Neurological manifestations and complications of coronavirus disease 2019 (COVID-19): a systematic review and meta-analysis

Abstract Background The spectrum of neurological involvement in COVID-19 is not thoroughly understood. To the best of our knowledge, no systematic review with meta-analysis and a sub-group comparison between severe and non-severe cases has been published. The aim of this study is to assess the frequency of neurological manifestations and complications, identify the neurodiagnostic findings, and compare these aspects between severe and non-severe COVID-19 cases. Methods A systematic search of PubMed, Scopus, EBSCO, Web of Science, and Google Scholar databases was conducted for studies published between the 1st of January 2020 and 22nd of April 2020. In addition, we scanned the bibliography of included studies to identify other potentially eligible studies. The criteria for eligibility included studies published in English language (or translated to English), those involving patients with COVID-19 of all age groups, and reporting neurological findings. Data were extracted from eligible studies. Meta-analyses were conducted using comprehensive meta-analysis software. Random-effects model was used to calculate the pooled percentages and means with their 95% confidence intervals (CIs). Sensitivity analysis was performed to assess the effect of individual studies on the summary estimate. A subgroup analysis was conducted according to severity. The main outcomes of the study were to identify the frequency and nature of neurological manifestations and complications, and the neuro-diagnostic findings in COVID-19 patients. Results 44 articles were included with a pooled sample size of 13,480 patients. The mean age was 50.3 years and 53% were males. The most common neurological manifestations were: Myalgia (22.2, 95% CI, 17.2 to 28.1%), taste impairment (19.6, 95% CI, 3.8 to 60.1%), smell impairment (18.3, 95% CI, 15.4 to 76.2%), headache (12.1, 95% CI, 9.1 to 15.8%), dizziness (11.3, 95% CI, 8.5 to 15.0%), and encephalopathy (9.4, 95% CI, 2.8 to 26.6%). Nearly 2.5% (95% CI, 1 to 6.1%) of patients had acute cerebrovascular diseases (CVD). Myalgia, elevated CK and LDH, and acute CVD were significantly more common in severe cases. Moreover, 20 case reports were assessed qualitatively, and their data presented separately. Conclusions Neurological involvement is common in COVID-19 patients. Early recognition and vigilance of such involvement might impact their overall outcomes.

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Neurological Manifestations and Complications of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis

10.21203/rs.3.rs-39952/v1 ◽

2020 ◽

Author(s):

Ahmed Yassin ◽

Mohammed Nawaiseh ◽

Ala' Shaban ◽

Khalid Alsherbini ◽

Khalid El-Salem ◽

...

Keyword(s):

Systematic Review ◽

English Language ◽

Early Recognition ◽

Case Reports ◽

Meta Analysis ◽

Age Groups ◽

Cerebrovascular Diseases ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Summary Estimate

Abstract Background: The spectrum of neurological involvement in COVID-19 is not thoroughly understood. To the best of our knowledge, no systematic review with meta-analysis and a sub-group comparison between severe and non-severe cases has been published. The aim of this study is to assess the frequency of neurological manifestations and complications, identify the neurodiagnostic findings, and compare these aspects between severe and non-severe COVID-19 cases.Methods: A systematic search of PubMed, Scopus, EBSCO, Web of Science, and Google Scholar databases was conducted for studies published between the 1st of January 2020 and 22nd of April 2020. In addition, we scanned the bibliography of included studies to identify other potentially eligible studies. The criteria for eligibility included studies published in English language (or translated to English), those involving patients with COVID-19 of all age groups, and reporting neurological findings. Data were extracted from eligible studies. Meta-analyses were conducted using comprehensive meta-analysis software. Random-effects model was used to calculate the pooled percentages and means with their 95% confidence intervals (CIs). Sensitivity analysis was performed to assess the effect of individual studies on the summary estimate. A subgroup analysis was conducted according to severity. The main outcomes of the study were to identify the frequency and nature of neurological manifestations and complications, and the neuro-diagnostic findings in COVID-19 patients.Results: 44 articles were included with a pooled sample size of 13480 patients. The mean age was 50.3 years and 53% were males. The most common neurological manifestations were: Myalgia (22.2%, 95% CI, 17.2% to 28.1%), taste impairment (19.6%, 95% CI, 3.8% to 60.1%), smell impairment (18.3%, 95% CI, 15.4% to 76.2%), headache (12.1%, 95% CI, 9.1% to 15.8%), dizziness (11.3%, 95% CI, 8.5% to 15.0%), and encephalopathy (9.4%, 95% CI, 2.8% to 26.6%). Nearly 2.5% (95% CI, 1% to 6.1%) of patients had acute cerebrovascular diseases (CVD). Myalgia, elevated CK and LDH, and acute CVD were significantly more common in severe cases. Moreover, 20 case reports were assessed qualitatively, and their data presented separately.Conclusions: Neurological involvement is common in COVID-19 patients. Early recognition and vigilance of such involvement might impact their overall outcomes.

