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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 -
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 -
The Journal of Laryngology and Otology Sep 2023Smell impairment affects 60-80 per cent of individuals aged over 80 years. This review aimed to identify any association between vitamin D deficiency and smell... (Review)
Review
OBJECTIVE
Smell impairment affects 60-80 per cent of individuals aged over 80 years. This review aimed to identify any association between vitamin D deficiency and smell impairment, and determine the efficacy of vitamin D to treat smell impairment.
METHODS
A literature search was conducted across four databases between the years 2000 and 2022. The literature screen was performed by two independent reviewers.
RESULTS
Seven articles were included in this review. Four studies examined the association between vitamin D deficiency and smell impairment, with three studies identifying a significant relationship. Three studies investigated the use of vitamin D as treatment for smell impairment, which found complete resolution or significant symptom improvement after vitamin D deficiency was treated.
CONCLUSION
This review identified limited studies on this topic. As vitamin D supplementation is relatively cost-efficient, further large-scale studies should be carried out to investigate the efficacy of vitamin D for treating anosmia.
Topics: Humans; Aged, 80 and over; Vitamin D; Smell; Vitamins; Vitamin D Deficiency; Olfaction Disorders
PubMed: 36341550
DOI: 10.1017/S0022215122002389 -
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 -
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 -
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 -
Ear, Nose, & Throat Journal Jun 2024To systematically review the cases of anosmia or ageusia after receiving the coronavirus disease 2019 (COVID-19) vaccine. A systematic search was conducted in... (Review)
Review
To systematically review the cases of anosmia or ageusia after receiving the coronavirus disease 2019 (COVID-19) vaccine. A systematic search was conducted in electronic databases, including Web of Science, Scopus, Embase, and PubMed, to identify any published study that evaluated the anosmia or ageusia after receiving the COVID-19 vaccine, including case reports, case series, letter to editor articles with reported cases regarding our topic, or observational studies with at least 1 eligible patient consisted with our criteria. We excluded the studies that reported anosmia or ageusia due to COVID-19 infection and non-COVID-19 vaccines. Five studies consisting of 11 patients were included in this systematic review. Of the 11 patients, 5 patients had received the Pfizer COVID-19 vaccine and 6 patients received the Oxford-AstraZeneca COVID-19 vaccine, of which 6 patients developed symptoms after the first dose of vaccination and 5 patients were symptomatic after the second vaccine dose. Most of the patients developed symptoms within 1 week after the vaccination. The disorders of the patients included partial or total anosmia, parosmia, phantosmia, hyposmia, ageusia, and dysgeusia. Also, the patients had symptoms other than smell or taste disorders, including arthralgia, fever, chills, rhinorrhea, myalgia, abdominal pain, fatigue, muscle weakness, altered bowel pattern, aural fullness, tinnitus, and headache. Most of the evaluated patients did not receive any treatment as for their disorders. However, in some cases, treatment with oral corticosteroids or dietary supplementation was required. Anosmia and ageusia are important symptoms of COVID-19 vaccination. These symptoms will resolve without any treatment in most cases, although some interventions may be needed in some patients.
Topics: Humans; Ageusia; Anosmia; COVID-19; COVID-19 Vaccines; Female; Male; Vaccination; SARS-CoV-2; Middle Aged; Adult; BNT162 Vaccine; Aged
PubMed: 38411125
DOI: 10.1177/01455613241233098 -
The International Journal of... Jul 2023The current pandemic caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is accompanied with a rapid increase of reports and papers detailing its... (Meta-Analysis)
Meta-Analysis
The current pandemic caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is accompanied with a rapid increase of reports and papers detailing its neurological effects and symptoms. The virus infection causes respiratory illness named by the world health organization as corona virus 19 (COVID-19).This systematic review aims to study and summarize the different neurological manifestations of this virus. All articles published and indexed via Pubmed, Medline and Google Scholar databases between January 1st 2020 and February 28th 2021 that reported neurological symptoms of SARS-CoV-2 are reviewed following the Preferred Reporting Items for Systemic review and Meta-Analysis (PRISMA) guidelines.We included data from 113 articles: eight prospective studies, 25 retrospective studies and the rest were case reports/series. COVID-19 can present with central nervous system manifestations, such as headache, encephalitis and encephalopathy, peripheral nervous system manifestations, such as anosmia, ageusia and Guillian Barre syndrome, and skeletal muscle manifestations, such as myalgia and myasthenia gravis. Our systematic review showed that COVID-19 can be manifested by a wide spectrum of neurological symptoms reported either in the early stage or within the course of the disease. However, a detailed comprehension of these manifestations is required and more studies are needed in order to improve our scientific knowledge and to develop preventive and therapeutic measures to control this pandemic.
Topics: Humans; COVID-19; SARS-CoV-2; Nervous System Diseases; Comprehension; Prospective Studies; Retrospective Studies
PubMed: 34433369
DOI: 10.1080/00207454.2021.1973000 -
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 -
Current Treatment Options in Neurology 2020To investigate the association between the olfactory dysfunction and the more typical symptoms (fever, cough, dyspnoea) within the Sars-CoV-2 infection (COVID-19) in... (Review)
Review
PURPOSE OF REVIEW
To investigate the association between the olfactory dysfunction and the more typical symptoms (fever, cough, dyspnoea) within the Sars-CoV-2 infection (COVID-19) in hospitalized and non-hospitalized patients.
RECENT FINDINGS
PubMed, Scopus and Web of Science databases were reviewed from May 5, 2020, to June 1, 2020. Inclusion criteria included English, French, German, Spanish or Italian language studies containing original data related to COVID19, anosmia, fever, cough, and dyspnoea, in both hospital and non-hospital settings. Two investigators independently reviewed all manuscripts and performed quality assessment and quantitative meta-analysis using validated tools. A third author arbitrated full-text disagreements. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), 11 of 135 studies fulfilled eligibility. Anosmia was estimated less prevalent than fever and cough (respectively rate difference = - 0.316, 95% CI: - 0.574 to - 0.058, = - 2.404, < 0.016, = 11 and rate difference = - 0.249, 95% CI: - 0.402 to - 0.096, = - 3.185, < 0.001, = 11); the analysis between anosmia and dyspnoea was not significant (rate difference = - 0.008, 95% CI: - 0.166 to 0.150, Z = - 0.099, < 0.921, = 8). The typical symptoms were significantly more frequent than anosmia in hospitalized more critical patients than in non-hospitalized ones (respectively [(1) = 50.638 < 0.000, (1) = 52.520 < 0.000, (1) = 100.734 < 0.000).
SUMMARY
Patient with new onset olfactory dysfunction should be investigated for COVID-19. Anosmia is more frequent in non-hospitalized COVID-19 patients than in hospitalized ones.
PubMed: 32874091
DOI: 10.1007/s11940-020-00641-5