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Clinical Neurology and Neurosurgery Aug 2021We reviewed the literature on cerebrospinal fluid (CSF) testing in patients with altered olfactory/gustatory function due to COVID-19 for evidence of viral neuroinvasion.
OBJECTIVE
We reviewed the literature on cerebrospinal fluid (CSF) testing in patients with altered olfactory/gustatory function due to COVID-19 for evidence of viral neuroinvasion.
METHODS
We performed a systematic review of Medline and Embase to identify publications that described at least one patient with COVID-19 who had altered olfactory/gustatory function and had CSF testing performed. The search ranged from December 1, 2019 to November 18, 2020.
RESULTS
We identified 51 publications that described 70 patients who met inclusion criteria. Of 51 patients who had CSF SARS-CoV-2 PCR testing, 3 (6%) patients had positive results and 1 (2%) patient had indeterminate results. Cycle threshold (Ct; the number of amplification cycles required for the target gene to exceed the threshold, which is inversely related to viral load) was not provided for the patients with a positive PCR. The patient with indeterminate results had a Ct of 37 initially, then no evidence of SARS-CoV-2 RNA on repeat testing. Of 6 patients who had CSF SARS-CoV-2 antibody testing, 3 (50%) were positive. Testing to distinguish intrathecal antibody synthesis from transudation of antibodies to the CSF via breakdown of the blood-brain barrier was performed in 1/3 (33%) patients; this demonstrated antibody transmission to the CSF via transudation.
CONCLUSION
Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare in patients with altered olfactory/gustatory function. While pathology studies are needed, our review suggests it is unlikely that these symptoms are related to viral neuroinvasion.
Topics: Biomarkers; COVID-19; Humans; Olfaction Disorders; Taste Disorders
PubMed: 34146842
DOI: 10.1016/j.clineuro.2021.106760 -
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 -
The Cochrane Database of Systematic... Feb 2021The clinical implications of SARS-CoV-2 infection are highly variable. Some people with SARS-CoV-2 infection remain asymptomatic, whilst the infection can cause mild to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical implications of SARS-CoV-2 infection are highly variable. Some people with SARS-CoV-2 infection remain asymptomatic, whilst the infection can cause mild to moderate COVID-19 and COVID-19 pneumonia in others. This can lead to some people requiring intensive care support and, in some cases, to death, especially in older adults. Symptoms such as fever, cough, or loss of smell or taste, and signs such as oxygen saturation are the first and most readily available diagnostic information. Such information could be used to either rule out COVID-19, or select patients for further testing. This is an update of this review, the first version of which published in July 2020.
OBJECTIVES
To assess the diagnostic accuracy of signs and symptoms to determine if a person presenting in primary care or to hospital outpatient settings, such as the emergency department or dedicated COVID-19 clinics, has COVID-19.
SEARCH METHODS
For this review iteration we undertook electronic searches up to 15 July 2020 in the Cochrane COVID-19 Study Register and the University of Bern living search database. In addition, we checked repositories of COVID-19 publications. We did not apply any language restrictions.
SELECTION CRITERIA
Studies were eligible if they included patients with clinically suspected COVID-19, or if they recruited known cases with COVID-19 and controls without COVID-19. Studies were eligible when they recruited patients presenting to primary care or hospital outpatient settings. Studies in hospitalised patients were only included if symptoms and signs were recorded on admission or at presentation. Studies including patients who contracted SARS-CoV-2 infection while admitted to hospital were not eligible. The minimum eligible sample size of studies was 10 participants. All signs and symptoms were eligible for this review, including individual signs and symptoms or combinations. We accepted a range of reference standards.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently selected all studies, at both title and abstract stage and full-text stage. They resolved any disagreements by discussion with a third review author. Two review authors independently extracted data and resolved disagreements by discussion with a third review author. Two review authors independently assessed risk of bias using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. We presented sensitivity and specificity in paired forest plots, in receiver operating characteristic space and in dumbbell plots. We estimated summary parameters using a bivariate random-effects meta-analysis whenever five or more primary studies were available, and whenever heterogeneity across studies was deemed acceptable.
