COVID-19) has been associated with various neurological and atypical head/eyes/ears/nose/throat (HEENT) manifestations. We sought to review the... (Meta-Analysis)
Meta-Analysis
BACKGROUND/OBJECTIVE
Coronavirus disease 2019 (COVID-19) has been associated with various neurological and atypical head/eyes/ears/nose/throat (HEENT) manifestations. We sought to review the evidence for these manifestations.
METHODS
In this systematic review and meta-analysis, we compiled studies published until March 31, 2021 that examined non-respiratory HEENT, central, and peripheral nervous system presentations in COVID-19 patients. We included 477 studies for qualitative synthesis and 59 studies for meta-analyses.
RESULTS
Anosmia, ageusia, and conjunctivitis may precede typical upper/lower respiratory symptoms. Central nervous system (CNS) manifestations include stroke and encephalopathy, potentially with brainstem or cranial nerve involvement. MRI studies support CNS para-/postinfectious etiologies, but direct neuroinvasion seems very rare, with few cases detecting Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the CNS. Peripheral nervous system (PNS) manifestations include muscle damage, Guillain-Barre syndrome (GBS), and its variants. There was moderate-to-high study heterogeneity and risk of bias. In random-effects meta-analyses, anosmia/ageusia was estimated to occur in 56% of COVID-19 patients (95% CI: 0.41-0.71, I2:99.9%), more commonly than in patients without COVID-19 (OR: 14.28, 95% CI: 8.39-24.29, I2: 49.0%). Neurological symptoms were estimated to occur in 36% of hospitalized patients (95% CI: 0.31-0.42, I2: 99.8%); ischemic stroke in 3% (95% CI: 0.03-0.04, I2: 99.2%), and GBS in 0.04% (0.033%-0.047%), more commonly than in patients without COVID-19 (OR[stroke]: 2.53, 95% CI: 1.16-5.50, I2: 76.4%; OR[GBS]: 3.43,1.15-10.25, I2: 89.1%).
CONCLUSIONS
Current evidence is mostly from retrospective cohorts or series, largely in hospitalized or critically ill patients, not representative of typical community-dwelling patients. There remains a paucity of systematically gathered prospective data on neurological manifestations. Nevertheless, these findings support a high index of suspicion to identify HEENT/neurological presentations in patients with known COVID-19, and to test for COVID-19 in patients with such presentations at risk of infection.
Topics: Ageusia; Anosmia; COVID-19; Guillain-Barre Syndrome; Humans; Nervous System Diseases; Pharynx; Prospective Studies; Retrospective Studies; SARS-CoV-2; Stroke
PubMed: 34287109
DOI: 10.1017/cjn.2021.180 -
Brain, Behavior, & Immunity - Health Aug 2021Among Coronavirus Disease 2019 (COVID-19) manifestations, Olfactory (OD) and Gustatory (GD) Dysfunctions (OGD) have drawn considerable attention, becoming a sort of... (Review)
Review
BACKGROUND
Among Coronavirus Disease 2019 (COVID-19) manifestations, Olfactory (OD) and Gustatory (GD) Dysfunctions (OGD) have drawn considerable attention, becoming a sort of hallmark of the disease. Many have speculated on the pathogenesis and clinical characteristics of these disturbances; however, no definite answers have been produced on the topic. With this systematic review, we aimed to collect all the available evidence regarding the prevalence of OGD, the timing of their onset and their resolution, their rate of recovery and their role as diagnostic and prognostic tools for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection.
METHODS
A systematic review comprising all the observational studies that reported the prevalence and/or the longitudinal trajectories of OGD in COVID-19 patients, as self-reported by patients or measured through objective psychophysical tests.
RESULTS
After the selection process, 155 studies were included, with a total of 70,920 patients and 105,291 not-infected individuals. Prevalence reports were extremely variable across studies, with wide ranges for OD (0%-98%) and GD (0-89%) prevalence. OGD occurred early during the disease course and only rarely preceded other symptoms; out of 30 studies with a follow-up time of at least 20 days, only in 5 studies OGD fully resolved in more than 90% of patients. OGD had low sensitivity and high specificity for SARS-CoV-2 infection; accuracy of OD and GD for infection identification was higher than 80% in 10 out of 33 studies and in 8 out of 22 studies considered, respectively. 28 out of 30 studies that studied the association between OGD and disease severity found how OGD were associated with lower rates of severe pneumonia, hospitalization and mortality.
CONCLUSIONS
OGD seem to be highly prevalent in SARS-CoV-2 infection. They occur early, concomitantly with other symptoms and often persist after recovery, in some cases for months; whether a full recovery eventually occurs in all cases is not clear yet. OGD are good predictors of SARS-CoV-2 infection and are associated with a milder disease course.
