Analysis of Immunization, Adverse Events, and Efficacy of a Fourth Dose of BNT162b2 Vaccine in Health Workers in Mexico, a Pilot Study

  1. Maria Elena Romero-Ibarguengoitia
  2. Arnulfo González-Cantú
  3. Diego Rivera-Salinas
  4. Yodira Guadalupe Hernández-Ruíz
  5. Ana Gabriela Armendariz-Vázquez
  6. Irene Antonieta Barco-Flores
  7. Rosalinda González-Facio
  8. Miguel Ángel Sanz-Sánchez

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Abstract

There is scarce information on seroconversion and adverse events after immunization (AEFI) with the fourth dose of BNT162b2. Our aim was to correlate the magnitude of the antibody response to this vaccination regimen in terms of clinical conditions and AEFI. This was an observational pilot study in which SARS-CoV-2 S1–S2 IgG antibodies titers were measured 21–28 days after the first and second dose, three months after the second dose, 1–7 and 21–28 days after the third dose, before the fourth dose, and 21–28 days after the fourth dose. We recruited 112 subjects in a hospital in Mexico, 74% women, with an average age of 43 (SD 9) years. After the first dose, subjects had a median IgG AU/mL (IQR) of 122 (1904) that increased to 1875 (2095), 3020 (2330), and 4230 (3393) 21–28 days after the second, third, and fourth doses, respectively (p < 0.01). The number (%) who experienced any AEFI between the first and fourth doses was 90 (80.4), 89 (79), 65 (58), and 69 (61.5), respectively (p < 0.001). After the fourth dose, the most frequent of AEFI was pain at the injection site (87%). There was a correlation between AEFI and gender after the fourth dose, as well as with antibody levels (p < 0.05). During the Omicron outbreak, six (5.3%) had mild COVID-19 for 8–28 days after the fourth dose. The median increase in S1/S2 IgG was 30.8-fold after the fourth BNT162b2 dose when compared with the first dose and caused mild AEFI.

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  1. Version published to 10.3390/vaccines10071139
  2. ScreenIT

    SciScore for 10.1101/2022.04.05.22273434: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: 12 Our study received approval from the local Institutional Review Board /Ref.;26022021-CN-1e-CI) and was conducted per the Code of Ethics of the World Medical Association (Declaration of Helsinki) for experiments that involve humans.
    Consent: Every participant signed an informed consent where the study was explained.
    Sex as a biological variableThe inclusion criteria were healthcare professionals of both genders and any age who consented to participate, with a complete BNT162b2 national vaccination regimen, the application of the third BNT162b2 dose 4-6 months after the original vaccination scheme, and an additional BNT162b2 booster 4-6 months following the third dose.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Specific anti S1-S2 IgG antibodies against SARS-CoV-2 were measured by laboratory personnel using a chemiluminescence immunoassay (CLIA) by DiaSorin.
    anti S1-S2 IgG
    suggested: None
    SARS-CoV-2
    suggested: None
    We performed a Friedman test to compare the anti S1 and S2 antibody titers through time and a Mann Whitney U test to compare antibody levels between subjects previously exposed to SARS-CoV-2.
    anti S1
    suggested: None
    S2
    suggested: None
    We performed an individual variation as a random effect, and the fixed effects were the time of every anti S1-S2 antibody, gender, and age.
    anti S1-S2
    suggested: None
    Software and Algorithms
    SentencesResources
    SPSS version 25 and R v 4.0.4 was the statistical program used to analyze data.
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:
    As for limitations of our study, this is an observational study, so we lack randomization and a control group; however, we were able to compare our information with previously published data. A larger sample size would be of interest for testing for other predictors of antibody change; however, the changes of antibody titers between doses were so different that we could achieve enough statistical power for the inferences addressed in the present manuscript. This study did not include basal antibody measurement because, unfortunately, we could not obtain these samples since our protocol was accepted after all participants had received the first dose. However, we think this manuscript is valuable since new SARS-COV2 variants are emerging, and scarce information exists concerning a fourth dose that could help prevent infection or severe cases. Future studies about new generation vaccines against SARS-CoV-2 are required to compare the results with this regimen. In conclusion, the fourth dose of BNT162b2mRNA produced a humoral response by increasing 33.6 times S1/S2 IgG compared to one dose, with mild adverse events. Women had more AEFI after the fourth dose, and there is a small effect related to the antibody level. Even though the Omicron variant is contagious, we found a similar infection rate to the Delta variant after subjects received the fourth dose. All the infected cases were mild and treated ambulatory.

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

    IdentifierStatusTitle
    NCT05228912RecruitingImmunization of 7 Different Vaccines Against SARS-COV-2 Acro…

    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.
    • Thank you for including a protocol registration statement.

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

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  3. Version published to 10.1101/2022.04.05.22273434 on medRxiv