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nCoV-2019 infection induced neurological outcome and manifestation, linking its historical ancestor SARS-CoV and MERS-CoV: a systematic review and meta-analysis

Scientific Reports ◽

10.1038/s41598-021-92188-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ajay Prakash ◽

Harvinder Singh ◽

Phulen Sarma ◽

Anusuya Bhattacharyya ◽

Deba Prasad Dhibar ◽

...

Keyword(s):

Systematic Review ◽

Neurological Outcome ◽

Case Reports ◽

Meta Analysis ◽

Signs And Symptoms ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Cross Sectional ◽

Early Management ◽

Neurological Signs

AbstractThe first systematic review and meta-analysis to help clinician to identify early signs and symptoms of neurological manifestation in COVID-19 positive patients which will further help in early management of patients. Present systematic review and meta-analysis aimed to discuss the prevalence of neurological involvement of the 2019-nCoV patients and assess the symptomatic trend of events as compared to the 2002 “SARS” and 2012 “MERS” pandemics. The articles were systematically screened through several search engine and databases. The articles published or in preprint were included in the study till 15th May 2020. The systematic review done as per the published literatures which included 31 cross sectional, observational studies and case reports which revealed neurological signs and symptoms in SARS-COV-2 disease. For meta-analysis, we included 09 observational and cross-sectional studies which included COVID-19 positive patients and assessed the predominance of various neurological signs and symptoms in COVID-19 patients with relation to SARS-2002 and MERS-2012. Data was analyzed by using the “MedCalc” Statistical Software version 19.2.6 and reported as pooled prevalence. Standard I2 test was used to analyze the heterogeneity. We have collected and screened about a total 2615articles, finally we have included 31articles for the systematic review and 09 for meta-analysis as per the inclusion/exclusion criteria. The analysis was made as per the prevalence rate of neurological symptoms in COVID-19 positive patients. The cumulative neurological outcome of SARS-2002 and MERS-2012 was assessed to get the trends which was further tried to correlate the events with the current pandemic. During the analysis severity and outcome of neurological manifestations range from simple headache to vague non-focal complaints to severe neurologic impairment associated with seizure or meningitis. Central and peripheral nervous system (CNS/PNS) manifestations were seen during the SARS-2002, MERS-2012 and COVID-19. However, none of the publication had primary or secondary objectives of searching neurological manifestations in the COVID-19 patients and the pathogenic mechanism which will subsequently strengthen the importance to start more prospective clinical trials. The prevalence of neurological signs and symptoms were taken as primary objective. Thereafter, the prevalence of each CNS/PNS symptoms was categorized and their prevalence studied. The selection of Bagheri et al., 2020 may be discussed because they have done the cross-sectional study with the neurological finding and correlated the data with prevalence of the COVID-19 positive patients. The proportion of patients presenting with neurological outcome and clinical/PCR positivity were done. We had searched and followed all the possible online/web source, still the data collection process may remain a limitation of work due to addition of several publications on COVID-19 every day. Due to lack of data of SARS-CoV and MERS-CoV, we have included the case reports, MERS and COVID-19 in CNS/PNS manifestations.