PubMed: 34027497
DOI: 10.1016/j.bbih.2021.100268 -
Biomedicines Aug 2023Post-Covid Olfactory Dysfunction (PCOD) is characterized by olfactory abnormalities, hyposmia, and anosmia, which are among the most often enduring symptoms in... (Review)
Review
Post-Covid Olfactory Dysfunction (PCOD) is characterized by olfactory abnormalities, hyposmia, and anosmia, which are among the most often enduring symptoms in individuals who have recovered from SARS-CoV-2 infection. This disorder has been reported to persist in subsets of patients well after 12 months following infection, significantly affecting their quality of life. Despite the high prevalence of PCOD among patients who suffered from SARS-CoV-2 infection, specific therapeutic strategies are still limited. Among these, emerging evidence seems to indicate the administration of CoUltraPEALut, a combination of micronized Palmitoylethanolamide (PEA), an endogenous fatty acid amide, and Luteolin, a natural antioxidant flavonoid, as a viable therapy, especially when given as an adjuvant to olfactory training. Based on the above, a systematic review and a meta-analysis of the literature were conducted, with the aim of evaluating the efficacy of CoUltraPEALut as an addition to olfactory training (OT), in treating PCOD symptoms. Pubmed (MEDLINE), Embase (OVID), and Web of Science scientific databases were screened from the inception until 31 May 2023, and a total of 407 articles were recovered; only five of these studies (441 total patients between treated and control groups) were included in the systematic review. CoUltraPEALut demonstrated significant efficacy in the overall recovery of the olfactory function, compared to the conventional therapy, suggesting that it could represent a possible future adjuvant treatment for PCOD.
PubMed: 37626685
DOI: 10.3390/biomedicines11082189 -
Cureus Sep 2022Few studies have thoroughly evaluated the neuro-invasive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which may contribute to a... (Review)
Review
Few studies have thoroughly evaluated the neuro-invasive effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which may contribute to a wide range of sequelae from mild long-term effects like headaches and fatigue to severe events like stroke and arrhythmias. Our study aimed to evaluate the long-term neurological effects of coronavirus disease 2019 (COVID-19) among patients discharged from the hospital. In this systematic review and meta-analysis, we assessed the long-term neurocognitive effects of COVID-19. Post-COVID-19 neurological sequelae were defined as persistent symptoms of headache, fatigue, myalgia, anosmia, dysgeusia, sleep disturbance, issues with concentration, post-traumatic stress disorder (PTSD), suicidality, and depression long after the acute phase of COVID-19. Data from observational studies describing post-COVID-19 neurocognitive sequelae and severity of COVID-19 from September 1, 2019, to the present were extracted following the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol with a consensus of three independent reviewers. A systematic review was performed for qualitative evaluation and a meta-analysis was performed for quantitative analysis by calculating log odds of COVID-19 neurocognitive sequelae. The odds ratio (OR) and 95% confidence interval (CI) were obtained and forest plots were created using random effects models. We found seven studies, out of which three were used for quantitative synthesis of evidence. Of the 3,304 post-COVID-19 patients identified, 50.27% were male with a mean age of 56 years; 20.20% had post-COVID-19 symptoms more than two weeks after the acute phase of infection. Among persistence symptoms, neurocognitive symptoms like headache (27.8%), fatigue (26.7%), myalgia (23.14%), anosmia (22.8%), dysgeusia (12.1%), sleep disturbance (63.1%), confusion (32.6%), difficulty to concentrate (22%), and psychiatric symptoms like PTSD (31%), feeling depressed (20%), and suicidality (2%) had a higher prevalence. In meta-analysis, COVID-19 patients with severe symptoms had higher odds of headache (pooled OR: 4.53; 95% CI: 2.37-8.65; p<0.00001; I: 0%) and myalgia (pooled OR: 3.36; 95% CI: 2.71-4.17; p<0.00001; I: 0%). Anosmia, fatigue, and dysgeusia had higher but non-significant odds following COVID-19. Although we had sufficient data for headache and fatigue to identify higher rates and associations following COVID-19, we could not establish relationships with other post-COVID-19 neurocognitive séqueles. Long-term follow-up may mitigate the neurocognitive effects among COVID-19 patients as these symptoms are also associated with a poor quality of life.
PubMed: 36321004
DOI: 10.7759/cureus.29694 -
European Neurology 2021While the most common neurologic symptoms reported in patients affected by SARS-CoV-2 are headache, dizziness, myalgia, mental fog, and anosmia, there is a growing basis...
BACKGROUND
While the most common neurologic symptoms reported in patients affected by SARS-CoV-2 are headache, dizziness, myalgia, mental fog, and anosmia, there is a growing basis of published peer-reviewed cases reporting stroke in the setting of SARS-CoV-2 infection. The peer-reviewed literature suggests an increased risk of cerebrovascular accident (CVA) in the setting of COVID-19 infection.
METHODS
We searched 3 databases (PubMed, MEDLINE, and CINAHL) with search terms COVID-19, novel coronavirus, stroke, and cerebrovascular accident. Case series and case studies presenting patients positive for both COVID-19 and CVA published from January 1 through September 1, 2020, were included. Data collection and analysis was completed and risk of bias assessed.
