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ACS Chemical Neuroscience Oct 2021The prevalence of chemosensory dysfunction in patients with COVID-19 varies greatly between populations. It is unclear whether such differences are due to factors at the... (Meta-Analysis)
Meta-Analysis
The prevalence of chemosensory dysfunction in patients with COVID-19 varies greatly between populations. It is unclear whether such differences are due to factors at the level of the human host, or at the level of the coronavirus, or both. At the host level, the entry proteins which allow virus binding and entry have variants with distinct properties, and the frequency of such variants differs between ethnicities. At the level of the virus, the D614G mutation enhances virus entry to the host cell. Since the two virus strains (D614 and G614) coexisted in the first six months of the pandemic in most populations, it has been difficult to distinguish between contributions of the virus and contributions of the host for anosmia. To answer this question, we conducted a systematic review and meta-analysis of studies in South Asian populations when either the D614 or the G614 virus was dominant. We show that populations infected predominantly with the G614 virus had a much higher prevalence of anosmia (pooled prevalence of 31.8%) compared with the same ethnic populations infected mostly with the D614 virus strain (pooled anosmia prevalence of 5.3%). We conclude that the D614G mutation is a major contributing factor that increases the prevalence of anosmia in COVID-19, and that this enhanced effect on olfaction constitutes a previously unrecognized phenotype of the D614G mutation. The new virus strains that have additional mutations on the background of the D614G mutation can be expected to cause a similarly increased prevalence of chemosensory dysfunctions.
Topics: Anosmia; COVID-19; Humans; Mutation; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 34533304
DOI: 10.1021/acschemneuro.1c00542 -
Journal of Medical Virology Jan 2022There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting... (Meta-Analysis)
Meta-Analysis
There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post-acute COVID-19 syndrome (PCS) and conducted meta-regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post-COVID-19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random-effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ-VAS) was (59%; 95% CI: 42%-75%). Based on individual factors in the EQ-5D-5L questionnaire, the prevalence of mobility was (36, 10-67), personal care (8, 1-21), usual quality (28, 2-65), pain/discomfort (42, 28-55), and anxiety/depression (38, 19-58). The prevalence of persistent symptoms was fatigue (64, 54-73), dyspnea (39.5, 20-60), anosmia (20, 15-24), arthralgia (24.3, 14-36), headache (21, 3-47), sleep disturbances (47, 7-89), and mental health (14.5, 4-29). Meta-regression analysis showed the poor quality of life was significantly higher among post-COVID-19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.
Topics: Adult; Age Factors; COVID-19; Female; Humans; Intensive Care Units; Male; Middle Aged; Quality of Life; Post-Acute COVID-19 Syndrome
PubMed: 34463956
DOI: 10.1002/jmv.27309 -
Neurology International Aug 2021SARS-CoV-2 infection in children produces mild respiratory symptoms or no symptoms at all in most cases. Some pediatric patients develop a severe complication associated... (Review)
Review
SARS-CoV-2 infection in children produces mild respiratory symptoms or no symptoms at all in most cases. Some pediatric patients develop a severe complication associated with high mortality, the multisystem inflammatory syndrome in children (MIS-C). In both scenarios, there are reports of neurological manifestations. This article aims to review the cases of pediatric patients with severe neurological issues and a coexisting positive SARS-CoV-2 test. A literature search was performed between March 2020 and May 2021. The results included the data from 41 studies, with 159 children with severe neurological manifestations, within an age range from 24 h to 17 years. The neurological disorders included 38 cases with stroke, 32 with encephalitis, 22 with encephalopathy, and 10 with Guillain-Barre syndrome. Sixty-five out of 159 cases with severe neurological manifestations were diagnosed with MIS-C. Direct neuroinvasion and the exaggerated immune response in some patients seem to be the most critical factors triggering these manifestations. Further research in the ongoing pandemic is needed to elucidate the precise mechanism.