MAIN RESULTS
We identified 44 studies including 26,884 participants in total. Prevalence of COVID-19 varied from 3% to 71% with a median of 21%. There were three studies from primary care settings (1824 participants), nine studies from outpatient testing centres (10,717 participants), 12 studies performed in hospital outpatient wards (5061 participants), seven studies in hospitalised patients (1048 participants), 10 studies in the emergency department (3173 participants), and three studies in which the setting was not specified (5061 participants). The studies did not clearly distinguish mild from severe COVID-19, so we present the results for all disease severities together. Fifteen studies had a high risk of bias for selection of participants because inclusion in the studies depended on the applicable testing and referral protocols, which included many of the signs and symptoms under study in this review. This may have especially influenced the sensitivity of those features used in referral protocols, such as fever and cough. Five studies only included participants with pneumonia on imaging, suggesting that this is a highly selected population. In an additional 12 studies, we were unable to assess the risk for selection bias. This makes it very difficult to judge the validity of the diagnostic accuracy of the signs and symptoms from these included studies. The applicability of the results of this review update improved in comparison with the original review. A greater proportion of studies included participants who presented to outpatient settings, which is where the majority of clinical assessments for COVID-19 take place. However, still none of the studies presented any data on children separately, and only one focused specifically on older adults. We found data on 84 signs and symptoms. Results were highly variable across studies. Most had very low sensitivity and high specificity. Only cough (25 studies) and fever (7 studies) had a pooled sensitivity of at least 50% but specificities were moderate to low. Cough had a sensitivity of 67.4% (95% confidence interval (CI) 59.8% to 74.1%) and specificity of 35.0% (95% CI 28.7% to 41.9%). Fever had a sensitivity of 53.8% (95% CI 35.0% to 71.7%) and a specificity of 67.4% (95% CI 53.3% to 78.9%). The pooled positive likelihood ratio of cough was only 1.04 (95% CI 0.97 to 1.11) and that of fever 1.65 (95% CI 1.41 to 1.93). Anosmia alone (11 studies), ageusia alone (6 studies), and anosmia or ageusia (6 studies) had sensitivities below 50% but specificities over 90%. Anosmia had a pooled sensitivity of 28.0% (95% CI 17.7% to 41.3%) and a specificity of 93.4% (95% CI 88.3% to 96.4%). Ageusia had a pooled sensitivity of 24.8% (95% CI 12.4% to 43.5%) and a specificity of 91.4% (95% CI 81.3% to 96.3%). Anosmia or ageusia had a pooled sensitivity of 41.0% (95% CI 27.0% to 56.6%) and a specificity of 90.5% (95% CI 81.2% to 95.4%). The pooled positive likelihood ratios of anosmia alone and anosmia or ageusia were 4.25 (95% CI 3.17 to 5.71) and 4.31 (95% CI 3.00 to 6.18) respectively, which is just below our arbitrary definition of a 'red flag', that is, a positive likelihood ratio of at least 5. The pooled positive likelihood ratio of ageusia alone was only 2.88 (95% CI 2.02 to 4.09). Only two studies assessed combinations of different signs and symptoms, mostly combining fever and cough with other symptoms. These combinations had a specificity above 80%, but at the cost of very low sensitivity (< 30%).
AUTHORS' CONCLUSIONS
The majority of individual signs and symptoms included in this review appear to have very poor diagnostic accuracy, although this should be interpreted in the context of selection bias and heterogeneity between studies. Based on currently available data, neither absence nor presence of signs or symptoms are accurate enough to rule in or rule out COVID-19. The presence of anosmia or ageusia may be useful as a red flag for COVID-19. The presence of fever or cough, given their high sensitivities, may also be useful to identify people for further testing. Prospective studies in an unselected population presenting to primary care or hospital outpatient settings, examining combinations of signs and symptoms to evaluate the syndromic presentation of COVID-19, are still urgently needed. Results from such studies could inform subsequent management decisions.
