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.

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