Cardiovascular post-acute sequelae of SARS-CoV-2 in children and adolescents: cohort study using electronic health records

Abstract

The risk of cardiovascular outcomes following SARS-CoV-2 infection has been reported in adults, but evidence in children and adolescents is limited. This paper assessed the risk of a multitude of cardiac signs, symptoms, and conditions 28-179 days after infection, with outcomes stratified by the presence of congenital heart defects (CHDs), using electronic health records (EHR) data from 19 children's hospitals and health institutions from the United States within the RECOVER consortium between March 2020 and September 2023. The cohort included 297,920 SARS-CoV-2-positive individuals and 915,402 SARS-CoV-2-negative controls. Every individual had at least a six-month follow-up after cohort entry. Here we show that children and adolescents with prior SARS-CoV-2 infection are at a statistically significant increased risk of various cardiovascular outcomes, including hypertension, ventricular arrhythmias, myocarditis, heart failure, cardiomyopathy, cardiac arrest, thromboembolism, chest pain, and palpitations, compared to uninfected controls. These findings were consistent among patients with and without CHDs. Awareness of the heightened risk of cardiovascular disorders after SARS-CoV-2 infection can lead to timely referrals, diagnostic evaluations, and management to mitigate long-term cardiovascular complications in children and adolescents.

Fig. 1. Selection of individuals for both SARS-CoV-2-positive and SARS-CoV-2-negative patients, stratified by CHD status.

Flowchart illustrating the selection process for SARS-CoV-2-positive and SARS-CoV-2-negative individuals from March 2020 to March 2023, stratified by CHD status. All individuals identified by this process were included after propensity score stratification and therefore included in the analyses. Abbreviation: PASC post-acute sequelae of SARS-CoV-2 infection, PCR polymerase chain reaction, MIS-C multisystem inflammatory syndrome in children, CKD chronic kidney disease, ESKD end-stage kidney disease, CHD congenital heart defects.

Fig. 2. Relative risk (RR) of incident post-acute cardiovascular outcomes compared with the SARS-CoV-2-negative cohort, stratified by CHD status.

Forest plot presenting relative risk (RR) of post-acute cardiovascular outcomes comparing SARS-CoV-2-positive cohort (n = 297,920 patients) with SARS-CoV-2-negative cohort (n = 915,402 patients), stratified by congenital heart defects (CHD) status. Composite outcomes consisted of arrhythmias (atrial fibrillation, ventricular arrhythmias, atrial flutter, 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, deep vein thrombosis, thrombophlebitis, and thromboembolism), cardiovascular-related symptoms (chest pain, palpitations, and syncope), and any cardiovascular outcome (incident occurrence of any cardiovascular outcome studied). The error bars showed the 95% confidence interval (CI) of the estimated RR.

Fig. 3. Subgroup analyses of Relative risk (RR) of incident post-acute composite cardiovascular outcomes compared with the SARS-CoV-2-negative cohort.

Forest plot presenting relative risk (RR) of post-acute cardiovascular outcomes comparing SARS-CoV-2-positive cohort (n = 297,920 patients) with SARS-CoV-2-negative cohort (n = 915,402 patients). The results are stratified according to congenital heart defects (CHD) status, age, race/ethnicity, sex, obesity, severity during the acute phase of COVID-19, and the dominant variant. The error bars showed the 95% confidence interval (CI) of the estimated RR. Source data are provided in Supplementary Table S11. Abbreviation: NHW Non-Hispanic White, NHB Non-Hispanic Black.