Topics: Ageusia; Ambulatory Care; Anosmia; Arthralgia; Bias; COVID-19; Cough; Diarrhea; Dyspnea; Fatigue; Fever; Headache; Humans; Myalgia; Outpatient Clinics, Hospital; Pandemics; Physical Examination; Primary Health Care; SARS-CoV-2; Selection Bias; Symptom Assessment
PubMed: 33620086
DOI: 10.1002/14651858.CD013665.pub2 -
Reviews in the Neurosciences Apr 2021The ongoing pandemic of Coronavirus disease 2019 (COVID-19) has infected more than 27 million confirmed cases and 8,90,000 deaths all around the world. Verity of viral... (Meta-Analysis)
Meta-Analysis
The ongoing pandemic of Coronavirus disease 2019 (COVID-19) has infected more than 27 million confirmed cases and 8,90,000 deaths all around the world. Verity of viral infections can infect the nervous system; these viral infections can present a wide range of manifestation. The aim of the current study was to systematically review the COVID-19 associated central nervous system manifestations, mental and neurological symptoms. For that we conducted a comprehensive systematic literature review of four online databases, including Web of Science, PubMed, Scopus and Embase. All relevant articles that reported psychiatric/psychological symptoms or disorders in COVID-19 without considering time and language restrictions were assessed. All the study procedures were performed based on the PRISMA criteria. Due to the screening, 14 studies were included. The current study result indicated that, the pooled prevalence of CNS or mental associated disorders with 95% CI was 50.68% (6.68-93.88). The most prevalence symptoms were hyposmia/anosmia/olfactory dysfunction (number of study: 10) with 36.20% (14.99-60.51). Only one study reported numbness/paresthesia and dysphonia. Pooled prevalence of numbness/paresthesia and dysphonia was 5.83% (2.17-12.25) and 2.39% (10.75-14.22). The pooled prevalence of depression and anxiety was 3.52% (2.62-4.54) and 13.92% (9.44-19.08). Our findings demonstrate that COVID-19 has a certain relation with neurological symptoms. The hypsomia, anosmia or olfactory dysfunction was most frequent symptom. Other symptoms were headache or dizziness, dysgeusia or ageusia, dysphonia and fatigue. Depression, anxiety, and confusion were less frequent symptoms.
Topics: Anosmia; Anxiety; COVID-19; Depression; Dysgeusia; Dysphonia; Fatigue; Headache; Humans; Hypesthesia; Nervous System Diseases; Paresthesia; Prevalence; SARS-CoV-2
PubMed: 33618441
DOI: 10.1515/revneuro-2020-0108 -
The Egyptian Journal of Neurology,... 2021COVID-19 infection can show various manifestation, including neurologic manifestations, such as , , or , and causes the neurologic disorder such as stroke,... (Review)
Review
BACKGROUND
COVID-19 infection can show various manifestation, including neurologic manifestations, such as , , or , and causes the neurologic disorder such as stroke, Guillain-Barre syndrome, encephalopathy, and many more.
AIM
To briefly review neurologic manifestation in COVID-19 infection in the Asia region (South East Asia and the Western Pacific Region).
MATERIAL AND METHODS
This review uses the PRISMA statement and checklist. The source for reviewed article was performed in PubMed that were published between December 2019 to September 2020 with the latest 1 year of publication. Study titles were first screened, then reviewed by title and abstract and then the last review, we tested full text and applied eligibility criteria.
RESULTS
We found a total of 9 retrieved articles from the electronic database. Among these 9 articles, 5 of them are case report, 1 case series, 1 prospective multi-center cohort study, 1 retrospective multi-center study, and 1 retrospective observational study. All articles reported confirmed COVID-19, confirmation by positive swab test using the real-time RT-PCR method, with neurologic manifestations, disorder, or syndrome on presentation or found during hospital stay. In case of neurologic disorder or syndrome, the studies reported encephalitis and ADEM, acute cerebrovascular disease, acute symptomatic seizure, and Guillain-Barré syndrome with acute cerebrovascular disease as the most common neurologic disorder associated with COVID-19 infection, followed by encephalitis.
CONCLUSION
COVID-19 also affects the brain, which may result in a global or focal neurologic manifestation. Healthcare provider treating patient with COVID-19 infection should also be aware of neurologic manifestation associated with COVID-19 infection to improve patient's outcome.Guillain-Barre syndrome, encephalopathy, and many more. This review will briefly review neurologic manifestation in COVID-19 infection in the Asian region (South East Asia and the Western Pacific Region. A total of 9 retrieved articles from the electronic database reported confirmed COVID-19, confirmation by RT-PCR method, with neurologic manifestation, disorder, or syndrome on presentation or found during hospital stay. Healthcare provider treating patient with COVID-19 infection should also be aware of neurologic manifestation associated with COVID-19 infection to improve patient's outcome.
PubMed: 33613024
DOI: 10.1186/s41983-021-00279-3 -
Clinical and Experimental... Aug 2021This study evaluated the diagnostic value of various symptoms of coronavirus disease 2019 (COVID-19) in screening for this disease.
OBJECTIVES
This study evaluated the diagnostic value of various symptoms of coronavirus disease 2019 (COVID-19) in screening for this disease.
METHODS
Two authors (working independently) comprehensively reviewed six databases (PubMed, Cochrane Database, Embase, Web of Science, Scopus, and Google Scholar) from their dates of inception until November 2020. The predictive value of patient-reported symptoms, including otolaryngologic and general symptoms, was evaluated in adults who underwent testing for COVID-19. True-positive, true-negative, false-positive, and false-negative data were extracted from each study. The methodological quality of the included studies was evaluated using the quality assessment of diagnostic accuracy studies tool (ver. 2).
