Seropositivity to Nucleoprotein to detect mild and asymptomatic SARS-CoV-2 infections: A complementary tool to detect breakthrough infections after COVID-19 vaccination?

  1. Lotus L. van den Hoogen
  2. Gaby Smits
  3. Cheyenne C.E. van Hagen
  4. Denise Wong
  5. Eric R.A. Vos
  6. Michiel van Boven
  7. Hester E. de Melker
  8. Jeffrey van Vliet
  9. Marjan Kuijer
  10. Linde Woudstra
  11. Alienke J. Wijmenga-Monsuur
  12. Corine H. GeurtsvanKessel
  13. Susanne P. Stoof
  14. Daphne Reukers
  15. Lisa A. Wijsman
  16. Adam Meijer
  17. Chantal B.E.M. Reusken
  18. Nynke Y. Rots
  19. Fiona R.M. van der Klis
  20. Robert S. van Binnendijk
  21. Gerco den Hartog

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Abstract

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  1. Version published to 10.1016/j.vaccine.2022.03.009
  2. ScreenIT

    SciScore for 10.1101/2021.10.05.21264555: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study was ethically approved by the Medical-Ethical Review Committee of the University Medical Center Utrecht (NL13529.041.06).
    Consent: All participants above the age of 12 gave written informed consent.
    Field Sample Permit: The study was ethically approved by the Medical Research Ethics Committees United MEC-U and registered under trial number NL8473.
    Sex as a biological variablenot detected.
    RandomizationParticipants from the PIENTER-3 study who had consented to follow-up were invited to participate in the PICO study in April 2020 [14] and the cohort was extended with an additional nationwide random sample in June 2020 [15].
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Median fluorescence intensity measurements were expressed as binding antibody units per milliliter (BAU/ml) using 5-parameter logistic interpolation of the International Standard for human anti-SARS-CoV-2 immunoglobulin (20/136 NIBSC standard) [18].
    anti-SARS-CoV-2 immunoglobulin
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Briefly, the PICO study emanated from a large-scale nationwide cross-sectional study performed in 2016-17 (PIENTER-3 [16]).
    PIENTER-3
    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:
    There are strengths and weaknesses in the cohorts we used in this study. Study team nurses collecting samples and questionnaire data at pre-set sampling timepoints is the strength of the household cohort, but its weakness includes that results are likely to correlate within families (i.e., genetic relatedness and immune response). The national cohort is more representative of the general population, including more asymptomatic individuals, and the repeated cross-sectional design ensured that participants were included with different time frames since infection and/or vaccination. However, the weakness of this approach is that it relied on self-reported data. Several types of bias may arise from self-reported data including recall bias, e.g. those who tested SARS-CoV-2 positive might be more likely to remember the type of symptoms or test they received. In conclusion, we showed that Nucleoprotein can detect prior SARS-CoV-2 infections with a sensitivity of 85% in a mildly symptomatic unvaccinated population between two weeks and two months after symptom onset. Serological responses to Nucleoprotein may thus prove helpful in identifying the frequency of SARS-CoV-2 infections in vaccinated persons, alongside molecular tests. Furthermore, it can help to interpret IgG to Spike S1 responses after COVID-19 vaccination as particularly high responses shortly after vaccination could be explained by prior exposure history.

    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.

  3. Version published to 10.1101/2021.10.05.21264555 on medRxiv