Three Separate Spike Antigen Exposures by COVID-19 Vaccination or SARS-CoV-2 Infection Elicit Strong Humoral Immune Responses in Healthcare Workers

  1. Thomas Theo Brehm
  2. Felix Ullrich
  3. Michelle Thompson
  4. Julia Küchen
  5. Dorothee Schwinge
  6. Anthea Spier
  7. Samuel Huber
  8. Johannes K. Knobloch
  9. Martin Aepfelbacher
  10. Marylyn M. Addo
  11. Ansgar W. Lohse
  12. Marc Lütgehetmann
  13. Julian Schulze zur Wiesch

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Abstract

Background: The immunogenicity of different COVID-19 vaccine regimens and combinations in naïve and convalescent individuals has not been formally tested in controlled studies, and real-life observational studies are scarce. Methods: We assessed the SARS-CoV-2 infection and COVID-19 vaccination-induced immunity of 697 hospital workers at the University Medical Center Hamburg-Eppendorf between 17 and 31 January 2022. Results: The overall prevalence of anti-NC-SARS-CoV-2 antibodies indicating prior infection was 9.8% (n = 68) and thus lower than the seroprevalence in the general population. All vaccinated individuals had detectable anti-S1-RBD-SARS-CoV-2 antibodies (median AU/mL [IQR]: 13,891 [8505–23,543]), indicating strong protection against severe COVID-19. Individuals who received three COVID-19 vaccine doses (median AU/mL [IQR]: 13,856 [8635–22,705]) and those who resolved a prior SARS-CoV-2 infection and had received two COVID-19 vaccine doses (median AU/mL [IQR] 13,409 [6934–25,000]) exhibited the strongest humoral immune responses. Conclusions: The current study indicates that three exposures to the viral spike protein by either SARS-CoV-2 infection or COVID-19 vaccination are necessary to elicit particularly strong humoral immune responses, which supports current vaccination recommendations.

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  1. Version published to 10.3390/vaccines10071086
  2. ScreenIT

    SciScore for 10.1101/2022.03.06.22271718: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The study protocol was reviewed and approved by the Ethics Committee of the Medical Council of Hamburg (PV 7298), and written informed consent was obtained by all study participants before recruitment.
    Consent: The study protocol was reviewed and approved by the Ethics Committee of the Medical Council of Hamburg (PV 7298), and written informed consent was obtained by all study participants before recruitment.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    In addition, antibodies against the viral nucleocapsid protein (NC) were detected with the qualitative Elecsys anti-NC-SARS-CoV-2 Ig assay (Roche, Mannheim Germany; cut off ≥ 1 COI/ml), which has a reported sensitivity and specificity of 99.5% and 99.8%, respectively (Roche 2022b).
    anti-NC-SARS-CoV-2
    suggested: None
    Linear regression was calculated among participants with three vaccine doses to predict the anti-S1-RBD-SARS-CoV-2 antibody titer from sex, age, different vaccination regimen, time since the booster vaccination, and presence of anti-NC-SARS-CoV-2 antibodies.
    anti-S1-RBD-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Statistical analyses were performed using GraphPad Prism, version 9 for macOS (GraphPad Software, La Jolla, California, USA) and SPSS, version 26 for macOS (IBM Corporation, Armonk, NY, USA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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 is subject to limitations. We did not recruit a strictly representative sample of hospital employees at our institution, which may limit the generalizability of results. Since employees who have been vaccinated may be more likely to participate in our study, we are not able to reliably assess the COVID-19 vaccination uptake among hospital workers at our institution. Employees with current SARS-CoV-2 infections may not have been able to participate in the current study visit, so we may underestimate the infection rate in our cohort to some degree. While 1253 and 872 hospital workers respectively participated in the last follow-up visits in June 2020 and May 2021, only 697 individuals participated at the current study visit. As in any real-world observational study, the participants were not randomly assigned to different COVID-19 vaccination regimens, and confounding may be expected due to dissimilarities in the different subgroups and differences in the time intervals between the respective vaccine doses and between the last vaccination and the current study visit. Also, given the limited sample size since we subsumed the mRNA vaccines BNT162b2 and mRNA-1273 to one single category and are therefore not able to assess potential differences in immunogenicity amongst different vaccination regimens with one or both of those vaccines. An additional limitation is that we quantitatively assessed the concentration of anti-SARS-CoV-2 antibodies but not their neutralizing cap...

    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.

    About SciScore

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  3. Version published to 10.1101/2022.03.06.22271718 on medRxiv