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

  1. Bingyu Zhang
  2. Deepika Thacker
  3. Ting Zhou
  4. Dazheng Zhang
  5. Yuqing Lei
  6. Jiajie Chen
  7. Elizabeth Chrischilles
  8. Dimitri A. Christakis
  9. Soledad Fernandez
  10. Vidu Garg
  11. Susan Kim
  12. Abu S. M. Mosa
  13. Marion R. Sills
  14. Bradley W. Taylor
  15. David A. Williams
  16. Qiong Wu
  17. Christopher B. Forrest
  18. Yong Chen

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Abstract

Background

The risk of cardiovascular outcomes in the post-acute phase of SARS-CoV-2 infection has been quantified among adults and children. This paper aimed to assess a multitude of cardiac signs, symptoms, and conditions, as well as focused on patients with and without congenital heart defects (CHDs), to provide a more comprehensive assessment of the post-acute cardiovascular outcomes among children and adolescents after COVID-19.

Methods

This retrospective cohort study used data from the RECOVER consortium comprising 19 US children’s hospitals and health institutions between March 2020 and September 2023. Every participant had at least a six-month follow-up after cohort entry. Absolute risks of incident post-acute COVID-19 sequelae were reported. Relative risks (RRs) were calculated by contrasting COVID-19-positive with COVID-19-negative groups using a Poisson regression model, adjusting for demographic, clinical, and healthcare utilization factors through propensity scoring stratification.

Results

A total of 1,213,322 individuals under 21 years old (mean[SD] age, 7.75[6.11] years; 623,806 male [51.4%]) were included. The absolute rate of any post-acute cardiovascular outcome in this study was 2.32% in COVID-19 positive and 1.38% in negative groups. Patients with CHD post-SARS-CoV-2 infection showed increased risks of any cardiovascular outcome (RR, 1.63; 95% confidence interval (CI), 1.47-1.80), including increased risks of 11 of 18 post-acute sequelae in hypertension, arrhythmias (atrial fibrillation and ventricular arrhythmias), myocarditis, other cardiac disorders (heart failure, cardiomyopathy, and cardiac arrest), thrombotic disorders (thrombophlebitis and thromboembolism), and cardiovascular-related symptoms (chest pain and palpitations). Those without CHDs also experienced heightened cardiovascular risks after SARS-CoV-2 infection (RR, 1.63; 95% CI, 1.57-1.69), covering 14 of 18 conditions in hypertension, arrhythmias (ventricular arrhythmias and premature atrial or ventricular contractions), inflammatory heart disease (pericarditis and myocarditis), other cardiac disorders (heart failure, cardiomyopathy, cardiac arrest, and cardiogenic shock), thrombotic disorders (pulmonary embolism and thromboembolism), and cardiovascular-related symptoms (chest pain, palpitations, and syncope).

Conclusions

Both children with and without CHDs showed increased risks for a variety of cardiovascular outcomes after SARS-CoV-2 infection, underscoring the need for targeted monitoring and management in the post-acute phase.

Clinical Perspective section

What is new?

  • We investigated the risks of 18 post-acute COVID-19 cardiovascular outcomes in the pediatric population without Multisystem Inflammatory Syndrome in Children (MIS-C) in over 1 million patients, stratified by congenital heart defects (CHD) status.

  • We extended the follow-up period beyond previous pediatric studies, ensuring every participant had at least a six-month follow-up after cohort entry.

  • We included a comprehensive cross-section of the US pediatric population across various healthcare settings including primary, specialty, and emergency care, as well as testing and inpatient facilities.

What are the clinical implications?

  • Within the post-acute phase, children and adolescents previously infected with SARS-CoV-2 are at statistically significant increased risk of incident cardiovascular outcomes, including hypertension, ventricular arrhythmias, myocarditis, heart failure, cardiomyopathy, cardiac arrest, thromboembolism, chest pain, and palpitations. These findings are consistent among patients with and without CHDs.

  • Awareness of the heightened risk of cardiovascular disorders after COVID-19 can lead to a timely referral, investigations, and management of these conditions in children and adolescents.

Article activity feed

  1. Rapid Reviews Infectious Diseases

    Manuel Narro, Cyntia Ibanes-Gutiérrez

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

    Reviewers highlighted the study’s strengths, including its large, diverse cohort and detailed subgroup analysis, but recommended clarifying the criteria for confirmed COVID-19 diagnoses and including a discussion on how findings might support pediatric vaccination.

  2. Rapid Reviews Infectious Diseases

    Diana Vilar-Compte

    Review 1: "Post-Acute Cardiovascular Outcomes of COVID-19 in Children and Adolescents: An EHR Cohort Study from the RECOVER Project"

    Reviewers highlighted the study’s strengths, including its large, diverse cohort and detailed subgroup analysis, but recommended clarifying the criteria for confirmed COVID-19 diagnoses and including a discussion on how findings might support pediatric vaccination.

  4. Version published to 10.1101/2024.05.14.24307380v1 on medRxiv