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Neurological Manifestations of COVID-19 Associated Multi-system Inflammatory Syndrome in Children: A Systematic Review and Meta-analysis

Journal of Nepal Health Research Council ◽

10.33314/jnhrc.v19i1.3410 ◽

2021 ◽

Vol 19 (1) ◽

pp. 10-18

Author(s):

Gaurav Nepal ◽

Gentle Sunder Shrestha ◽

Jessica Holly Rehrig ◽

Bikram Prasad Gajurel ◽

Rajeev Ojha ◽

...

Keyword(s):

Systematic Review ◽

English Language ◽

Meta Analysis ◽

Signs And Symptoms ◽

Wave Pattern ◽

Neurological Involvement ◽

Neurological Manifestations ◽

Disease Spectrum ◽

Cochrane Database ◽

Inflammatory Syndrome

Background: Children comprise only 1–5% of COVID-19 cases. Recent studies have shown that COVID-19 associated multisystem inflammatory syndrome in children (MIS-C) can present with neurological signs and symptoms. In this systematic review and meta-analysis, we have reviewed neurological involvement in these patients. Methods: A comprehensive electronic literature search was done on PubMed, Google Scholar, Embase, Cochrane database, and SCOPUS for the published English language articles from December 1, 2019, to February 28, 2021. A meta-analysis of the proportion was expressed as a pooled proportion with a 95% confidence interval (CI). Representative forest plots showing individual studies and the combined effect size were generated to provide an overview of the results.Results: This systematic review and meta-analysis analyzed 15 published MIS-C studies with a total of 785 patients. Neurological manifestations in patients with MIS-C was found in 27.1%. We found that 27% developed headaches, 17.1% developed meningism/meningitis and 7.6 % developed encephalopathy. Other uncommon neurological manifestations of MIS-C includes anosmia, seizures, cerebellar ataxia, global proximal muscle weakness and bulbar palsy. In MIS-C patients with neurological feature, neuroimaging showed signal changes in the splenium of the corpus callosum. Electroencephalography showed slow wave pattern and nerve conduction studies and electromyography showed mild myopathic and neuropathic changes. Conclusions: Our study revealed that neurological manifestations are not uncommon in patients with MIS-C. Further large prospective studies are needed to better explore the disease spectrum and to unravel the underlying pathophysiology.Keywords: Children; COVID-19; kawasaki disease; MIS-C, neurology

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Meningoencephalitis associated with COVID-19: A systematic review

10.1101/2020.06.25.20140145 ◽

2020 ◽

Author(s):

Ritwick Mondal ◽

Upasana Ganguly ◽

Shramana Deb ◽

Gourav Shome ◽

Subhasish Pramanik ◽

...

Keyword(s):

