SARS-CoV-2 infection in fully vaccinated individuals of old age strongly boosters the humoral immune response

  1. Lisa Müller
  2. Marcel Andrée
  3. Philipp Niklas Ostermann
  4. Nathalie Jazmati
  5. Greta Flüh
  6. Johannes Fischer
  7. Edwin Bölke
  8. Hilmar Wisplinghoff
  9. Heiner Schaal
  10. Ingo Drexler
  11. Andreas Walker
  12. Ortwin Adams
  13. Jörg Timm

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Abstract

Introduction

Prophylactic vaccination against SARS-CoV-2 is one of the most important measures to contain the COVID-19 pandemic. Recently, break-through infections following vaccination against this virus have been reported. Here, we describe the humoral immune response of break-through infections in fully vaccinated individuals of old age from an outbreak in a nursery home.

Methods

In cooperation with the local health authority, blood samples from fully vaccinated and infected as well as fully vaccinated and uninfected residents of the nursery home were collected four weeks after the onset of the outbreak. The humoral immune response was determined in a neutralisation assay with replication-competent virus isolates and by a quantitative ELISA.

Results

In this outbreak a total of 23 residents and four health care workers were tested positive for SARS-CoV-2. Four residents were unvaccinated, including one with a severe course of disease who later deceased. Despite their old age, all vaccinated residents showed no or only mild disease. Comparison of the humoral immune response revealed significantly higher antibody levels in fully vaccinated infected individuals compared to fully vaccinated uninfected individuals (p<0.001). Notably, although only a minority of the vaccinated uninfected group showed neutralisation capacity against SARS-CoV-2, all vaccinated and infected individuals showed high-titer neutralisation of SARS-CoV-2 including the alpha and beta variant.

Discussion

Large SARS-CoV-2 outbreaks can occur in fully vaccinated populations, but seem to associate with mild disease. SARS-CoV-2 infection in fully vaccinated individuals is a strong booster of the humoral immune response providing enhanced neutralisation capacity against immune evasion variants.

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  1. ScreenIT

    SciScore for 10.1101/2021.07.19.21260563: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: The retrospective analysis of the outbreak was approved by the ethics committee of the Medical Faculty of the Heinrich-Heine University Duesseldorf, (study no. 2021-1481).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Detection of SARS-CoV-2-specific antibodies: Samples were tested for anti-SARS-CoV-2 antibodies using two commercially available test systems.
    anti-SARS-CoV-2
    suggested: None
    It detects SARS-CoV-2 nucleocapsid-specific (N) IgG antibodies.
    IgG
    suggested: None
    SARS-CoV-2 spike specific IgG antibodies, induced by either vaccination or infection were measured using the Euroimmun SARS-CoV-2-QuantiVac-ELISA on the Euroimmun Analyzer I-2P according to the manufacturer’s instructions.
    SARS-CoV-2 spike specific IgG
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    After pre-incubation, 100µl of cell suspension containing 7×104/ml Vero cells (ATTC-CCL-81) were added.
    Vero
    suggested: None
    Software and Algorithms
    SentencesResources
    When possible, whole-genome sequencing (WGS) of SARS-CoV-2 was performed by the diagnostic laboratory where the initial PCR testing was performed.
    WGS
    suggested: None
    To distinguish antibody responses induced by vaccination from those induced by SARS-CoV-2 infections, the SARS-CoV-2 IgG chemiluminescent microparticle immunoassay (CMIA) from Abbott was performed on an ARCHITECT i2000Abbott.
    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: We detected the following sentences addressing limitations in the study:
    The lack of longitudinal data as well as a control group of persons without vaccination examined in the same period after infection are important limitations of this study. It is noteworthy that the neutralisation titres were on average significantly lower in unvaccinated convalescents analysed at our lab with the same assay compared to vaccinated and infected individuals (data not shown). Even after complete vaccination, neutralising antibodies are not detectable in all individuals. Especially in elderly and immunosuppressed people, immunity after vaccination is less pronounced. In a previous study, about 30% of those over 80 years of age had no neutralising activity against the prototype virus three weeks after the second dose of an mRNA vaccine (Müller, Andrée et al. 2021). In this study, the antibody response was at the same low level in vaccinated individuals at comparable ages about eight weeks after vaccination. Infection after vaccination, as in this case with the alpha variant of SARS-CoV-2, thus appears to strongly boost immunity. It should be emphasised that vaccinated individuals showed considerable cross-reactivity after infection, which also neutralises the beta variant. The functional immune escape of the beta variant is particularly evident in the loss of neutralisation activity at low antibody levels. It is therefore reasonable to assume that boosting of immunity by an infection may provide additional protection against variants. Although it seems possible 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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  2. Version published to 10.1101/2021.07.19.21260563v1 on medRxiv