Robust and durable serological response following pediatric SARS-CoV-2 infection

  1. Hanna Renk
  2. Alex Dulovic
  3. Alina Seidel
  4. Matthias Becker
  5. Dorit Fabricius
  6. Maria Zernickel
  7. Daniel Junker
  8. Rüdiger Groß
  9. Janis Müller
  10. Alexander Hilger
  11. Sebastian F. N. Bode
  12. Linus Fritsch
  13. Pauline Frieh
  14. Anneke Haddad
  15. Tessa Görne
  16. Jonathan Remppis
  17. Tina Ganzemueller
  18. Andrea Dietz
  19. Daniela Huzly
  20. Hartmut Hengel
  21. Klaus Kaier
  22. Susanne Weber
  23. Eva-Maria Jacobsen
  24. Philipp D. Kaiser
  25. Bjoern Traenkle
  26. Ulrich Rothbauer
  27. Maximilian Stich
  28. Burkhard Tönshoff
  29. Georg F. Hoffmann
  30. Barbara Müller
  31. Carolin Ludwig
  32. Bernd Jahrsdörfer
  33. Hubert Schrezenmeier
  34. Andreas Peter
  35. Sebastian Hörber
  36. Thomas Iftner
  37. Jan Münch
  38. Thomas Stamminger
  39. Hans-Jürgen Groß
  40. Martin Wolkewitz
  41. Corinna Engel
  42. Weimin Liu
  43. Marta Rizzi
  44. Beatrice H. Hahn
  45. Philipp Henneke
  46. Axel R. Franz
  47. Klaus-Michael Debatin
  48. Nicole Schneiderhan-Marra
  49. Ales Janda
  50. Roland Elling

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Abstract

The quality and persistence of children’s humoral immune response following SARS-CoV-2 infection remains largely unknown but will be crucial to guide pediatric SARS-CoV-2 vaccination programs. Here, we examine 548 children and 717 adults within 328 households with at least one member with a previous laboratory-confirmed SARS-CoV-2 infection. We assess serological response at 3–4 months and 11–12 months after infection using a bead-based multiplex immunoassay for 23 human coronavirus antigens including SARS-CoV-2 and its Variants of Concern (VOC) and endemic human coronaviruses (HCoVs), and additionally by three commercial SARS-CoV-2 antibody assays. Neutralization against wild type SARS-CoV-2 and the Delta VOC are analysed in a pseudotyped virus assay. Children, compared to adults, are five times more likely to be asymptomatic, and have higher specific antibody levels which persist longer (96.2% versus 82.9% still seropositive 11–12 months post infection). Of note, symptomatic and asymptomatic infections induce similar humoral responses in all age groups. SARS-CoV-2 infection occurs independent of HCoV serostatus. Neutralization responses of children and adults are similar, although neutralization is reduced for both against the Delta VOC. Overall, the long-term humoral immune response to SARS-CoV-2 infection in children is of longer duration than in adults even after asymptomatic infection.

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  1. Version published to 10.1038/s41467-021-27595-9
  2. ScreenIT

    SciScore for 10.1101/2021.07.20.21260863: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics approval was obtained from the respective Medical Faculties’ independent ethics committees (University of Freiburg: 256/20_201553; University of Tübingen: 293/2020BO2; University of Ulm: 152/20).
    Consent: Written informed consent was obtained from adult participants and from parents or legal guardians on behalf of their children at both sampling time points.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Serological assays: Antibodies against SARS-CoV-2 in 2236 samples were detected using the following four assays: (1) EuroImmun-Anti-SARS-CoV-2 ELISA IgG and IgA (S1), (2) Siemens Healthineers SARS-CoV-2 IgG (RBD), (3) Roche Elecsys Ig (N) and (4) MULTICOV-AB, a previously published bead-based multiplex immunoassay that simultaneously analyses antibody binding to 23 antigens from SARS-CoV-2 (including VOCs)20,21.
    EuroImmun-Anti-SARS-CoV-2 ELISA IgG
    suggested: None
    IgA (S1), (2
    suggested: None
    The MULTICOV-AB assay also analyses antibody binding to endemic coronavirus antigens (i.e. HCoV-OC43, - NL63, -HKU1 and -229E)20,21. 385 samples were analyzed with the GenScript SARS-CoV-2 Surrogate Virus Neutralization Test (sVNT).
    NL63
    suggested: (Virostat Cat# 3879, RRID:AB_2889994)
    -HKU1
    suggested: None

    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 of our study include the potential recall-bias inherent to retrospective self- or parent-reporting of symptoms via questionnaires and physician-interviews. Additionally, PCR tests for SARS-CoV-2 during the first wave in Germany were mostly limited to the household index case, meaning it is possible that infected individuals were not identified as such, despite the multi-assay serological approach. However, the in-depth characterization of the humoral response provides valuable data for clinicians, public health officials and the public, at a time when children are increasingly viewed as a potential viral reservoir due to exclusion of pediatric populations from current vaccination strategies. Similarly, while PCR testing was not available for all individuals, the strength of this cohort comes from the comparatively large number of children, inclusion of children and adults from the same household, the inclusion of seronegative household members as well-matched controls, and the prospective longitudinal analysis of the humoral response in children for up to one year post-infection. The seropositive cohort also comprises almost exclusively individuals with mild or asymptomatic infections and so provides real-world data representative for the majority of SARS-CoV-2 infections in the community. In summary, although children mostly show mild or even asymptomatic clinical courses following SARS-CoV-2 infection, they mount a strong and enduring humoral immune response. Th...

    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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  3. Version published to 10.1101/2021.07.20.21260863v1 on medRxiv