Assessing healthy vaccinee effect in COVID-19 vaccine effectiveness studies: a national cohort study in Qatar
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Abstract
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.
Article activity feed
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Mario Coccia
Review 2: "Assessing Healthy Vaccinee Bias in COVID-19 Vaccine Effectiveness Studies: A National Cohort Study in Qatar"
The overall conclusions that the existence of the healthy vaccinee bias within this cohort is helpful to incorporate when critiquing vaccine effectiveness studies.
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Thiago Cerqueira Silva
Review 1: "Assessing Healthy Vaccinee Bias in COVID-19 Vaccine Effectiveness Studies: A National Cohort Study in Qatar"
The overall conclusions that the existence of the healthy vaccinee bias within this cohort is helpful to incorporate when critiquing vaccine effectiveness studies.
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Strength of evidence
Reviewers: T C Silva (London School of Hygiene and Tropical Medicine) | 📗📗📗📗◻️
M Coccia (National Research Council of Italy) | 📗📗📗📗◻️ -
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