Effectiveness of Primary and Booster COVID-19 mRNA Vaccination against Omicron Variant SARS-CoV-2 Infection in People with a Prior SARS-CoV-2 Infection

  1. Margaret L. Lind
  2. Alexander James Robertson
  3. Julio Silva
  4. Frederick Warner
  5. Andreas C. Coppi
  6. Nathan Price
  7. Chelsea Duckwall
  8. Peri Sosensky
  9. Erendira C. Di Giuseppe
  10. Ryan Borg
  11. Mariam O Fofana
  12. Otavio T. Ranzani
  13. Natalie E. Dean
  14. Jason R. Andrews
  15. Julio Croda
  16. Akiko Iwasaki
  17. Derek A.T. Cummings
  18. Albert I. Ko
  19. Matt DT Hitchings
  20. Wade L. Schulz

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Abstract

Background

The benefit of vaccination in people who experienced a prior SARS-CoV-2 infection remains unclear.

Objective

To estimate the effectiveness of primary (two-dose) and booster (third dose) vaccination against Omicron infection among people with a prior documented infection.

Design

Test-negative case-control study.

Setting

Yale New Haven Health System facilities.

Participants

Vaccine eligible people who received SARS-CoV-2 RT-PCR testing between November 1, 2021, and January 31, 2022.

Measurements

We conducted two analyses, each with an outcome of Omicron BA.1 infection (S-gene target failure defined) and each stratified by prior SARS-CoV-2 infection status. We estimated the effectiveness of primary and booster vaccination. To test whether booster vaccination reduced the risk of infection beyond that of the primary series, we compared the odds among boosted and booster eligible people.

Results

Overall, 10,676 cases and 119,397 controls were included (6.1% and 7.8% occurred following a prior infection, respectively). The effectiveness of primary vaccination 14-149 days after 2 nd dose was 36.1% (CI, 7.1% to 56.1%) for people with and 28.5% (CI, 20.0% to 36.2%) without prior infection. The odds ratio comparing boosted and booster eligible people with prior infection was 0.83 (CI, 0.56 to 1.23), whereas the odds ratio comparing boosted and booster eligible people without prior infection was 0.51 (CI, 0.46 to 0.56).

Limitations

Misclassification, residual confounding, reliance on TaqPath assay analyzed samples.

Conclusion

While primary vaccination provided protection against BA.1 infection among people with and without prior infection, booster vaccination was only associated with additional protection in people without prior infection. These findings support primary vaccination in people regardless of prior infection status but suggest that infection history should be considered when evaluating the need for booster vaccination.

Primary Funding Source

Beatrice Kleinberg Neuwirth and Sendas Family Funds, Merck and Co through their Merck Investigator Studies Program, and the Yale Schools of Public Health and Medicine.

Article activity feed

  1. Version published to 10.1101/2022.04.19.22274056v3 on medRxiv
  2. ScreenIT

    SciScore for 10.1101/2022.04.19.22274056: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: This study was approved by the Yale Institutional Review Board (ID# 2000030222).
    Sex as a biological variablenot detected.
    RandomizationWe chose the TNCC design because it has been shown to provide effectiveness estimates consistent with those from randomized control trials, has been widely applied to estimate real-world effectiveness for COVID-19 vaccines, and mitigates the risk of confounding introduced by care-seeking and testing access.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    No key resources detected.

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:
    Limitations: Our analysis was limited to a population of Connecticut residents and was reliant on medical record data that is subject to misclassification. In the place of whole genome sequence data, we used SGTF status to ascertain Omicron infections as cases. The use of SGTF as a proxy has been widely used during the Omicron epidemic wave and has been recommended as an indicator of Omicron lineage BA.1 infection by the WHO.1,19 While a new sub-lineage of the Omicron variant (BA.2 ) has been detected in the US without SGTF, sequencing data from YNHH showed 100% agreement between SGTF and whole genome sequence-defined Omicron through December 2021.17 In January 2022, we observed a small number (184) of positive tests that did not have SGTF and were not included as cases in the analyses. Our sample is overly representative of mild cases of SARS-CoV-2 infection since TaqPath testing was primarily employed in the YNHH outpatient setting. Additionally, our sample excluded cases with high Ct values since Ct values of at least 30 were required for SGTF calls. We did not have adequate sample to evaluate the level of protection conferred by two or more prior infections (n=49). We expect a proportion of prior SARS-CoV-2 infections may have gone undetected and that ascertainment of prior infection history may be subject to misclassification. Nevertheless, our analyses of people with documented prior infection are unaffected by such misclassification. Despite accounting for health seeki...

    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

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  3. Version published to 10.1101/2022.04.19.22274056v2 on medRxiv
  4. Version published to 10.1101/2022.04.19.22274056v1 on medRxiv