PubMed: 34449704
DOI: 10.3390/neurolint13030041 -
International Journal of Environmental... Aug 2021Setting off a global pandemic, coronavirus disease 2019 (COVID-19) has been marked by a heterogeneous clinical presentation that runs the gamut from asymptomatic to... (Review)
Review
Setting off a global pandemic, coronavirus disease 2019 (COVID-19) has been marked by a heterogeneous clinical presentation that runs the gamut from asymptomatic to severe and fatal. Although less lethal in children than adults, COVID-19 has nonetheless afflicted the pediatric population. This systematic review used clinical information from published literature to assess the spectrum of COVID-19 presentation in children, with special emphasis on characteristics associated with multisystem inflammatory syndrome (MIS-C). An electronic literature search for English and Chinese language articles in COVIDSeer, MEDLINE, and PubMed from 1 January 2020 through 1 March 2021 returned 579 records, of which 54 were included for full evaluation. Out of the total 4811 patients, 543 (11.29%) exhibited MIS-C. The most common symptoms across all children were fever and sore throat. Children presenting with MIS-C were less likely to exhibit sore throat and respiratory symptoms (i.e., cough, shortness of breath) compared to children without MIS-C. Inflammatory (e.g., rash, fever, and weakness) and gastrointestinal (e.g., nausea/vomiting and diarrhea) symptoms were present to a greater extent in children with both COVID-19 and MIS-C, suggesting that children testing positive for COVID-19 and exhibiting such symptoms should be evaluated for MIS-C.
Topics: COVID-19; Child; Fever; Humans; Pandemics; SARS-CoV-2; Systemic Inflammatory Response Syndrome
PubMed: 34444014
DOI: 10.3390/ijerph18168269 -
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 -
Revista Da Associacao Medica Brasileira... Feb 2021Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can affect the nervous system, triggering problems such as the Guillain-Barre Syndrome (GBS), an...
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections can affect the nervous system, triggering problems such as the Guillain-Barre Syndrome (GBS), an association that can bring complications to the patient.
OBJECTIVE
This scoping review aimed to clarify the clinical features and analyze patients with GBS associated with SARS-CoV-2 infection, looking at morbidity, mortality, and neurological outcomes.
SEARCH STRATEGY
The search was conducted through Medline, Web of Science, Embase, CINAHAL, Latin-American and Caribbean Literature in Health Sciences (LILACS), clinicaltrials.gov, SCOPUS, and the Cochrane Central Register of Controlled Trials.
SELECTION CRITERIA
Observational studies, published after 2019, describe patients with GBS associated with SARS-CoV-2 infection. There were no language restrictions while selecting the studies.
DATA COLLECTION AND ANALYSIS
Three authors, Kleyton Santos de Medeiros, Luíza Thomé de Araújo Macêdo, and Wederson Farias de Souza, independently screened the search results using titles and abstracts. Duplicate studies were excluded. The same authors then went through the entire text to determine whether the studies met the inclusion criteria. Discrepancies were resolved by other reviewers, Ana Paula Ferreira Costa, Ayane Cristine Sarmento, and Ana Katherine Gonçalves. Finally, the selection of the studies was summarized in a PRISMA flow diagram.
MAIN RESULTS
Main manifestations were fever, coughing, dyspnea, sore throat, ageusia, anosmia, and respiratory failure, in addition to paresthesia of the upper and lower limbs, tetraparesis, facial diplegia, areflexia, asthenia, mastoid pain, acute ataxia, fatigue, numbness, swallowing disorder, and moderate low back pain.
CONCLUSION
Coronavirus disease 2019 (COVID-19) can trigger the GBS, despite the few studies on this topic. Patients had clinical manifestations of COVID-19 infection and neurological manifestations characterizing GBS.
Topics: COVID-19; Dyspnea; Fever; Guillain-Barre Syndrome; Humans; SARS-CoV-2
PubMed: 34406260
DOI: 10.1590/1806-9282.67.2.20200716 -
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 -
Archives of Pharmacal Research Jul 2021Anecdotal evidence suggests that the severity of coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is...
