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.

To show COVID-19-related cardiovascular illness in children in LMICs, this systematic review will incorporate cross-sectional, case-control and cohort research.

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.

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.

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.

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.

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.

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.

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.

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).

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.

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.

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 I ² 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 I ² 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.

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.