RESULTS
The search identified 28 studies across 7 counties comprising 73 patients. Amongst patients hospitalized for COVID-19 infection and CVA, the average age was 60; the most common preexisting conditions were hypertension and diabetes mellitus, and those without preexisting conditions were significantly younger with an average age of 47. Amongst hospitalized patients with COVID-19 and CVA, there was a bimodal association with COVID-19 infection severity with majority of patients classified with mild or critical COVID-19 infection.
DISCUSSION
The data suggest SARS-CoV-2 is a risk factor for developing stroke, particularly in patients with hypertension and diabetes. Furthermore, the younger average age of stroke in patients with SARS-CoV-2, particularly those patients with zero identifiable preexisting conditions, creates high suspicion that SARS-CoV-2 is an independent risk factor for development of stroke; however, this cannot yet be proven without comparable control population. The data suggest the risk of developing CVA in the setting of COVID-19 infection is not dependent upon severity of illness. Continued studies must be done to understand the epidemiologic factors of COVID-19 infection and stroke and the pathophysiology of the COVID-associated hypercoagulable state.
Topics: COVID-19; Headache; Humans; Middle Aged; SARS-CoV-2; Stroke
PubMed: 34352787
DOI: 10.1159/000517403 -
Neuroscience and Biobehavioral Reviews Jun 2021Olfactory impairment is a common clinical motif across neurodevelopmental disorders, suggesting olfactory circuits are particularly vulnerable to disease processes and... (Review)
Review
Olfactory impairment is a common clinical motif across neurodevelopmental disorders, suggesting olfactory circuits are particularly vulnerable to disease processes and can provide insight into underlying disease mechanisms. The mouse olfactory bulb is an ideal model system to study mechanisms of neurodevelopmental disease due to its anatomical accessibility, behavioral relevance, ease of measuring circuit input and output, and the feature of adult neurogenesis. Despite the clinical relevance and experimental benefits, olfactory testing across animal models of neurodevelopmental disease has been inconsistent and non-standardized. Here we performed a systematic literature review of olfactory function testing in mouse models of neurodevelopmental disorders, and identified intriguing inconsistencies that include evidence for both increased and decreased acuity in odor detection in various mouse models of Autism Spectrum Disorder (ASD). Based on our identified gaps in the literature, we recommend direct comparison of different mouse models of ASD using standardized tests for odor detection and discrimination. This review provides a framework to guide future olfactory function testing in mouse models of neurodevelopmental diseases.
Topics: Adult; Animals; Autism Spectrum Disorder; Humans; Mice; Neurogenesis; Olfaction Disorders; Olfactory Bulb; Smell
PubMed: 33610612
DOI: 10.1016/j.neubiorev.2021.02.024 -
Frontiers in Neurology 2020Some of the symptoms of COVID-19 are fever, cough, and breathing difficulty. However, the mechanism of the disease, including some of the symptoms such as the...
Some of the symptoms of COVID-19 are fever, cough, and breathing difficulty. However, the mechanism of the disease, including some of the symptoms such as the neurological and musculoskeletal symptoms, is still poorly understood. The aim of this review is to summarize the evidence on the neurological and musculoskeletal symptoms of the disease. This may help with early diagnosis, prevention of disease spread, and treatment planning. MEDLINE, EMBASE, Web of Science, and Google Scholar (first 100 hits) were searched until April 17, 2020. The key search terms used were "coronavirus" and "signs and symptoms." Only studies written in English were included. The selection was performed by two independent reviewers using EndNote and Rayyan software. Any disagreement was resolved by consensus or by a third reviewer. PRISMA guidelines were followed for abstracting data and assessing the quality of the studies. These were carried out by two and three independent reviewers, respectively. Any disagreement was resolved by consensus or by a third reviewer. The data were analyzed using qualitative synthesis and pooled using a random-effect model. Main Outcome(s) and Measure(s): The outcomes in the study include country, study design, participant details (sex, age, sample size), and neurological and musculoskeletal features. Sixty studies ( = 11, 069) were included in the review, and 51 studies were used in the meta-analysis. The median or mean age ranged from 24 to 95 years. The prevalence of neurological and musculoskeletal manifestations was 35% for smell impairment (95% CI 0-94%; 99.63%), 33% for taste impairment (95% CI 0-91%; 99.58%), 19% for myalgia (95% CI 16-23; 95%), 12% for headache (95% CI 9-15; 93.12%), 10% for back pain (95% CI 1-23%; 80.20%), 10% for dizziness (95% CI 3-19%; 86.74%), 3% for acute cerebrovascular disease (95% CI 1-5%; 0%), and 2% for impaired consciousness (95% CI 1-2%; 0%). Patients with COVID-19 present with neurological and musculoskeletal symptoms. Therefore, clinicians need to be vigilant in the diagnosis and treatment of these patients.
PubMed: 32676052
DOI: 10.3389/fneur.2020.00687