Binding and neutralizing antibody responses to SARS-CoV-2 in very young children exceed those in adults

  1. Ruth A. Karron
  2. Maria Garcia Quesada
  3. Elizabeth A. Schappell
  4. Stephen D. Schmidt
  5. Maria Deloria Knoll
  6. Marissa K. Hetrich
  7. Vic Veguilla
  8. Nicole Doria-Rose
  9. Fatimah S. Dawood
  10. SEARCh Study Team

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Abstract

SARS-CoV-2 infections are frequently milder in children than adults, suggesting that immune responses may vary with age. However, information is limited regarding SARS-CoV-2 immune responses in young children.

Methods

We compared receptor binding domain–binding antibody (RBDAb) titers and SARS-CoV-2–neutralizing antibody titers, measured by pseudovirus-neutralizing antibody assay in serum specimens obtained from children aged 0–4 years and 5–17 years and in adults aged 18–62 years at the time of enrollment in a prospective longitudinal household study of SARS-CoV-2 infection.

Results

Among 56 seropositive participants at enrollment, children aged 0–4 years had more than 10-fold higher RBDAb titers than adults (416 vs. 31, P < 0.0001) and the highest RBDAb titers in 11 of 12 households with seropositive children and adults. Children aged 0–4 years had only 2-fold higher neutralizing antibody than adults, resulting in higher binding-to-neutralizing antibody ratios compared with adults (2.36 vs. 0.35 for ID 50 , P = 0.0004).

Conclusion

These findings suggest that young children mount robust antibody responses to SARS-CoV-2 following community infections. Additionally, these results support using neutralizing antibody to measure the immunogenicity of COVID-19 vaccines in children aged 0–4 years.

Funding

CDC (award 75D30120C08737).

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  1. Version published to 10.1172/jci.insight.157963
  2. ScreenIT

    SciScore for 10.1101/2021.12.20.21268034: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Prior to study participation, all participants or their parents/guardians provided informed consent, and children aged 7 years and older also provided assent.
    IRB: The study protocol was reviewed and approved by the Johns Hopkins Bloomberg School of Public Health Institutional Review Board (IRB).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Data were collected using Research Electronic Data Capture (REDCap).
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    Statistical analysis: Analyses were performed using Graphpad Prism (San Diego, CA) and in R version .
    Graphpad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    1.0 (R Foundation for Statistical Computing) in RStudio version 1.4.1717 (RStudio, Inc).
    RStudio
    suggested: (RStudio, RRID:SCR_000432)
    Figures were generated using Graphpad Prism and the Ggplot2 package.
    Ggplot2
    suggested: (ggplot2, RRID:SCR_014601)

    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: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    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.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  3. Version published to 10.1101/2021.12.20.21268034 on medRxiv