Systematic review of cardiac adverse effects in children and young people under 18 years of age after SARS-CoV-2 vaccination

  1. Joana Cruz
  2. Amedine Duret
  3. Rachel Harwood
  4. Lorna K. Fraser
  5. Caroline B. Jones
  6. Joseph Ward
  7. Elizabeth Whittaker
  8. Simon E. Kenny
  9. Russell M. Viner

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Abstract

Background

Reports of myocarditis and pericarditis following vaccination with mRNA vaccines for SARS-CoV-2 have occurred after countries began vaccinating adolescents. We undertook a systematic review of cardiac adverse effects associated with SARS-CoV-2 vaccine in children and young people (CYP)< 18 years.

Methods

Systematic review with protocol prospectively registered with PROSPERO (CRD42021275380).

Six electronic databases were searched from 1 December 2019 to 14 September 2021. Eligible studies were those reporting on CYP with reported or proven myocarditis, pericarditis and/or myopericarditis associated with vaccination against SARS-CoV-2. We summarized findings across all clinical cases reported in case report / case series studies. As a number of studies reported data from two publicly available vaccine surveillance systems, we updated estimates of reporting rates for cardiac adverse events up to 31 October for the US Vaccine Adverse Event Reporting System (VAERS) and 13 November for EudraVigilance covering European Union and European Economic Area (EUEA) countries.

Results

Twenty-one studies were included from 338 identified records. Seventeen were case reports/series describing a total of 127 CYP. Three studies described reporting rates from passive surveillance databases (VAERS, EudraVigilance, and the WHO VigiBase) and one described 22 cases from the US Vaccine Safety Datalink (VSD).

Clinical series reported that 99.2% presented with chest pain, 100% had raised troponin and 73.8% had an abnormal ECG. Cardiovascular magnetic resonance (CMR) in 91 cases identified myocardial injury in 61.5%, with 90.1% showing late gadolinium enhancement. NSAIDs were the most common treatment (76.0%).

One US dataset (VSD) estimated a significant excess of 29.6 events per million vaccine doses across both sexes and doses. There were 1129 reports of myocarditis and 358 reports of pericarditis from across the USA and EU/EEA. The VAERS reporting rate per million for myocarditis was 12.4 for boys and 1.4 for girls after the first dose, and 49.6 for boys and 6.1 for girls after the second dose. There was a marked trend for VAERS reporting to be highest soon after initiation of the vaccine schedule, suggesting reporting bias.

Conclusions

Cardiac adverse effects are very rare after mRNA vaccination for COVID-19 in CYP <18 years. The great majority of cases are mild and self-limiting without significant treatment. No data are yet available on children under 12 years. Larger detailed longitudinal studies are urgently needed from active surveillance sources.

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  1. ScreenIT

    SciScore for 10.1101/2021.12.06.21267339: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Search strategy: We systematically searched PubMed, MedRxiv, Europe PMC, World Health Organisation’s COVID-19 Global Literature on Coronavirus Disease, Research Square and Google Scholar from 1 December 2019 to 14 September 2021 for peer-reviewed papers and reports on cardiac adverse events caused by SARS-CoV-2 immunisation in CYP.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: Our findings are subject to a number of limitations inherent in systematic reviews and in the data sources used. Publication bias towards greater severity is likely amongst the cases reported in the 17 case study/series studies, which may not be representative of the less severe cases. Estimates from vaccine passive surveillance systems such as VAERS and EudraVigilance provide a reporting rate rather than an estimate of excess events, and are crude indicators of risks related to vaccines.61 They cannot attribute causality between vaccine and reported event, lack a comparison group, data quality is highly variable and they are open to a series of biases from over- and -under-reporting.62 VAERS in particular has been criticised as open to over-reporting by those opposed to COVID-19 vaccination.63 64 However all reports are regularly scrutinized to remove duplicate and reports identified as fraudulent, 62 although the extent and timeliness of this is unclear. Passive surveillance systems are most useful for identifying potential safety signals that require further investigation62 through more detailed smaller studies using active systems such as the Vaccine Safety Datalink (VSD). The VSD data included here provide an estimate of excess events, but the VSD can lack power to examine small risks in specific populations25 such as the CYP studied here. Our data focus on 12-17 year olds and should not be regarded as informative for younger children, as very few received C...

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

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  2. Version published to 10.1101/2021.12.06.21267339v1 on medRxiv