Long-Term Persistence of IgG Antibodies in recovered COVID-19 individuals at 18 months and the impact of two-dose BNT162b2 (Pfizer-BioNTech) mRNA vaccination on the antibody response

  1. Puya-Dehgani-Mobaraki
  2. Chao Wang
  3. Alessandro Floridi
  4. Emanuela Floridi
  5. Asiya K Zaidi

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Abstract

This era of emerging variants needs a thorough evaluation of data on the long-term efficacy of immune responses in vaccinated as well as recovered individuals, to understand the overall evolution of the pandemic. In this study, we aimed to assess the dynamics of IgG titers over 18 months in n=36 patients from the Umbria region in Italy, who had a documented history of COVID-19 infection in March 2020, and then compared the impact of two-dose BNT162b2 (Pfizer-BioNTech) vaccination on the antibody titers of these patients with the ones who did not receive any dose of vaccine. This is the longest observation (March 2020-September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on the titers. Fixed-effect regression models were used for statistical analysis which could be also used to predict future titer trends. At 18 months, 97% participants tested positive for anti-NCP hinting towards the persistence of infection-induced immunity even for the vaccinated individuals. Our study findings demonstrate that while double dose vaccination boosted the IgG titers in recovered individuals 161 times, this “boost” was relatively short-lived. The unvaccinated recovered individuals, in contrast, continued to show a steady decline but detectable antibody levels. Further studies are required to re-evaluate the timing and dose regimen of vaccines for an adequate immune response in recovered individuals.

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    SciScore for 10.1101/2022.01.18.22269349: (What is this?)

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

    Table 1: Rigor

    EthicsConsent: After detailed written informed consent, serological samples were collected at timed intervals and antibody titers were analyzed using the MAGLUMI® 2019-nCoV lgM/lgG chemiluminescent analytical system (CLIA) assay and the MAGLUMI® SARS-CoV-2 S-RBD IgG CLIA. (New Industries Biomedical Engineering Co.,
    IRB: The blood samples were collected after informed consent by the patients and with the approval of the ethics committee of the Associazione Naso Sano (Document number ANS-2020/001) at an accredited lab (Laboratory of Nuclear Lipid BioPathology, CRABION, Perugia, Italy).
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Patient cohort: A monocentric longitudinal observational study was conducted in patients based in the Umbria region of Italy who had tested positive for SARS-CoV-2 in March 2020 by RT-qPCR, aimed to analyze the presence of antibodies against SARS-CoV-2.
    SARS-CoV-2
    suggested: None

    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:
    [26] Our study had some limitations. First, a small sample size. Second, ideally, simultaneous antibody titer detection of each patient at each time point using both NCP and S-RBD assay would have given the best results for comparative analysis but the S-RBD assay received emergency approval only later in 2020. The nucleocapsid protein (NCP) of the SARS-CoV-2 is considered a biomarker associated with natural exposure. Since this NCP is not present in spike-based vaccines, there is no vaccine-induced response against it in vaccinated individuals. Testing for anti-NCP could be an important tool to analyze the type of existing immunity in an individual (vaccine-induced/ natural/ hybrid). Moreover, Vaccinated individuals who were previously exposed usually test positive for antibodies against NCP (hybrid immunity) while the vaccinated individuals who have never been exposed lack anti-NCP antibodies (vaccine-induced immunity). [27,28] The major strengths of our study include the longest observation (March 2020-September 2021) for the presence of antibodies against SARS-CoV-2 in recovered individuals along with the impact of 2 dose-BNT162b2 vaccination on the titers. Secondly, fixed-effect regression models were used for statistical analysis that diminishes the impact of confounding by (unmeasured) fixed/time-invariant factors. These modeling results could also be used to predict future titer trends. Thirdly, since the immunoassay to detect anti-NCP was reintroduced at 18 months, e...

    Results from TrialIdentifier: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT05038475Enrolling by invitationClinical and Immunological Responses After SARS-CoV-2 Infect…

    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 10.1101/2022.01.18.22269349v1 on medRxiv