Monitoring of anti-SARS-CoV-2 IgG antibody immune response in infected and immunised healthcare workers in Hungary: a real-world longitudinal cohort study

  1. Judit Gervain
  2. Katalin B. Szabó
  3. Erika H. Baki
  4. Lídia Kadlecsik
  5. Attila Gyenesei
  6. Róbert Herczeg
  7. Judit Simon

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Abstract

Introduction

SARS-CoV-2 infections have very different clinical manifestations and anti-SARS-CoV-2 immunisation may also trigger very different levels and length of protection. While (re)infection after previous COVID-19 illness or following vaccination are known, their impact and the optimal timing of any booster vaccination is currently debated. International evidence about potential underlying immune response differences remains limited and is currently not available in Hungary.

Methods

We prospectively investigated the magnitude of immune responses to infection or immunisation, their over-time changes and the occurrence of new infections through anti-SARS-CoV-2 IgG levels and the association with selected individual and clinical parameters in two voluntary cohorts of healthcare workers at a public teaching hospital in a real-world longitudinal cohort study in Hungary. In the first cohort, the anti-nucleocapsid IgG levels of 42 health care workers (female: 100%) with SARS-CoV-2 infection were followed-up over 8 months between June 2020 and February 2021. Beyond the change in immune response, associations with age, selected existing chronic conditions, blood type and severity of symptoms were investigated. In the immunised cohort, anti-spike-RBD protein IgG levels of 49 health care workers (female: 73%) with no prior COVID-19 infection were monitored up to 4 months following initial immunisation with BNT162b2 vaccine between December 2020 and April 2021. Statistical analyses included median analysis, linear regression, ANCOVA, Kruskal-Wallis test and Skillings-Mack test for block designs as relevant.

Results

Within the infected cohort, the median time of anti-SARS-CoV-2 IgG level reduction below the positive test cut-off was 6 months. First month IgG levels were on average the highest among those in illness severity category 4, but the difference to less severe categories was not statistically significant. Higher age was associated with higher IgG levels. Within the immunised cohort, the anti-SARS-CoV-2 spike-RBD protein IgG levels increased 25-fold between the first and second immunisations, significantly decreased to 33% of the peak level after 90 days, and had an overall negative tendency with older age and male sex. IgG monitoring revealed 17% (7/42) and 14% (7/49) new infections in the infected and the immunised cohorts, respectively, all symptomless.

Discussion

Our study is the first to investigate the level, change and associations of anti-SARS-CoV-2 IgG immune response in infected or immunised healthcare workers in Hungary. It provides further evidence about the significantly declining IgG protection through initial infection beyond 6 months. While immunisation with mRNA vaccination shows a similar pattern of reduction in protection, IgG levels remained within the positive range at 4 months. The observed rate of 15% new, asymptomatic infections and their potential broader impacts call for further investigations. Overall, our findings are confirmative of the effectiveness of vaccination to prevent illness, recent considerations for booster vaccination beyond 6 months, and indicate the potential benefit of anti-SARS-CoV-2 IgG monitoring for optimisation.

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  1. ScreenIT

    SciScore for 10.1101/2021.05.16.21257288: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Participants had to be over 18 years, employed by the hospital, currently not on high-dose immune suppressive therapy, and willing and able to give written consent to participate in the study.
    IRB: The study was approved by the Local Institutional Committee of Science and Research Ethics (Nr. 16/20200723).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Positive diagnostic levels were defined as >1.4 s/c. [4, 6, 18] For cohort 2, anti-SARS-CoV-2 spike-RBD levels were measured with chemiluminescent microparticle immunoassay method (CMIA) using the quantitative SARS-CoV-2 IgG II Quant Assay (Abbott) and Architect i2000SR immunoassay analyser (Abbott).
    Abbott
    suggested: (Abbott, RRID:SCR_010477)

    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.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

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  2. Version published to 10.1101/2021.05.16.21257288v1 on medRxiv