RESULTS
Twenty-eight prospective and retrospective studies were included in the meta-analysis. The diagnostic odds ratio (DOR) of a change in olfaction and/or taste was 10.20 (95% confidence interval [CI], 8.43-12.34). The area under the summary receiver operating characteristic curve was 0.8. Olfactory and/or taste changes had a low sensitivity (0.57; 95% CI, 0.47-0.66) but moderate negative (0.78; 95% CI, 0.69-0.85] and positive (0.78; 95% CI, 0.66-0.87) predictive values and a high specificity (0.91; 95% CI, 0.83-0.96). Olfactory and/or taste changes had a higher diagnostic value than the other otolaryngologic symptoms, a higher DOR and specificity, and a similar or higher diagnostic value than the other general symptoms.
CONCLUSION
Among otolaryngologic symptoms, olfactory and/or taste dysfunction was the most closely associated with COVID-19 and its general symptoms, and should therefore be considered when screening for the disease.
PubMed: 33541033
DOI: 10.21053/ceo.2020.02369 -
Journal of Medical Virology May 2021A meta-analysis was performed to identify patients with coronavirus disease 2019 (COVID-19) presenting with gastrointestinal (GI) symptoms during the first and second... (Meta-Analysis)
Meta-Analysis
A meta-analysis was performed to identify patients with coronavirus disease 2019 (COVID-19) presenting with gastrointestinal (GI) symptoms during the first and second pandemic waves and investigate their association with the disease outcomes. A systematic search in PubMed, Scopus, Web of Science, ScienceDirect, and EMBASE was performed up to July 25, 2020. The pooled prevalence of the GI presentations was estimated using the random-effects model. Pairwise comparison for the outcomes was performed according to the GI manifestations' presentation and the pandemic wave of infection. Data were reported as relative risk (RR), or odds ratio and 95% confidence interval. Of 125 articles with 25,252 patients, 20.3% presented with GI manifestations. Anorexia (19.9%), dysgeusia/ageusia (15.4%), diarrhea (13.2%), nausea (10.3%), and hematemesis (9.1%) were the most common. About 26.7% had confirmed positive fecal RNA, with persistent viral shedding for an average time of 19.2 days before being negative. Patients presenting with GI symptoms on admission showed a higher risk of complications, including acute respiratory distress syndrome (RR = 8.16), acute cardiac injury (RR = 5.36), and acute kidney injury (RR = 5.52), intensive care unit (ICU) admission (RR = 2.56), and mortality (RR = 2.01). Although not reach significant levels, subgroup-analysis revealed that affected cohorts in the first wave had a higher risk of being hospitalized, ventilated, ICU admitted, and expired. This meta-analysis suggests an association between GI symptoms in COVID-19 patients and unfavorable outcomes. The analysis also showed improved overall outcomes for COVID-19 patients during the second wave compared to the first wave of the outbreak.
Topics: Ageusia; Anorexia; COVID-19; Databases, Factual; Diarrhea; Dysgeusia; Feces; Gastroenterology; Hematemesis; Hospitalization; Humans; Nausea; Pandemics; Prevalence; SARS-CoV-2; Virus Shedding; COVID-19 Drug Treatment
PubMed: 33527440
DOI: 10.1002/jmv.26836 -
Brain, Behavior, & Immunity - Health May 2020Reports of neurological involvement during Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection course are increasingly described. The aim of this... (Review)
Review
OBJECTIVE
Reports of neurological involvement during Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection course are increasingly described. The aim of this review is to provide a clinical approach of SARS-CoV-2 neurological complications based on the direct or indirect (systemic/immune-mediated) role of the SARS-CoV-2 in their genesis.
METHODS
A review of the current literature has been carried out up to May 20th 2020 according to the PRISMA guidelines. All case series and reports of adult neurological manifestations associated to SARS-CoV-2 published in English were considered. Review and fundamental research studies on Coronaviruses neuroinvasive potential were analyzed to support pathogenic hypothesis and possible underlying mechanisms. Clinical patterns were subdivided into three groups according to putative underlying mechanisms: direct invasion of central or peripheral nervous system, systemic disorders leading to acute CNS injuries and post-infectious neurological syndromes (PINS).
RESULTS
Sixteen case series and 26 case reports for a total of 903 patients were identified presenting with neurological involvement during SARS-CoV-2 infection. Hypo/anosmia and dys/ageusia were found in 826 patients and mainly attributed to direct viral invasion. Cerebrovascular complications occurred in 51 patients and related to viral infection associated systemic inflammation. PINS were described in only 26 patients. A wide heterogeneity of these reports emerged concerning the extension of the clinical examination and ancillary exams performed.
