Characterization of the significant decline in humoral immune response six months post‐SARS‐CoV‐2 mRNA vaccination: A systematic review

  1. Kin Israel Notarte
  2. Israel Guerrero‐Arguero
  3. Jacqueline Veronica Velasco
  4. Abbygail Therese Ver
  5. Maria Helena Santos de Oliveira
  6. Jesus Alfonso Catahay
  7. Md. Siddiqur Rahman Khan
  8. Adriel Pastrana
  9. Grzegorz Juszczyk
  10. Jordi B. Torrelles
  11. Giuseppe Lippi
  12. Luis Martinez‐Sobrido
  13. Brandon Michael Henry

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Abstract

Accumulating evidence shows a progressive decline in the efficacy of coronavirus disease 2019 (COVID‐19) (severe acute respiratory syndrome coronavirus 2 [SARS‐CoV‐2]) messenger RNA (mRNA) vaccines such as Pfizer‐BioNTech (mRNA BNT161b2) and Moderna (mRNA‐1273) in preventing breakthrough infections due to diminishing humoral immunity over time. Thus, this review characterizes the kinetics of anti‐SARS‐CoV‐2 antibodies after the second dose of a primary cycle of COVID‐19 mRNA vaccination. A systematic search of the literature was performed and a total of 18 articles ( N  = 15 980 participants) were identified and reviewed. The percent difference of means of reported antibody titers was then calculated to determine the decline in humoral response after the peak levels postvaccination. Findings revealed that the peak humoral response was reached at 21–28 days after the second dose, after which serum levels progressively diminished at 4–6‐month postvaccination. Additionally, results showed that regardless of age, sex, serostatus, and presence of comorbidities, longitudinal data reporting antibody measurement exhibited a decline of both anti‐receptor binding domain immunoglobulin G (IgG) and anti‐spike IgG, ranging from 94% to 95% at 90–180 days and 55%–85% at 140–160 days, respectively, after the peak antibody response. This suggests that the rate of antibody decline may be independent of patient‐related factors and peak antibody titers but mainly a function of time and antibody class/molecular target. Hence, this study highlights the necessity of more efficient vaccination strategies to provide booster administration in attenuating the effects of waning immunity, especially in the appearance of new variants of concerns.

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  1. Version published to 10.1002/jmv.27688
  2. ScreenIT

    SciScore for 10.1101/2021.12.10.21267593: (What is this?)

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

    Table 1: Rigor

    Ethicsnot detected.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power AnalysisIn addition, serial or non-serial serologic measurement determination was done, to differentiate which study performed better patient follow-up, thus reducing methodologic bias due to greater accountability for inter-individual variability despite general lower sample size for serial serologic sampling.

    Table 2: Resources

    Antibodies
    SentencesResources
    For the inclusion criteria, articles reporting the following data were considered: (1) all participants who received a primary vaccination cycle with two complete doses of Pfizer-BioNTech (mRNA BNT162b2) or Moderna (mRNA-1273), (2) with at least a record of 10 patients and above (3) individual IgG or IgA, total Ig, or neutralizing anti-SARS-CoV-2 antibody titers, (4) quantitative or semi-quantitative antibody tests, (6) articles reporting humoral response 4-8– months post-vaccination, (7) articles available in the English language, and (8) randomized controlled, cohort, preprint or published papers and (9) providing complete and extractable data given the limited papers available for this novel disease and the mRNA vaccine.
    mRNA-1273) , ( 2
    suggested: None
    IgA , total Ig ,
    suggested: None
    anti-SARS-CoV-2
    suggested: None
    4%) compared to IgG (93%, 100%, and 98%, respectively).14 IgM antibodies were also found to decline early (i.e., at day 20 post-vaccination) and have lower neutralizing potential.
    IgM
    suggested: None
    Software and Algorithms
    SentencesResources
    As shown in Figure 1, a comprehensive search was carried out in PubMed, Cochrane CENTRAL, Google Scholar, Science Direct, medRxiv, and Research Square for articles published from January 2021 to December 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:
    Regardless of this limitation, when taken together with other studies in this systematic review, those with comorbidities exhibited a similar trend in percent decline with the general population and other cohorts.

    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.

  3. Version published to 10.1101/2021.12.10.21267593v1 on medRxiv