Assessing Healthy Vaccinee Effect in COVID-19 Vaccine Effectiveness Studies: A National Cohort Study in Qatar

  1. Hiam Chemaitelly
  2. Houssein H. Ayoub
  3. Peter Coyle
  4. Patrick Tang
  5. Mohammad R. Hasan
  6. Hadi M. Yassine
  7. Asmaa A. Al Thani
  8. Zaina Al-Kanaani
  9. Einas Al-Kuwari
  10. Andrew Jeremijenko
  11. Anvar Hassan Kaleeckal
  12. Ali Nizar Latif
  13. Riyazuddin Mohammad Shaik
  14. Hanan F. Abdul-Rahim
  15. Gheyath K. Nasrallah
  16. Mohamed Ghaith Al-Kuwari
  17. Hamad Eid Al-Romaihi
  18. Mohamed H. Al-Thani
  19. Abdullatif Al-Khal
  20. Roberto Bertollini
  21. Adeel A. Butt
  22. Laith J. Abu-Raddad
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Abstract

Background

This study investigated the presence of the healthy vaccinee effect—the imbalance in health status between vaccinated and unvaccinated individuals—in two COVID-19 vaccine effectiveness studies involving primary series and booster vaccinations. It also examined the temporal patterns and variability of this effect across different subpopulations by analyzing the association between COVID-19 vaccination and non-COVID-19 mortality in Qatar.

Methods

Two matched, retrospective cohort studies assessed the incidence of non-COVID-19 death in national cohorts of individuals with a primary series vaccination versus no vaccination (two-dose analysis), and individuals with three-dose (booster) vaccination versus primary series vaccination (three-dose analysis), from January 5, 2021, to April 9, 2024.

Results

The adjusted hazard ratio (aHR) for non-COVID-19 death was 0.76 (95% CI: 0.64-0.90) in the two-dose analysis and 0.85 (95% CI: 0.67-1.07) in the three-dose analysis. In the first six months of follow-up in the two-dose analysis, the aHR was 0.35 (95% CI: 0.27-0.46); however, the combined analysis of all subsequent periods showed an aHR of 1.52 (95% CI: 1.19-1.94). In the first six months of follow-up in the three-dose analysis, the aHR was 0.31 (95% CI: 0.20-0.50); however, the combined analysis of all subsequent periods showed an aHR of 1.37 (95% CI: 1.02-1.85). The overall effectiveness of the primary series and third-dose vaccinations against severe, critical, or fatal COVID-19 was 95.9% (95% CI: 94.0-97.1) and 34.1% (95% CI: −46.4-76.7), respectively. Subgroup analyses showed that the healthy vaccinee effect is pronounced among those aged 50 years and older and among those more clinically vulnerable to severe COVID-19.

Conclusion

A strong healthy vaccinee effect was observed in the first six months following vaccination. This effect may have stemmed from a lower likelihood of vaccination among seriously ill, end-of-life individuals, and less mobile elderly populations.

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