Systematic Review ◽

English Language ◽

Final Analysis ◽

Systemic Review ◽

Cochrane Library ◽

Neurological Involvement ◽

P Value ◽

Neurological Manifestations ◽

Medical Subject Headings ◽

Laboratory Findings

AbstractBackground and aimsWith the growing number of COVID-19 cases in recent times, the varied range of presentations is progressively becoming an addressing issue among clinicians. A significant set of patients with extra pulmonary symptoms has been reported worldwide. Neurological involvement in the form of altered mental status, loss of consciousness in considerable amounts has drawn attention of physicians all across the globe. Here we venture out to summarise the clinical profile, investigations and radiological findings among patients with SARS-CoV-2 associated meningoencephalitis in the form of a systematic review, which may aid clinicians in early diagnosis and prognostic evaluation of the disease.MethodologyThis review was carried out based on the existing PRISMA (Preferred Report for Systemic Review and Meta analyses) consensus statement. The data for this review was collected from four databases: Pubmed/Medline, NIH Litcovid, Embase and Cochrane library and Preprint servers up till 10th June, 2020. Search strategy comprised of a range of keywords from relevant medical subject headings which includes “SARS-COV-2”, “COVID-19”, “meningoencephalitis” etc. All peer reviewed, case control, case report, pre print articles satisfying our inclusion criteria were involved in the study. The inclusion prerequisites comprised of confirmed SARS-CoV-2 cases with neurological manifestations, previous cases of SARS-CoV, MERS-CoV with neurological involvement provided all the studies were published in English language. Quantitative data was expressed in mean+/-SD, while the qualitative date in percentages. Paired t test was used for analysing the data based on differences between mean and respective values with a p value of <0.05 considered to be statistically significant.ResultsA total of 43 cases were involved from 24 studies after screening from databases and preprint servers, out of which 29 of them had completed investigation profile and were included in the final analysis. Clincial and Laboratory findings as well as neuroimaging findings (CT, MRI and MRS) revealed consistent presentations towards association of COVID-19 with meningoencephalitis. Epileptogenic pictures were also evident on EEG (electroencephalogram) findings.ConclusionSARS-CoV-2 has been isolated from CSF as well as cerebrum of cases with meningoencephalitis depicting the natural tendency of the virus to invade the central nervous system. Speculations about retrograde olfactory transport or alternative haematogenous spread seem to be correlating with above findings. This review may raise the index of suspicion about COVID-19 among clinicians while attending patients with neurological manifestations.

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Gastrointestinal manifestations of COVID-19 in children: a systematic review and meta-analysis

Frontline Gastroenterology ◽

10.1136/flgastro-2020-101529 ◽

2020 ◽

pp. flgastro-2020-101529 ◽

Cited By ~ 1

Author(s):

Anthony K Akobeng ◽

Ciaran Grafton-Clarke ◽

Ibtihal Abdelgadir ◽

Erica Twum-Barimah ◽

Morris Gordon

Keyword(s):

Systematic Review ◽

English Language ◽

Case Reports ◽

Meta Analysis ◽

Gastrointestinal Symptoms ◽

Case Series ◽

Risk Of Bias ◽

Gastrointestinal Manifestations ◽

Published Evidence ◽

Pooled Prevalence

ObjectivesTo summarise the published evidence on the gastrointestinal manifestations of COVID-19 in children and to determine the prevalence of gastrointestinal symptoms.MethodsIn this systematic review and meta-analysis, we searched PubMed, Embase, CINAHL and the WHO’s database of publications on novel coronavirus. We included English language studies that had described original demographic and clinical characteristics of children diagnosed with COVID-19 and reported on the presence or absence of gastrointestinal symptoms. Meta-analysis was conducted using the random-effects model. The pooled prevalence of gastrointestinal symptoms was expressed as proportion and 95% CI.ResultsThe search identified 269 citations. Thirteen studies (nine case series and four case reports) comprising data for 284 patients were included. Overall, we rated four studies as having a low risk of bias, eight studies as moderate and one study as high risk of bias. In a meta-analysis of nine studies, comprising 280 patients, the pooled prevalence of all gastrointestinal symptoms was 22.8% (95% CI 13.1% to 35.2%; I2=54%). Diarrhoea was the most commonly reported gastrointestinal symptom followed by vomiting and abdominal pain.ConclusionsNearly a quarter of children with COVID-19 have gastrointestinal symptoms. It is important for clinicians to be aware of the gastrointestinal manifestation of COVID-19.PROSPERO registration numberCRD42020177569.

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Effects of underlying morbidities on the occurrence of deaths in COVID-19 patients: A systematic review and meta-analysis

10.1101/2020.05.08.20095968 ◽

2020 ◽

Cited By ~ 2

Author(s):

Mostaured Khan ◽

Md Nuruzzaman Khan ◽

Md. Golam Mustagir ◽

Juwel Rana ◽

Md Saiful Islam ◽

...

