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COVID-19, children, cardiovascular, LMICs, systematic review
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Amin MA, Afrin S, Bonna AS et al. Cardiovascular outcomes in children with COVID-19 LMICs: a systematic review and meta-analysis protocol [version 1; peer review: awaiting peer review]. F1000Research 2023, 12:119 (https://doi.org/10.12688/f1000research.129872.1)
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Study Protocol
Cardiovascular outcomes in children with COVID-19 LMICs: a systematic review and meta-analysis protocol
[version 1; peer review: awaiting peer review]
PUBLISHED 01 Feb 2023
OPEN PEER REVIEW
REVIEWER STATUS
This article is included in the Emerging Diseases and Outbreaks gateway.
Abstract
Corresponding author:
Mohammad Ashraful Amin
Competing interests:
No competing interests were disclosed.
Grant information:
The author(s) declared that no grants were involved in supporting this work.
Copyright:
© 2023 Amin MA et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Amin MA, Afrin S, Bonna AS et al. Cardiovascular outcomes in children with COVID-19 LMICs: a systematic review and meta-analysis protocol [version 1; peer review: awaiting peer review]. F1000Research 2023, 12:119 (https://doi.org/10.12688/f1000research.129872.1)
First published: 01 Feb 2023, 12:119 (https://doi.org/10.12688/f1000research.129872.1)
Latest published: 01 Feb 2023, 12:119 (https://doi.org/10.12688/f1000research.129872.1)
Introduction
COVID-19 has spread worldwide and has affected millions of people, impacting many with long-term complications. Worldwide, 63 million people have died from COVID-19 (up until 18 June 2022), and 18 million die annually due to cardiovascular diseases.1,2 Those who survive and recover from COVID-19 may develop short-term or long-term complications. Long-term complications and clinical presentations of COVID-19 can widely vary. There are many pathophysiological mechanisms of COVID-19, but the exact mechanism for long-term complications is still unknown.3 Although COVID-19’s prominent target location is the respiratory tract, the virus can interact with the cardiovascular system to cause myocardial harm via various mechanisms. Complications from COVID-19 in the cardiovascular system can cause myocarditis, arrhythmia, and heart failure.4 People of any age can be affected by COVID-19, which may affect human health for a prolonged time. From the start of the outbreak of COVID-19, children were less affected and developed milder illnesses than adults.
In comparison with adults, there have been few studies of COVID-19 in children, but, whereas adults may experience more severe symptoms from COVID-19, children usually only experience mild issues.5 Despite having a milder clinical course in most instances, some Spanish children in a multicenter national study were found to have acquired a severe illness that required respiratory and hemodynamic care. According to the scant information on pediatric COVID-19 cases, up to 34% of children hospitalized in pediatric intensive care units with COVID-19 also had symptoms of heart malfunction.6 The Centers for Disease Control and Prevention (CDC) reported in March 2020 that, among children aged 0–4 years, 0.3/100000 were hospitalized due to COVID-19, and, among children aged 5–17 years, 0.1/100000 were admitted.4 The Chinese Center for Disease and Control and Prevention reviewed 72,314 COVID-19 patients and found that 1% were children under 10 years of age.7
Previously, cardiovascular disease incidents were significantly higher in high-income countries compared with developing countries.8 Gradually, the incidence of cardiovascular disease has increased significantly in some LMICs, although it is still unknown whether the risk burden of cardiovascular diseases has increased in these countries or not.9 These results show without a doubt that cardiovascular involvement could be a major risk factor in children with COVID-19. Moreover, high-income countries have already showed the importance and threat of cardiovascular involvement in COVID-19 patients.2 However, the cardiovascular involvement in COVID-19 pediatric patients in low- and middle-income countries is yet to be determined. Clinical features can be worsened and severe in children with COVID-19 and can be life-threatening. This systematic study will shed light on the cardiovascular involvement and problems in children with COVID-19, hence helping healthcare providers care better for these children.
Methods
Protocol
The Preferred Reporting Items for Systematic Reviews and Meta-analyses protocols (PRISMA-P) was used to design this study protocol. PRISMA-P includes a 27-item checklist to facilitate the development and reporting of strong protocols for systematic reviews.10 The systematic review was registered on the PROSPERO database CRD42022335384.
Studies will be evaluated according to the eligibility requirements listed below.
Study design
To show COVID-19-related cardiovascular illness in children in LMICs, this systematic review will incorporate cross-sectional, case-control and cohort research.
Setting
There will not be any restrictions on study locations. This evaluation will cover studies that were conducted in clinics, centers for pediatric healthcare, and public settings.
Participants
This study is aimed at children aged 18 years and under from LMICs as defined by the World Bank, regardless of gender, geography, or socioeconomic condition.11,12 Children with active or previous COVID-19 will be included. Children living outside LMICs will be excluded from this analysis.
Inclusion criteria
Original research articles involving the report of the major cardiovascular outcomes previously described in children with COVID-19 or interventional studies which describe their cardiovascular outcomes prevalence, studies with reverse transcription polymerase chain reaction (RT-PCR) for SARS-CoV in children. The reference standard (cohort, clinical trial, and/or case series or case report) is patients swabbed for RT-PCR analysis for confirmation and patients that are free of active disease but who presented in the following year (2019–2022) with any cardiovascular outcomes.
