SARS-CoV-2 RBD-specific and NP-specific antibody response of healthcare workers in the westernmost Austrian state Vorarlberg: a prospective cohort study

  1. Michele Atzl
  2. Axel Muendlein
  3. Thomas Winder
  4. Peter Fraunberger
  5. Eva-Maria Brandtner
  6. Kathrin Geiger
  7. Miriam Klausberger
  8. Mark Duerkop
  9. Lukas Sprenger
  10. Beatrix Mutschlechner
  11. Andreas Volgger
  12. Magdalena Benda
  13. Luciano Severgnini
  14. Johannes B Jaeger
  15. Heinz Drexel
  16. Alois Lang
  17. Andreas Leiherer

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Abstract

Austria, and particularly its westernmost federal state Vorarlberg, developed an extremely high incidence rate during the COVID-19 pandemic. Healthcare workers (HCWs) worldwide are known to have an increased risk of contracting the disease within the working environment and, therefore, the seroprevalence in this population is of particular interest. We thus aimed to analyse SARS-CoV-2-specific antibody dynamics in Vorarlberg HCWs.

Design

Prospective cohort study of HCWs including testing at three different time points for the prevalence of anti-SARS-CoV-2 IgG antibodies specific for nucleocapsid protein (NP) and receptor-binding domain (RBD).

Setting

All five state hospitals of Vorarlberg.

Participants

A total of 395 HCWs, enrolled in June 2020 (time point 1 (t 1 )), 2 months after the end of the first wave, retested between October and November at the beginning of the second wave (time point 2 (t 2 )) and again at the downturn of the second wave in January 2021 (time point 3 (t 3 )).

Main outcomes

We assessed weak and strong seropositivity and associated factors, including demographic and clinical characteristics, symptoms consistent with COVID-19 infection, infections verified by reverse transcription PCR (RT-PCR) and vaccinations.

Results

At t 1 , 3% of HCWs showed strong IgG-specific responses to either NP or RBD. At t 2 , the rate had increased to 4%, and at t 3 to 14%. A strong response was found to be stable for up to 10 months. Overall, only 55% of seropositive specimen had antibodies against both antigens RBD and NP; 29% had only RBD-specific and 16% only NP-specific antibodies. Compared with the number of infections found by RT-PCR, the number of HCWs being seropositive was 38% higher.

Conclusion and relevance

Serological testing based on only one antigen implicates the risk of missing infections; thus, the set of antigens should be broadened in the future. The seroprevalence among participating HCWs was comparable to the general population in Austria. Nevertheless, in view of undetected infections, monitoring and surveillance should be reconsidered.

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  1. Version published to 10.1136/bmjopen-2021-052130
  2. ScreenIT

    SciScore for 10.1101/2021.02.19.21252045: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementConsent: All participants gave written informed consent and the present study conforms to the ethical guidelines of the 1975 Declaration of Helsinki and has been approved by the Ethics Committee of Vorarlberg (EK-2-4/2020).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    At each time point, venous blood was collected, processed, and anti-SARS-CoV-2 antibodies were detected in human serum via an ELISA specifically detecting IgGs directed against the recombinant NP RBD (5600100 Technozym, Technoclone, Vienna, Austria, (13)) according to the manufacturer’s protocol.
    anti-SARS-CoV-2
    suggested: None
    Software and Algorithms
    SentencesResources
    Study data and laboratory analyses Study data were collected and managed using REDCap electronic data capture tools (16, 17) hosted at VIVIT.
    REDCap
    suggested: (REDCap, RRID:SCR_003445)
    All statistical analyses were performed with SPSS 26.0 for Windows (IBM corp.,
    SPSS
    suggested: (SPSS, RRID:SCR_002865)
    3.5.1 (http://www.r-project.org).
    http://www.r-project.org
    suggested: (R Project for Statistical Computing, RRID:SCR_001905)

    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:
    Further limitations are mentioned in the following. Limitations This study is not a random sample of either the general population or the HCW of Vorarlberg. Included are voluntary and of age HCW. Results are not necessarily applicable to the general population and especially not to children or elderly people (≥ 65 years). At least some results should be interpreted with caution, as it is possible that some of our participants which have been classified to “no response” due to a response below the assay cut-off of <5 U/mL were infected with SARS-CoV-2 a few months before sampling, and either have had only a low antibody response post-infection, and/or have already dropped below the assay threshold. Apart from that, our study only gives information about post-infection antibodyresponse and not about immunity or the chance of reinfections. In that context, it is impossible to fully explain the nature of change of antibody-specific responses in our study, e.g. for responders of which some may be impacted by a secondary contact to the virus thus acting as kind of a booster. Furthermore, it has already been demonstrated that a NP- or spike-specific antibody response may not always be present following a proven SARS-CoV-2 infection (12). Apart from that, a large variety of different commercial ELISAs has been used for the above-mentioned serological study data. Although IgG-specific ELISAs have been proposed to be appropriate for prevalence testing, accuracy significantly differs be...

    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 10.1101/2021.02.19.21252045v2 on medRxiv
  4. Version published to 10.1101/2021.02.19.21252045v1 on medRxiv