Keyword(s):

Systematic Review ◽

Publication Bias ◽

English Language ◽

Meta Analysis ◽

Random Effect ◽

Random Effect Model ◽

Healthcare Providers ◽

Cerebrovascular Diseases ◽

Reference List ◽

Trim And Fill

Abstract Background: Coronavirus disease 2019 (COVID-19), the most hectic pandemic of the era, is increasing exponentially and taking thousands of lives worldwide. This study aimed to assess the prevalence of pre-existing morbidities among COVID-19 infected patients and their mortality risks against each type of pre-existing morbidity category. Methods: To conduct this systematic review and meta-analysis, Medline, Web of Science, Scopus, and CINAHL databases were searched using specified relavent keywords. Further searches were conducted using the reference list of the selected studies, renowned pre-print servers (e.g., medRxiv, bioRixv, SSRN), and relevant journal websites. Studies written in the English language included if those were conducted among COVID-19 patients with and without comorbidities and presented survivor vs. non-survivor counts or hazard/odds of deaths or survivors against types of pre-existing morbidities. Comorbidities reported in the selected studies were grouped into eight categories. The pooled likelihoods of deaths in each category were estimated using a fixed or random-effect model, based on the heterogeneity assessment. Publication bias was assessed by visual inspection of the funnel plot asymmetry and Eggers regression test. Trim and Fill method was used if there any publication bias was found. Results: A total of 42 studies included in this study comprised of 39,398 samples. The most common pre-existing morbidities in COVID-19 infected patients were hypertension (36.5%), cardiovascular disease (11.9%), and diabetes (22.0%). The higher likelihood of deaths was found among COVID-19 patients who had pre-existing cardiovascular diseases (OR: 3.32, 95% CI: 2.79-3.95), immune and metabolic disorders (OR: 2.39, 95% CI: 2.00-2.85), respiratory diseases (OR: 2.02, 95% CI: 1.80-2.26), cerebrovascular diseases (OR: 4.12, 95% CI: 3.04-5.58), any types of cancers (OR: 2.22, 95% CI: 1.63-3.03), renal (OR: 3.02, 95% CI: 2.60-3.52), and liver diseases (OR: 1.44, 95% CI: 1.21-1.71). Conclusions: This study provides evidence of a higher likelihood of deaths among COVID-19 patients against morbidity categories. These findings could potentially help healthcare providers to sort out the most endangered COVID-19 patients by comorbidities, take precautionary measures during hospitalization, assess susceptibility to death, and prioritize their treatment, which could potentially reduce the number of fatalities in COVID-19.

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Factors associated with anorectal Chlamydia trachomatis or Neisseria gonorrhoeae test positivity in women: a systematic review and meta-analysis

Sexually Transmitted Infections ◽

10.1136/sextrans-2018-053950 ◽

2019 ◽

Vol 95 (5) ◽

pp. 361-367 ◽

Cited By ~ 5

Author(s):

Andrew Lau ◽

Fabian Yuh Shiong Kong ◽

Willa Huston ◽

Eric P F Chow ◽

Christopher K Fairley ◽

...

Keyword(s):

