The SARS-CoV-2 antibody landscape is lower in magnitude for structural proteins, diversified for accessory proteins and stable long-term in children

  1. Asmaa Hachim
  2. Haogao Gu
  3. Otared Kavian
  4. Mike YW Kwan
  5. Wai-hung Chan
  6. Yat Sun Yau
  7. Susan S Chiu
  8. Owen TY Tsang
  9. David SC Hui
  10. Fionn Ma
  11. Eric HY Lau
  12. Samuel MS Cheng
  13. Leo LM Poon
  14. JS Malik Peiris
  15. Sophie A Valkenburg
  16. Niloufar Kavian

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Abstract

Background

Children are less clinically affected by SARS-CoV-2 infection than adults with the majority of cases being mild or asymptomatic and the differences in infection outcomes are poorly understood. The kinetics, magnitude and landscape of the antibody response may impact the clinical severity and serological diagnosis of COVID-19. Thus, a comprehensive investigation of the antibody landscape in children and adults is needed.

Methods

We tested 254 plasma from 122 children with symptomatic and asymptomatic SARS-CoV-2 infections in Hong Kong up to 206 days post symptom onset, including 146 longitudinal samples from 58 children. Adult COVID-19 patients and pre-pandemic controls were included for comparison. We assessed antibodies to a 14-wide panel of SARS-CoV-2 structural and accessory proteins by Luciferase Immunoprecipitation System (LIPS).

Findings

Children have lower levels of Spike and Nucleocapsid antibodies than adults, and their cumulative humoral response is more expanded to accessory proteins (NSP1 and Open Reading Frames (ORFs)). Sensitive serology using the three N, ORF3b, ORF8 antibodies can discriminate COVID-19 in children. Principal component analysis revealed distinct serological signatures in children and the highest contribution to variance were responses to non-structural proteins ORF3b, NSP1, ORF7a and ORF8. Longitudinal sampling revealed maintenance or increase of antibodies for at least 6 months, except for ORF7b antibodies which showed decline. It was interesting to note that children have higher antibody responses towards known IFN antagonists: ORF3b, ORF6 and ORF7a. The diversified SARS-CoV-2 antibody response in children may be an important factor in driving control of SARS-CoV-2 infection.

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  1. ScreenIT

    SciScore for 10.1101/2021.01.03.21249180: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIRB: The COVID-19 patient study was approved by the institutional review board of the respective hospitals, viz.
    Consent: All of patients provided informed consent.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    SARS-CoV-2 cloning and (Ruc)-antigen expression: Based on previous studies describing the structure of the SARS-CoV-2 genome25,36, an extensive panel of 14 proteins (S1, S2, S2’, E, M, N, NSP1, ORF3a, 3b, 6, 7a, 7b, 8, 10) was chosen for antibody testing by LIPS.
    S1
    suggested: None
    NSP1
    suggested: None
    Clusters of points: The SARS-CoV-2 antibodies dataset has been treated through the free software ConTeXt, with LuaMetaTeXengine (version 2020.05.18) developed by Hans Hagen (http://www.pragma-ade.nl) which uses TeX, Metapost and Lua to obtain the 3D clusters of points shown in Figure 3abc, Figure 7c and Supplemental Figure 2.
    SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    The completed data were standardized (scaled) before input in standard PCA (using FactoMineR (version 2.4)39..
    FactoMineR
    suggested: (FactoMineR, RRID:SCR_014602)
    Statistics and Reproducibility: GraphPad Prism version 8 software (San Diego, CA) was used for statistical analysis.
    Reproducibility: GraphPad Prism
    suggested: None
    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: 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.

    About SciScore

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  2. Version published to 10.1101/2021.01.03.21249180v1 on medRxiv
  3. Version published to 10.1101/2021.01.03.21249180v2 on medRxiv