Dynamics of infection-elicited SARS-CoV-2 antibodies in children over time

  1. Lauren E. Gentles
  2. Leanne Kehoe
  3. Katharine H.D. Crawford
  4. Kirsten Lacombe
  5. Jane Dickerson
  6. Caitlin Wolf
  7. Joanna Yuan
  8. Susanna Schuler
  9. John T. Watson
  10. Sankan Nyanseor
  11. Melissa Briggs-Hagen
  12. Sharon Saydah
  13. Claire M. Midgley
  14. Kimberly Pringle
  15. Helen Chu
  16. Jesse D. Bloom
  17. Janet A. Englund

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits an antibody response that targets several viral proteins including spike (S) and nucleocapsid (N); S is the major target of neutralizing antibodies. Here, we assess levels of anti-N binding antibodies and anti-S neutralizing antibodies in unvaccinated children compared with unvaccinated older adults following infection. Specifically, we examine neutralization and anti-N binding by sera collected up to 52 weeks following SARS-CoV-2 infection in children and compare these to a cohort of adults, including older adults, most of whom had mild infections that did not require hospitalization. Neutralizing antibody titers were lower in children than adults early after infection, but by 6 months titers were similar between age groups. The neutralizing activity of the children’s sera decreased modestly from one to six months; a pattern that was not significantly different from that observed in adults. However, infection of children induced much lower levels of anti-N antibodies than in adults, and levels of these anti-N antibodies decreased more rapidly in children than in adults, including older adults. These results highlight age-related differences in the antibody responses to SARS-CoV-2 proteins and, as vaccines for children are introduced, may provide comparator data for the longevity of infection-elicited and vaccination-induced neutralizing antibody responses.

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  1. ScreenIT

    SciScore for 10.1101/2022.01.14.22269235: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Informed consent was obtained from parents and assent from children over 7 years of age.
    Field Sample Permit: Blood specimens were immediately added to acid citrate dextrose tubes upon collection which were then spun down to separate out the red blood cell fraction.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-N IgG index values were assessed; higher index values reflected higher antibody levels.
    Anti-N IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    To perform neutralization assays, 1.25x104 HEK-293T-ACE2 cells (39) (BEI resources NR-52511) are added in 50ul per well of a 96-well poly-L-lysine coated plate (Greiner; no. 655936).
    HEK-293T-ACE2
    suggested: None
    Software and Algorithms
    SentencesResources
    NT50 values were calculated using the neutcurve python package version 0.5.3 available here: https://github.com/jbloomlab/neutcurve which fit a Hill curve to our data to determine the 50% inhibitory concentration (IC50).
    python
    suggested: (IPython, RRID:SCR_001658)
    SARS-CoV-2 IgG assay: The SARS-CoV-2 IgG assay, an FDA Emergency Use Authorized immunoassay, which utilizes a chemiluminescent test to assess immunoglobulin G (IgG) binding to nucleocapsid (N) protein, was performed according to manufacturer specifications (Abbott)
    Abbott
    suggested: (Abbott, RRID:SCR_010477)

    Results from OddPub: Thank you for sharing your code and data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations of our study include small sample size, a limited number of children with follow-up at 52-weeks, and differences in the sex distribution between the pediatric and adult cohorts. Follow-up is ongoing with children who had not yet reached 52-weeks post-symptom onset at the time of this analysis. Furthermore, blood volume obtained from younger children is limited and therefore the number of assays utilized was also limited. The adult comparative specimens were obtained from the same geographic location and analyzed in the same laboratory, although not necessarily collected from the same families or at the same time. The adult specimens were also plasma, whereas the pediatric specimens were serum, and the differences in collection and storage of these could possibly result in slight differences in antibody concentrations. Additionally, the adults in this study were a convenience sample of a broader study, and approximately half were older adults, over 65 years of age, meaning that the data presented here may not be representative of all adults across wider age ranges. Likewise, our pediatric cohort was also a convenience sample and may also not be representative of the broader population. Furthermore, unlike the pediatric cohort, adults were only enrolled following RT-PCR confirmed infection without enrollment based on household RT-PCR positive contacts. Of note, both children and adult cohorts were enrolled prior to the widespread introduction of the SARS-CoV-2 Delta...

    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.
    • Thank you for including a protocol registration statement.

    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.

  2. Version published to 10.1101/2022.01.14.22269235v1 on medRxiv