Systematic Review ◽

Chlamydia Trachomatis ◽

Neisseria Gonorrhoeae ◽

English Language ◽

Meta Analysis ◽

Prevalence Ratio ◽

Anal Intercourse ◽

Summary Estimate ◽

Language Studies ◽

Meta Analyses

ObjectivesThere has been considerable discussion about anorectal Chlamydia trachomatis (CT) in women, with some calling for anorectal CT screening, but little about anorectal Neisseria gonorrhoeae (NG). Given that urogenital NG is more strongly associated with pelvic inflammatory disease, this is an evidence gap. This systematic review and meta-analysis investigates the associations between anorectal CT in women and CT positivity at other sites (urogenital/oropharyngeal) and with anal intercourse, and compares these with anorectal NG within the same study populations.MethodsElectronic databases were searched for English-language studies published to October 2018 using the following terms: (“Chlamydia” OR “Chlamydia trachomatis”) AND ((“anal” OR “rect*” OR “anorect*”) OR (“extra?genital” OR “multi?site”)). Studies were included if anorectal NG data were available. Random-effects meta-analyses calculated pooled estimates; heterogeneity was investigated using meta-regression.Results25 studies were eligible. Anorectal CT positivity ranged from 0% to 17.5%, with a summary estimate of 8.0% (95% CI 7.0 to 9.1; I2=88.5%). Anorectal NG positivity ranged from 0% to 17.0%, with a summary estimate of 2.1% (95% CI 1.6 to 2.8; I2=92.7%). The association between urogenital and anorectal positivity was stronger for NG than CT (summary prevalence ratio (PR)=89.3 (95% CI 53.1 to 150.3; I2=80.1%), PR=32.2 (95% CI 25.6 to 40.7; I2=70.3%), respectively), and between oropharyngeal and anorectal positivity it was stronger for NG than CT (PR=34.8 (95% CI 10.2 to 118.2; I2=89.9%), PR=8.8 (95% CI 6.8 to 11.5; I2=58.1%), respectively). Anal intercourse was associated with anorectal NG (PR=4.3; 95% CI 2.2 to 8.6; I2=0.0%) but not with anorectal CT (PR=1.0; 95% CI 0.7 to 1.4; I2=0.0%).ConclusionsAnorectal CT is more common than anorectal NG, but anorectal NG is more strongly associated with anal intercourse, urogenital and oropharyngeal NG, suggesting that ongoing discussion about anorectal CT should also include NG. Longitudinal data are required to further understanding of the aetiology of anorectal STIs and assess whether anorectal screening is needed in women.Trial registration numberCRD42df017080188.

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nCoV-2019 infection induces neurological outcome and manifestation, linking its historical ancestor SARS-CoV & MERS-CoV: A systematic review and meta-analysis

10.21203/rs.3.rs-35790/v1 ◽

2020 ◽

Author(s):

Ajay Prakash ◽

Harvinder Singh ◽

Phulen Sarma ◽

Anusuya Bhattacharyya ◽

Deba Prasad Dhibar ◽

...

Keyword(s):

Systematic Review ◽

Neurological Outcome ◽

Case Reports ◽

Meta Analysis ◽

Neurological Manifestation ◽

Neurological Involvement ◽

Cross Sectional ◽

Early Management ◽

Pooled Prevalence ◽

Secondary Objective

Abstract Importance: The first systematic review and meta-analysis to help clinician to identify early the sign and symptoms of neurological manifestation in COVID-19 positive patients which further help in early management of patients. Objective: Present systematic review and meta-analysis aimed to discuss the prevalence of neurological involvement of the 2019-nCoV patients and assess the symptomatic trend of events as compared to the 2002 “SARS” and 2012 “MERS” pandemics.Methods: The articles were systematically screened through several search engine and databases. The articles published or in preprint were included in the study till 15th May 2020. The systematic review done as per the published literatures which included 31 cross sectional, observational studies and case reports which revealed neural sign and symptoms in SARS-COV-2 disease. For meta-analysis, we included 09 observational and cross sectional studies which included COVID-19 positive patients and assessed the predominance of various neurological sign and symptoms in COVID-19 patients relation to SARS-2002 and MERS-2012. Data were analyzed by using the “MedCalc Statistical Software version 19.2.6 and reported as pooled prevalence. Heterogeneity was investigated (standard I2 test). Results: We have collected and screened about a total 2615 articles, finally we have included 31 articles for the systematic review and 09 for meta-analysis as per the inclusion/exclusion criteria. The analysis was made as per the prevalence rate of neurological symptoms during the COVID-19 positive patients. The cumulative neurological outcome of SARS-2002 and MERS-2012 was assessed to get the trends which is next tried to correlate the events with the current pandemic. During the analysis severity and outcome of neurological manifestations range from simple headache to vague non-focal complaints to severe neurologic impairment associated with seizure or meningitis.Conclusion & Relevance: Central and peripheral nervous system (CNS/PNS) manifestations were seen during the SARS-2002, MERS-2012 and COVID-19. However, none of the publication found with the primary or secondary objective of finding the neurological manifestation in the COVID-19 patients and their mechanism which strengthen the importance to start more precise clinical trials.

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Neurological Complications of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-Analysis

Journal of Tropical Pediatrics ◽

10.1093/tropej/fmaa070 ◽

2020 ◽

Cited By ~ 1

Author(s):

Prateek Kumar Panda ◽

Indar Kumar Sharawat ◽

Pragnya Panda ◽

Vivekanand Natarajan ◽

Rahul Bhakat ◽

...

