Immune responses after twofold SARS-CoV-2 immunisation in elderly residents and Health Care Workers in nursing homes and homes with assisted living support - Proposal for a correlate of protection

  1. Julia Schiffner
  2. Nora Eisemann
  3. Hannah Baltus
  4. Sina Jensen
  5. Katharina Wunderlich
  6. Stefan Schüßeler
  7. Charlotte Eicker
  8. Bianca Teegen
  9. Doreen Boniakowsky
  10. Werner Solbach
  11. Alexander Mischnik

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Abstract

In the present study, we were interested in the decline over time of anti SARS-CoV-2 antibodies and SARS-CoV-2 specific T-cell responses after two doses of mRNA vaccines in total and by age group and comorbidity. The second goal was to suggest an immunological correlate for protection on an individual basis and to describe the probability of protection over time after second vaccination.

We analysed blood samples from 228 residents (median age 83.8 years) and from 273 Health Care Workers (HCW; median age 49.7 years) of five nursing homes and one home for the elderly with assisted living support. Participants had received two vaccinations. The blood samples were analysed for SARS-CoV-2 specific antibody and T-cell responses. We compared outcomes in the HCW and residents in the respective institutions. No breakthrough infections occurred during the study period. The initial immune responses in the younger participants were about 30 % higher than in the older ones. Over time, all parameters dropped continuously in all groups within the maximum observation period of 232 days. Comorbidities such as coronary heart disease or diabetes mellitus reduced the initial immune responses, regardless of age. In contrast to an almost linear decline in antibody levels, we observed that the interferon-gamma response remained at a constant level between about day 120 and 180, only to decline further thereafter.

Based on our data, we propose on an individual level a correlate of protection: Persons who have a neutralizing capacity of 75 % (which would correspond to approx. 200 BAU/ml) and an interferon-gamma response above 200 mIU/ml should be considered to be protected resp. sufficiently immunized.

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  1. ScreenIT

    SciScore for 10.1101/2022.02.09.22270747: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: Inclusion criteria were being vaccinated twice against SARS-CoV-2, an elapsed period of at least 14 days since the second vaccination (as the vaccination effect is first built up during this time) and written informed consent.
    IRB: Ethics: The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (10) and approved by the ethics committee of the University of Luebeck (21-353).
    Sex as a biological variableSubgroup analyses by age (age below 65 years versus 65+), sex (female versus male) and comorbidity (no versus any comorbidity) were done.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Exclusion criteria were a third vaccination, unknown date of second vaccination, unsuccessful blood drawings, no laboratory result of the blood sample or a positive test for anti-SARS-CoV-2 nucleocapsid protein (NCP) antibodies.
    anti-SARS-CoV-2 nucleocapsid protein (NCP)
    suggested: None
    Laboratory methods: The blood samples were analysed for four main outcomes: anti-SARS-CoV-2 S1-Protein IgG antibodies, antibody neutralization capacity, SARS-CoV-2 S1 reactive T cells (i. e. interferon-gamma release assay, IGRA) and anti-SARS-CoV-2 nucleocapsid protein antibodies.
    anti-SARS-CoV-2 nucleocapsid protein
    suggested: None
    The measured “relative units/ml” were calibrated with the “First WHO standard of anti-SARS-CoV-2 immunoglobulin” (NIBSC code 20/136) and converted into Binding Antibody Units (BAU)/ml by multiplication with the factor 3.2.
    anti-SARS-CoV-2
    suggested: None
    Pairwise correlation coefficients were calculated for SARS-CoV-2 S1 reactive T cells, anti-SARS-CoV-2 S1-Protein IgG antibodies and antibody neutralization capacity.
    anti-SARS-CoV-2 S1-Protein IgG
    suggested: None
    A log-linear regression model predicted that an antibody neutralization capacity value of 75 % corresponds to an IgG antibody value of about 200 BAU/ml.
    an IgG
    suggested: (Hangzhou HuaAn Biotechnology Cat# HA1001, RRID:AB_2819166)

    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:
    We are very aware that immunological tests are subject to a number of limitations. Although manifold evidence suggests that there is a correlation between neutralising activity in plasma and protection from symptomatic infection at the population level, the titres of neutralising antibodies decrease over time after infection or vaccination; the kinetics of the decrease vary from person to person. Even normalisation to the WHO standard may not fully compensate for the inter-assay variability of pseudovirus-based neutralisation assays. High speed development of variants (of concern) with presumably altered surface properties makes prognosis of protection somewhat difficult, e.g. shift from delta to omicron basically led to a shift from protection against infection” to (limited) protection against severe sequelae/ severe disease”. Consequently this protection correlate might (as an absolute value) only hold true for conditions present during the study period. Furthermore, exposure to high viral loads would require higher protective titres than exposure to low viral loads (e.g. when masks are worn). Conclusions: Our study makes statements from a time when the Delta variant was predominant. The conclusions do not necessarily apply to other variants such as Omikron. For residents, the mean time between the second vaccination and blood collection was 22 days longer than for HCW (195 days and 173 days, respectively). This could influence the results in such a way that the decline of ...

    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 10.1101/2022.02.09.22270747 on medRxiv