Anecdotal evidence suggests that the severity of coronavirus disease of 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is likely to be distinguished by variations in loss of smell (LOS). Thus, we conducted a meta-analysis of 45 articles that include a total of 42,120 COVID-19 patients from 17 different countries to demonstrate that severely ill or hospitalized COVID-19 patients have a lesser chance of experiencing LOS than non-severely ill or non-hospitalized COVID-19 patients (odds ratio = 0.527 [95% CI 0.373-0.744; p < 0.001] and 0.283 [95% CI 0.173-0.462; p < 0.001], respectively). We also proposed a possible mechanism underlying the association of COVID-19 severity with anosmia, which may explain why patients without sense of smell develop severe COVID-19. Variations in LOS according to the severity of COVID-19 is a global phenomenon, with few exceptions. Since severely ill patients have a lower rate of anosmia, patients without anosmia should be monitored more closely in the early stages of COVID-19, for early diagnosis of severity of illness. An understanding of how the severity of COVID-19 infection and LOS are associated has profound implications for the clinical management and mitigation strategies for the disease.
Topics: Anosmia; COVID-19; Early Diagnosis; Female; Hospitalization; Humans; Male; Odorants; Olfactory Perception; Predictive Value of Tests; Prognosis; Risk Assessment; Risk Factors; Severity of Illness Index; Smell
PubMed: 34302637
DOI: 10.1007/s12272-021-01344-4 -
The Cochrane Database of Systematic... Jul 2021Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can...
BACKGROUND
Olfactory dysfunction is an early and sensitive marker of COVID-19 infection. Although self-limiting in the majority of cases, when hyposmia or anosmia persists it can have a profound effect on quality of life. Little guidance exists on the treatment of post-COVID-19 olfactory dysfunction, however several strategies have been proposed from the evidence relating to the treatment of post-viral anosmia (such as medication or olfactory training).
OBJECTIVES
To assess the effects (benefits and harms) of interventions that have been used, or proposed, to treat persisting olfactory dysfunction due to COVID-19 infection. A secondary objective is to keep the evidence up-to-date, using a living systematic review approach. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane COVID-19 Study Register; Cochrane ENT Register; CENTRAL; Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished studies. The date of the search was 16 December 2020.
SELECTION CRITERIA
Randomised controlled trials including participants who had symptoms of olfactory disturbance following COVID-19 infection. Only individuals who had symptoms for at least four weeks were included in this review. Studies compared any intervention with no treatment or placebo.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. 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 one study with 18 participants, which compared the use of a 15-day course of oral steroids combined with nasal irrigation (consisting of an intranasal steroid/mucolytic/decongestant solution) with no intervention. Psychophysical testing was used to assess olfactory function at baseline, 20 and 40 days. Systemic corticosteroids plus intranasal steroid/mucolytic/decongestant compared to no intervention Recovery of sense of smell was assessed after 40 days (25 days after cessation of treatment) using the Connecticut Chemosensory Clinical Research Center (CCCRC) score. This tool has a range of 0 to 100, and a score of ≥ 90 represents normal olfactory function. The evidence is very uncertain about the effect of this intervention on recovery of the sense of smell at one to three months (5/9 participants in the intervention group scored ≥ 90 compared to 0/9 in the control group; risk ratio (RR) 11.00, 95% confidence interval (CI) 0.70 to 173.66; 1 study; 18 participants; very low-certainty evidence). Change in sense of smell was assessed using the CCCRC score at 40 days. This study reported an improvement in sense of smell in the intervention group from baseline (median improvement in CCCRC score 60, interquartile range (IQR) 40) compared to the control group (median improvement in CCCRC score 30, IQR 25) (1 study; 18 participants; very low-certainty evidence). Serious adverse events andother adverse events were not identified in any participants of this study; however, it is unclear how these outcomes were assessed and recorded (1 study; 18 participants; very low-certainty evidence).
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 other ongoing trials in this area. As this is a living systematic review we will update the data regularly, as new results become available. For this (first) version of the living review we identified only one study with a small sample size, which assessed systemic steroids and nasal irrigation (intranasal steroid/mucolytic/decongestant). However, the evidence regarding the benefits and harms from this intervention to treat persistent post-COVID-19 olfactory dysfunction is very uncertain.
Topics: Administration, Oral; Ambroxol; Betamethasone; Bias; COVID-19; Expectorants; Glucocorticoids; Humans; Nasal Decongestants; Nasal Lavage; Olfaction Disorders; Prednisone; Prevalence; Quality of Life; Recovery of Function; Smell; Time Factors
PubMed: 34291813
DOI: 10.1002/14651858.CD013876.pub2 -
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