Review 2: "Post-Acute Cardiovascular Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Project"

RR\ID Evidence Scale rating by reviewer:

• Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review: The results and conclusions presented are well-supported by the evidence provided. The study has limitations, which are acknowledged and minimized as much as possible, and these limitations do not alter the main claims of the study. The evidence provided is robust enough to consider its main claims actionable.

The study’s findings confirm and expand existing knowledge about the long-term effects of COVID-19 on cardiovascular health, particularly in the pediatric population. It demonstrates that children and adolescents infected with SARS-CoV-2 face a significantly increased risk of post-COVID cardiovascular events. These findings align with previous studies that identified a higher prevalence of myocarditis, arrhythmias, and other cardiovascular complications, reinforcing the idea that COVID-19 has persistent cardiovascular effects not only in adults but also in children and adolescents.

By including a large cohort of pediatric patients, the study offers valuable evidence in an underexplored area: the post-COVID cardiovascular effects in children and adolescents. The study also includes subgroup analyses based on age, race/ethnicity, obesity, gender, and COVID-19 severity, providing a deeper understanding of how COVID-19 affects different groups within the pediatric population. This enriches knowledge on the long-term sequelae of COVID-19 in young people.

The findings have important implications for both public and scientific understanding of the long-term effects of COVID-19, particularly for the pediatric population. These results could influence clinical follow-up protocols and public health policies related to cardiovascular monitoring in individuals under 21 who have had COVID-19.

The study is well-positioned within the current literature, referencing prior research that has identified cardiovascular risks associated with COVID-19 in both adults and children. What sets this study apart is its large sample size, which includes a significant pediatric population, long-term follow-up, and a diverse set of healthcare settings (primary, specialty, and emergency care, along with testing and inpatient facilities). Furthermore, the analysis incorporates congenital heart disease (CHD) as a key variable, improving the precision of the findings given its prevalence as the most common congenital disorder in pediatrics.

The manuscript also appropriately discusses the limitations of the data, such as potential biases from the use of diagnostic codes without clinical validation and the lack of information on vaccinations and reinfections. It is also noted that the frequency of hospital visits by COVID-19 patients could potentially bias the observed post-acute cardiovascular outcomes upward, as these patients may visit hospitals more frequently. These limitations are clearly addressed, with efforts made to minimize their impact.

The results are relevant for the development of public health policies, as post-COVID cardiovascular effects in children may not be immediately apparent but could have long-term consequences. This study is crucial for designing cardiovascular monitoring programs for the pediatric population in the post-pandemic era. 

The manuscript is well-structured, presenting results clearly and logically, addressing both the findings and their implications. It is written in a manner that can be understood by healthcare professionals, public health officials, and the general public interested in the long-term effects of COVID-19. Additionally, the study provides a detailed description of the methods used, which could help researchers replicate or extend these findings.

The study acknowledges diversity and equity by analyzing the effects of COVID-19 on different racial/ethnic groups and examining variations in risk based on gender and obesity. 

The authors’ analysis of sociodemographic factors emphasizes the importance of providing equitable and personalized healthcare based on the needs of each group.