tetano
Editor, Senior Moderator
Elife
. 2025 Jun 9:14:e103690.
doi: 10.7554/eLife.103690. Assessing healthy vaccinee effect in COVID-19 vaccine effectiveness studies: a national cohort study in Qatar
Hiam Chemaitelly[SUP] 1 2 3 [/SUP], Houssein H Ayoub[SUP] 4 [/SUP], Peter Coyle[SUP] 5 6 7 [/SUP], Patrick Tang[SUP] 8 [/SUP], Mohammad R Hasan[SUP] 9 [/SUP], Hadi M Yassine[SUP] 5 10 [/SUP], Asmaa A Al Thani[SUP] 5 10 [/SUP], Zaina Al-Kanaani[SUP] 6 [/SUP], Einas Al-Kuwari[SUP] 6 [/SUP], Andrew Jeremijenko[SUP] 6 [/SUP], Anvar Hassan Kaleeckal[SUP] 6 [/SUP], Ali Nizar Latif[SUP] 6 [/SUP], Riyazuddin Mohammad Shaik[SUP] 6 [/SUP], Hanan F Abdul-Rahim[SUP] 11 [/SUP], Gheyath K Nasrallah[SUP] 5 10 [/SUP], Mohamed Ghaith Al-Kuwari[SUP] 12 [/SUP], Hamad Eid Al-Romaihi[SUP] 13 [/SUP], Mohamed H Al-Thani[SUP] 13 [/SUP], Abdullatif Al-Khal[SUP] 6 [/SUP], Roberto Bertollini[SUP] 12 [/SUP], Adeel A Butt[SUP] 3 6 14 [/SUP], Laith J Abu-Raddad[SUP] 2 3 11 15 [/SUP]
Affiliations
Background: This study investigated the presence of the healthy vaccinee effect-the imbalance in health status between vaccinated and unvaccinated individuals-in two rigorously conducted 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 6 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 6 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.
Conclusions: A pronounced healthy vaccinee effect was observed during the first 6 months following vaccination, despite meticulous cohort matching. This effect may have stemmed from a lower likelihood of vaccination among seriously ill, end-of-life individuals, and less mobile elderly populations.
Funding: Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, and Junior Faculty Transition to Independence Program, all at Weill Cornell Medicine-Qatar, Qatar University, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and L'Oréal-UNESCO For Women In Science Middle East Regional Young Talents Program.
Keywords: COVID-19; all-cause mortality; bias; cohort study; epidemiology; global health; vaccine; viruses.
. 2025 Jun 9:14:e103690.
doi: 10.7554/eLife.103690. Assessing healthy vaccinee effect in COVID-19 vaccine effectiveness studies: a national cohort study in Qatar
Hiam Chemaitelly[SUP] 1 2 3 [/SUP], Houssein H Ayoub[SUP] 4 [/SUP], Peter Coyle[SUP] 5 6 7 [/SUP], Patrick Tang[SUP] 8 [/SUP], Mohammad R Hasan[SUP] 9 [/SUP], Hadi M Yassine[SUP] 5 10 [/SUP], Asmaa A Al Thani[SUP] 5 10 [/SUP], Zaina Al-Kanaani[SUP] 6 [/SUP], Einas Al-Kuwari[SUP] 6 [/SUP], Andrew Jeremijenko[SUP] 6 [/SUP], Anvar Hassan Kaleeckal[SUP] 6 [/SUP], Ali Nizar Latif[SUP] 6 [/SUP], Riyazuddin Mohammad Shaik[SUP] 6 [/SUP], Hanan F Abdul-Rahim[SUP] 11 [/SUP], Gheyath K Nasrallah[SUP] 5 10 [/SUP], Mohamed Ghaith Al-Kuwari[SUP] 12 [/SUP], Hamad Eid Al-Romaihi[SUP] 13 [/SUP], Mohamed H Al-Thani[SUP] 13 [/SUP], Abdullatif Al-Khal[SUP] 6 [/SUP], Roberto Bertollini[SUP] 12 [/SUP], Adeel A Butt[SUP] 3 6 14 [/SUP], Laith J Abu-Raddad[SUP] 2 3 11 15 [/SUP]
Affiliations
- PMID: 40488740
- DOI: 10.7554/eLife.103690
Background: This study investigated the presence of the healthy vaccinee effect-the imbalance in health status between vaccinated and unvaccinated individuals-in two rigorously conducted 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 6 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 6 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.
Conclusions: A pronounced healthy vaccinee effect was observed during the first 6 months following vaccination, despite meticulous cohort matching. This effect may have stemmed from a lower likelihood of vaccination among seriously ill, end-of-life individuals, and less mobile elderly populations.
Funding: Biomedical Research Program and the Biostatistics, Epidemiology, and Biomathematics Research Core, and Junior Faculty Transition to Independence Program, all at Weill Cornell Medicine-Qatar, Qatar University, Ministry of Public Health, Hamad Medical Corporation, Sidra Medicine, Qatar Genome Programme, Qatar University Biomedical Research Center, and L'Oréal-UNESCO For Women In Science Middle East Regional Young Talents Program.
Keywords: COVID-19; all-cause mortality; bias; cohort study; epidemiology; global health; vaccine; viruses.