Exclusion criteria
The World Bank’s list of LMICs and studies from industrialized, high-income countries will be excluded. If an article contains data from high-income and low/middle-income countries, only the LMICs will be considered and analyzed. Research involving adults will be excluded. Studies that are published in languages other than English will also not be accepted. No systematic reviews, ongoing trials, trial protocols, current progress evaluations, research communications or correspondences, editorials, review articles, brief reports, journals, textbooks, or book chapters will be considered for inclusion in this review.
Outcomes
Identification of the prevalence of children’s cardiovascular illnesses caused by COVID-19 in LMICs will be the primary outcome of this systematic review. We will include all relevant cardiovascular diseases: heart failure, stroke, cerebrovascular disease, arrhythmia, cardiogenic shock, cardiovascular death, myocarditis, endocarditis, acute coronary syndrome, and thromboembolic events.
Search strategy
The Cochrane Library, Scopus, and MEDLINE (through PubMed) will all be searched online. The chosen databases will be searched using keywords and subject header elements relevant to inclusion and exclusion criteria. The description of the PubMed search method can be found in Supplementary Table 1. In order to find pertinent articles, we will additionally monitor the references of the selected articles. For updates, the search period will be from January 2020 to June 26, 2022. All search results will be posted on the Rayyan software website for additional screening and content selection. Duplicates will be looked for and eliminated from the results.
Data management
The program for reference tracking articles gathered via searches of the literature in various databases will be organized by the Rayyan Qatar Computing Research Institute. In order to create a single library, similar publications will be found, removed from all search results, and consolidated. Reviewers will evaluate the remaining articles.
Selection process
Two unbiased reviewers will separately scan the titles and abstracts of the selected articles to identify those that may include useful analysis based on the inclusion and exclusion criteria. After the title and abstract screening, the potential papers will be assessed. Following that, the shortlisted studies will be further examined for ultimate inclusion. An independent third reviewer will consult with the first two to settle any differences. The PRISMA-P flowchart will demonstrate how studies are included or excluded.13 The stages of article selection will be depicted using a PRISMA-P flow diagram (Figure 1).
Figure 1. The PRISMA-P flow diagram.
Data extraction
Names of authors, study date and location, study type (interventional, observational, case series), absolute population, mean age, female:male ratio, the prevalence of each cardiovascular outcome, and, if not available, indirect estimation through percentages given in the article are examples of the types of data that will be extracted. If there is any doubt about a title’s relevance, it will be included for retrieval.
Risk of bias assessment
Two researchers will evaluate the risk of bias (ROB) independently of the included studies using the Cochrane ROB assessment method.14 To carry out this review, the relevant categories will be used: participant selection, confounding variables, exposure assessment, masking of result evaluations, insufficient outcome data, and biased outcome reporting. The assessors will have thorough discussions to settle any differences. However, if required, a third researcher’s insights will be sought.
Strategy for data synthesis
The outcomes studied will be reported as odds ratios and 95% confidence intervals regarding the prevalence of each cardiovascular outcome. Rare outcomes will be reported as prevalent in the specific population. We will assess study heterogeneity using the Cochrane Chi test and measure study heterogeneity using the I2 statistical test. The P-value of a Chi test greater than 0.05 reveals trial heterogeneity. Low, moderate, and high degrees of heterogeneity are categorized as I2 values below 25%, between 25% and 50%, and above 50%, respectively. In order to look for publishing bias, we will use Review Manager to make a funnel plot (Cochrane). The data gathered for this analysis will be summarized in text and shown in tables.
Discussion
The majority of pediatric COVID-19 fatalities have been reported from LMICs, and the age-specific population used to calculate COVID-19 deaths is higher in LMICs, suggesting that the impact of pediatric COVID-19 fatalities may actually be greater in LMICs than in high-income countries.15 Cardiovascular outcomes may contribute to the greater impact of pediatric COVID-19 fatalities in LMICs. Although numerous observational and interventional primary investigations of cardiovascular outcomes with COVID-19 have been conducted during the last two years,16–19 there has not been any systematic review and meta-analysis of cardiovascular outcomes in children with COVID-19 in LMICs, so studies on this important health issue can provide researchers and policymakers with unique and useful data. All reviews on this topic are vulnerable to heterogeneity due to varied populations, research methods, reviews, and unintentional bias due to non-homogeneous terminology. For researchers who want to construct additional primary or secondary studies on this topic, the findings of this systematic review can assist in explaining the cardiovascular outcome of children with COVID-19 in LMICs. Additionally, it may enhance the internal validity of subsequent evidence.
Strengths and limitations of this study
This thorough investigation advances our knowledge of COVID-19 cardiovascular outcomes in children from underdeveloped nations. Two people with extensive experience using systematic review procedures will separately conduct the vetting of the articles, data retrieval, and quality assessment to minimize the possibility of preconceived views. This study will not explore or use any information that is not in English. This restriction could lead to linguistic bias. We cannot access the “Web of Science” due to access issues.
Ethical approval
The systematic review findings will be published in peer-reviewed journals, presented at conferences, or published in peer-reviewed publications. There is no requirement for ethical approval or patients’ informed consent because aggregated published data will be utilized to alter data about specific individuals.
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how to cite this article
Amin MA, Afrin S, Bonna AS et al. Cardiovascular outcomes in children with COVID-19 LMICs: a systematic review and meta-analysis protocol [version 1; peer review: awaiting peer review] F1000Research 2023, 12:119 (https://doi.org/10.12688/f1000research.129872.1)
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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