Keyword(s):

Systematic Review ◽

Case Reports ◽

Meta Analysis ◽

Random Effect ◽

Case Series ◽

Neurological Complications ◽

Severe Illness ◽

Neurological Manifestations ◽

Eligibility Criteria ◽

Symptomatic Seizures

Abstract Background Knowledge about neurological complications of COVID-19 in children is limited due to the paucity of data in the existing literature. Some systematic reviews are available describing overall clinical features of COVID-19 in children and neurological complications of COVID-19 in adults. But to the best of our knowledge, no systematic review has been performed to determine neurological manifestations of COVID-19. Methods Six different electronic databases (MEDLINE, EMBASE, Web of Science, CENTRAL, medRxiv and bioRxiv) were searched for articles related to COVID-19 and neurological complications in children. Studies/case series reporting neurological manifestations of COVID-19 in patients aged ≤18 years, as well as case reports, as neurological complications appear to be rare. The pooled estimate of various non-specific and specific neurological manifestations was performed using a random effect meta-analysis. Results Twenty-one studies/case series and five case reports (3707 patients) fulfilled the eligibility criteria and were included in this systematic review, from a total of 460 records. Headache, myalgia and fatigue were predominant non-specific neurological manifestations, presenting altogether in 16.7% cases. Total of 42 children (1%) were found to have been reported with definite neurological complications, more in those suffering from a severe illness (encephalopathy—25, seizure—12, meningeal signs—17). Rare neurological complications were intracranial hemorrhage, cranial nerve palsy, Guillain–Barré syndrome and vision problems. All children with acute symptomatic seizures survived suggesting a favorable short-term prognosis. Conclusion Neurological complications are rare in children suffering from COVID-19. Still, these children are at risk of developing seizures and encephalopathy, more in those suffering from severe illness.

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Association between cytokine levels, sepsis severity and clinical outcomes in sepsis: a quantitative systematic review protocol

BMJ Open ◽

10.1136/bmjopen-2020-048476 ◽

2021 ◽

Vol 11 (8) ◽

pp. e048476

Author(s):

Amal Gharamti ◽

Omar Samara ◽

Anthony Monzon ◽

Sias Scherger ◽

Kristen DeSanto ◽

...

Keyword(s):

Systematic Review ◽

Proinflammatory Cytokines ◽

English Language ◽

Case Reports ◽

Meta Analysis ◽

Interferon Γ ◽

Cochrane Library ◽

Assessment Development ◽

Cytokine Levels ◽

Ethical Approval

IntroductionIt is widely assumed that sepsis is a life-threatening systemic inflammation caused by a dysregulated host response to infection mediated by an increase in multiple proinflammatory cytokines. The levels of key proinflammatory cytokines tumour necrosis factor, interleukin-1β and interferon γ are poorly characterised during sepsis. We believe this project will produce a ‘gold-standard’ document to which other reports on cytokine levels will be compared. The objective of this systematic review will be to identify key cytokine circulating levels in patients with sepsis and assess the association between these levels and morbidity and mortality outcomes related to sepsis.Methods and analysisWe would include reports of any design except for case reports. Sepsis patients will comprise those with a diagnosis of sepsis, severe sepsis or septic shock. The primary exposure is levels of three proinflammatory cytokines. The primary outcome is mortality at 28 or 30 days. Study subjects can be of any age, sex or ethnicity. Studies will be restricted to the English language. Medline, Embase, Cochrane Library and Web of Science Core Collection will be searched for eligible studies. A database search will include studies from 1985 to May 2020. Two reviewers will independently screen and select studies, assess methodological quality and extract data. A meta-analysis will be performed, if possible, and the Grading of Recommendations Assessment Development and Evaluation Summary of Findings presented.Ethics and disseminationFormal ethical approval is not required as data will be extracted from existing literature. This systematic review will be disseminated through a peer-reviewed publication and at conference meetings.PROSPERO registration numberCRD42020179800.

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