Effects of Age, Sex, Serostatus and Underlying Comorbidities on Humoral Response Post-SARS-CoV-2 Pfizer-BioNTech Vaccination – A Systematic Review

  1. Kin Israel Notarte
  2. Abbygail Therese Ver
  3. Jacqueline Veronica Velasco
  4. Adriel Pastrana
  5. Jesus Alfonso Catahay
  6. Gian Luca Salvagno
  7. Eric Peng Huat Yap
  8. Luis Martinez-Sobrido
  9. Jordi Torrelles
  10. Giuseppe Lippi
  11. Brandon Michael Henry

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Abstract

With the advent of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic, several vaccines have been developed to mitigate its spread and prevent adverse consequences of the Coronavirus Disease 2019 (COVID-19). The mRNA technology is an unprecedented vaccine, usually given in two doses to prevent SARS-CoV-2 infections. Despite effectiveness and safety, inter-individual immune response heterogeneity has been observed in recipients of mRNA-based vaccines. As a novel disease, the specific immune response mechanism responsible for warding off COVID-19 remains unclear at this point. However, significant evidence suggests that humoral response plays a crucial role in affording immunoprotection and preventing debilitating sequelae from COVID-19. As such this paper focused on the possible effects of age, sex, serostatus, and comorbidities on humoral response ( i . e ., total antibodies, IgG and/or IgA) of different populations post-mRNA-based Pfizer-BioNTech vaccination. A systematic search of literature was performed through PubMed, Cochrane CENTRAL, and Google Scholar. Studies were included if they reported humoral response to COVID-19 mRNA vaccines. A total of 32 studies was identified and reviewed, and the percent difference of means of reported antibody levels were calculated for comparison. Findings revealed that older individuals, the male sex, seronegativity, and those with more comorbidities mounted less humoral immune response. Given these findings, several recommendations were proposed regarding the current vaccination practices. These include giving additional doses of vaccination for immunocompromised and elderly populations. Another recommendation is conducting clinical trials in giving a combined scheme of mRNA vaccines, protein vaccines, and vector-based vaccines.

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  1. ScreenIT

    SciScore for 10.1101/2021.10.10.21264825: (What is this?)

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

    Table 1: Rigor

    EthicsField Sample Permit: Search Strategy and Eligibility Criteria: A systematic literature search was conducted to identify studies reporting the factors affecting humoral response of individuals who received the mRNA vaccines.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For the inclusion criteria, articles reporting the following data were considered: (1) total IgG or IgA or neutralizing antibody titers, (2) quantitative antibody tests, (3) mRNA-based vaccines, (4) articles reporting time points for data extraction, (5) articles available in the English language, and (6) randomized controlled, cohort, preprint or published papers as long as they provide extractable data given the limited papers available for this novel disease and the mRNA vaccine.
    total IgG
    suggested: None
    IgA
    suggested: None
    Software and Algorithms
    SentencesResources
    As shown in Figure 1, a comprehensive search was carried out in PubMed, Cochrane CENTRAL, and Google Scholar for articles published from January to end of July 2021.
    PubMed
    suggested: (PubMed, RRID:SCR_004846)
    Cochrane CENTRAL
    suggested: (Cochrane Central Register of Controlled Trials, RRID:SCR_006576)
    Google Scholar
    suggested: (Google Scholar, RRID:SCR_008878)

    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:
    It also highlights the need to individualize vaccination programs and create strategies to account for possible age-related limitations for COVID-19 vaccination [14]. Sex: Females develop a greater antibody response due to hormonal differences compared to males, which regulates both adaptive and innate immune responses, with estradiol and testosterone having enhancing and suppressive effects, respectively [19]. However, levels of sex hormones change with age. Thus, after menopause the drop in estradiol levels enhances immunosenescence [19]. Studies in childhood vaccination enables research that focus on sex-dependent response aside from sex hormones that increase after puberty. Such is the case in studies on Measles, Mumps, and Rubella (MMR) and Diphtheria, Pertussis, and Tetanus (DPT) vaccines [20]. These suggest that genetic factors may play a role. The X chromosome expresses more genes, many of which influence immunity. This includes microRNAs (miRNAs) that are known to modulate immunity [20]. Several studies suggest that a similar trend is also observed among COVID-19 mRNA vaccines, noting a higher humoral response and adverse events among women. Among the articles reviewed in Table 2, two studies showed a direct relationship between sex and humoral response. Both studies by Jabal et al. and Pellini et al. reported that the female sex is generally superior to male in terms of production of IgG in Day 21 and Day 28 post-vaccination of Pfizer-BioNtech, respectively [13,16]....

    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

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.10.10.21264825v1 on medRxiv