Asymptomatic or mild symptomatic SARS-CoV-2 infection elicits durable neutralizing antibody responses in children and adolescents

  1. Carolina Garrido
  2. Jillian H. Hurst
  3. Cynthia G. Lorang
  4. Jhoanna N. Aquino
  5. Javier Rodriguez
  6. Trevor S. Pfeiffer
  7. Tulika Singh
  8. Eleanor C. Semmes
  9. Debra J. Lugo
  10. Alexandre T. Rotta
  11. Nicholas A. Turner
  12. Thomas W. Burke
  13. Micah T. McClain
  14. Elizabeth A. Petzold
  15. Sallie R. Permar
  16. M. Anthony Moody
  17. Christopher W. Woods
  18. Matthew S. Kelly
  19. Genevieve G. Fouda

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Abstract

No abstract available

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  1. Version published to 10.1172/jci.insight.150909
  2. ScreenIT

    SciScore for 10.1101/2021.04.17.21255663: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the DUHS Institutional Review Board.
    Consent: Informed consent was obtained from all study participants or their legal guardians, with written approval obtained using an electronic consent document.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Measurement of serum SARS-CoV-2-specific antibodies: We measured serum antibodies using a customized binding antibody multiplex assay to the following SARS-CoV-2 antigens: whole spike (S), subunit 1 (S1), subunit 2 (S2), receptor binding domain (RBD),
    , subunit 1 ( S1) , subunit 2 ( S2) , receptor binding domain ( RBD) ,
    suggested: None
    Antibody binding to the bead-coupled antigens was then detected with phycoerythrin (PE)-conjugated mouse anti-human IgG, IgM or IgA (Southern Biotech) at 2 μg/ml, using a Bio-Plex 200 instrument (Bio-Rad Laboratories), which rendered a mean fluorescent intensity (MFI) for each sample.
    anti-human IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    SARS-CoV-2 Pseudovirus Neutralization Assays: SARS-CoV-2 neutralization was measured with spike-pseudotyped viruses in HEK-293T-hACE2 cells as a function of reduction in luciferase (Luc) reporter activity.
    HEK-293T-hACE2
    suggested: None
    Pseudovirions were produced in HEK 293T/17 cells (ATCC) by using FuGene 6 (Promega) and co-transfecting spike plasmid, lentiviral backbone plasmid (pCMV ΔR8.2), a firefly luciferase reporter gene plasmid (pHR’ CMV Luc) [1], and a plasmid containing TMPRSS2 (required for cell entry).
    HEK 293T/17
    suggested: ATCC Cat# CRL-11268, RRID:CVCL_1926)
    Recombinant DNA
    SentencesResources
    Pseudovirions were produced in HEK 293T/17 cells (ATCC) by using FuGene 6 (Promega) and co-transfecting spike plasmid, lentiviral backbone plasmid (pCMV ΔR8.2), a firefly luciferase reporter gene plasmid (pHR’ CMV Luc) [1], and a plasmid containing TMPRSS2 (required for cell entry).
    pCMV ΔR8.2
    suggested: None
    Software and Algorithms
    SentencesResources
    43 Study data were managed using REDCap electronic data capture tools hosted at Duke University.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    44 Analyses were performed using GraphPad Prism (GraphPad Software, Inc., CA, US) and R version 4.0.3.45
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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:
    Our study has several limitations. First, we focused on pediatric and adult populations with asymptomatic and mild infections, but did not include participants with severe COVID-19 or children with MIS-C; thus, our findings are generalizable only to individuals with asymptomatic or mild symptomatic SARS-CoV-2 infection. Second, we did not evaluate cellular immunity, which is likely required for long-term immunological memory.3 Third, while several studies in adults have measured antibody responses out to 8 months after acute infection, we currently only have data for children and adolescents up to 4 months after infection. Finally, additional studies will be needed to assess the impact of emerging SARS-CoV-2 variants on viral-specific immune responses in children and adolescents and define if immune responses induced by prior infections are able to protect against these variants. In conclusion, we found that children and adolescents with asymptomatic or mild symptomatic SARS-CoV-2 infection mount broad, effective, and durable antibody responses that exhibit robust viral neutralizing activity at least 4 months after acute infection. Notably, these responses were largely similar or superior to those observed in adults with symptomatic SARS-CoV-2 infection who did not require hospitalization. Our findings suggest that children and adolescents develop effective humoral immune responses irrespective of illness severity that are likely to provide protection against reinfection, the...

    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.

    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 10.1101/2021.04.17.21255663 on medRxiv