CONCLUSIONS
Neurological complications of SARS-CoV-2 are mainly related to olfactory and gustatory sensory perception disorders through possible direct nervous system invasion while cerebrovascular disease and PINS are rare and due to distinct and indirect pathophysiological mechanisms.
PubMed: 33521692
DOI: 10.1016/j.bbih.2020.100094 -
American Journal of Otolaryngology 2021The aim of the study was to conduct a systematic review of the literature to investigate the time of onset and duration of symptoms of loss of smell and taste in...
OBJECTIVE
The aim of the study was to conduct a systematic review of the literature to investigate the time of onset and duration of symptoms of loss of smell and taste in patients diagnosed with COVID-19.
METHODS
Two independent authors performed a systematic review of the Medline/PubMed, SCOPUS, COCHRANE, Lilacs and Web of Science electronic databases. The time of onset and duration of symptoms were considered primary outcomes. The sex and age of individuals, the geographical location of the study, the prevalence of symptoms, other associated symptoms, associated comorbidities, and the impact on quality of life and eating habits were considered secondary outcomes.
RESULTS
Our search generated 17 articles. Many of the studies reported that the onset of anosmia and ageusia occurred 4 to 5 days after the manifestation of other symptoms of the infection and that these symptoms started to disappear after one week, with more significant improvements in the first two weeks.
CONCLUSION
The present study concludes that the onset of symptoms of loss of smell and taste, associated with COVID-19, occurs 4 to 5 days after other symptoms, and that these symptoms last from 7 to 14 days. Findings, however, varied and there is therefore a need for further studies to clarify the occurrence of these symptoms. This would help to provide early diagnosis and reduce contagion by the virus.
Topics: Ageusia; Anosmia; COVID-19; Humans; Time Factors
PubMed: 33445036
DOI: 10.1016/j.amjoto.2020.102889 -
Journal of Global Health Dec 2020It is of paramount importance to understand the transmission of SARS-CoV-2 in schools, which could support the decision-making about educational facilities closure or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
It is of paramount importance to understand the transmission of SARS-CoV-2 in schools, which could support the decision-making about educational facilities closure or re-opening with effective prevention and control measures in place.
METHODS
We conducted a systematic review and meta-analysis to investigate the extent of SARS-CoV-2 transmission in schools. We performed risk of bias evaluation of all included studies using the Newcastle-Ottawa Scale (NOS).
RESULTS
2178 articles were retrieved and 11 studies were included. Five cohort studies reported a combined 22 student and 21 staff index cases that exposed 3345 contacts with 18 transmissions (overall infection attack rate (IAR): 0.08%, 95% confidence interval (CI) = 0.00%-0.86%). IARs for students and school staff were 0.15% (95% CI = 0.00%-0.93%) and 0.70% (95% CI = 0.00%-3.56%) respectively. Six cross-sectional studies reported 639 SARS-CoV-2 positive cases in 6682 study participants tested [overall SARS-CoV-2 positivity rate: 8.00% (95% CI = 2.17%-16.95%). SARS-CoV-2 positivity rate was estimated to be 8.74% (95% CI = 2.34%-18.53%) among students, compared to 13.68% (95% CI = 1.68%-33.89%) among school staff. Gender differences were not found for secondary infection (OR = 1.44, 95% CI = 0.50-4.14, = 0.49) and SARS-CoV-2 positivity (OR = 0.90, 95% CI = 0.72-1.13, = 0.36) in schools. Fever, cough, dyspnea, ageusia, anosmia, rhinitis, sore throat, headache, myalgia, asthenia, and diarrhoea were all associated with the detection of SARS-CoV-2 antibodies (based on two studies). Overall, study quality was judged to be poor with risk of performance and attrition bias, limiting the confidence in the results.
CONCLUSIONS
There is limited high-quality evidence available to quantify the extent of SARS-CoV-2 transmission in schools or to compare it to community transmission. Emerging evidence suggests lower IAR and SARS-CoV-2 positivity rate in students compared to school staff. Future prospective and adequately controlled cohort studies are necessary to confirm this finding.
Topics: Adolescent; COVID-19; Child; Cross-Sectional Studies; Disease Transmission, Infectious; Female; Humans; Male; SARS-CoV-2; Schools; Students
PubMed: 33437465
DOI: 10.7189/jogh.10.021104