Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Naturally Acquired Immunity versus Vaccine-induced Immunity, Reinfections versus Breakthrough Infections: A Retrospective Cohort Study

  1. Sivan Gazit
  2. Roei Shlezinger
  3. Galit Perez
  4. Roni Lotan
  5. Asaf Peretz
  6. Amir Ben-Tov
  7. Esma Herzel
  8. Hillel Alapi
  9. Dani Cohen
  10. Khitam Muhsen
  11. Gabriel Chodick
  12. Tal Patalon

Reviewed by

Read the full article

Discuss this preprint

Start a discussion What are Sciety discussions?

Listed in

Log in to save this article

Abstract

Background

Waning of protection against infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) conferred by 2 doses of the BNT162b2 vaccine begins shortly after inoculation and becomes substantial within 4 months. With that, the impact of prior infection on incident SARS-CoV-2 reinfection is unclear. Therefore, we examined the long-term protection of naturally acquired immunity (protection conferred by previous infection) compared to vaccine-induced immunity.

Methods

A retrospective observational study of 124 500 persons, compared 2 groups: (1) SARS-CoV-2-naive individuals who received a 2-dose regimen of the BioNTech/Pfizer mRNA BNT162b2 vaccine, and (2) previously infected individuals who have not been vaccinated. Two multivariate logistic regression models were applied, evaluating four SARS-CoV-2-related outcomes—infection, symptomatic disease (coronavirus disease 2019 [COVID-19]), hospitalization, and death—between 1 June and 14 August 2021, when the Delta variant was dominant in Israel.

Results

SARS-CoV-2-naive vaccinees had a 13.06-fold (95% confidence interval [CI], 8.08–21.11) increased risk for breakthrough infection with the Delta variant compared to unvaccinated-previously-infected individuals, when the first event (infection or vaccination) occurred during January and February of 2021. The increased risk was significant for symptomatic disease as well. When allowing the infection to occur at any time between March 2020 and February 2021, evidence of waning naturally acquired immunity was demonstrated, although SARS-CoV-2 naive vaccinees still had a 5.96-fold (95% CI: 4.85–7.33) increased risk for breakthrough infection and a 7.13-fold (95% CI: 5.51–9.21) increased risk for symptomatic disease.

Conclusions

Naturally acquired immunity confers stronger protection against infection and symptomatic disease caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 2-dose vaccine-indued immunity.

Article activity feed

  1. Version published to 10.1093/cid/ciac262
  2. ScreenIT

    SciScore for 10.1101/2021.08.24.21262415: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: Ethics declaration: This study was approved by the MHS (Maccabi Healthcare Services) Institutional Review Board (IRB).
    Consent: Due to the retrospective design of the study, informed consent was waived by the IRB, and all identifying details of the participants were removed before computational analysis.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Analyses were performed using Python version 3.73 with the stats model package.
    Python
    suggested: (IPython, RRID:SCR_001658)

    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:
    Our study has several limitations. First, as the Delta variant was the dominant strain in Israel during the outcome period, the decreased long-term protection of the vaccine compared to that afforded by previous infection cannot be ascertained against other strains. Second, our analysis addressed protection afforded solely by the BioNTech/Pfizer mRNA BNT162b2 vaccine, and therefore does not address other vaccines or long-term protection following a third dose, of which the deployment is underway in Israel. Additionally, as this is an observational real-world study, where PCR screening was not performed by protocol, we might be underestimating asymptomatic infections, as these individuals often do not get tested. Lastly, although we controlled for age, sex, and region of residence, our results might be affected by differences between the groups in terms of health behaviors (such as social distancing and mask wearing), a possible confounder that was not assessed. As individuals with chronic illness were primarily vaccinated between December and February, confounding by indication needs to be considered; however, adjusting for obesity, cardiovascular disease, diabetes, hypertension, chronic kidney disease, chronic obstructive pulmonary disease, cancer and immunosuppression had only a small impact on the estimate of effect as compared to the unadjusted OR. Therefore, residual confounding by unmeasured factors is unlikely. This analysis demonstrated that natural immunity affords l...

    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 10.1101/2021.08.24.21262415 on medRxiv