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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.

Published onOct 17, 2024
Review 2: "Assessing Healthy Vaccinee Bias in COVID-19 Vaccine Effectiveness Studies: A National Cohort Study in Qatar"
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Assessing Healthy Vaccinee Effect in COVID-19 Vaccine Effectiveness Studies: A National Cohort Study in Qatar
Assessing Healthy Vaccinee Effect in COVID-19 Vaccine Effectiveness Studies: A National Cohort Study in Qatar
Description

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.

RR\ID Evidence Scale rating by reviewer:

  • Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review: The topics of this paper are interesting, though well known. The structure and content must be revised, and results have to be  better explained by authors to be reconsidered.

Title has to be shorter.

Abstract has to be shorter and clarify the goal, and implications of health policy, based on vaccination,  to face potential pandemics.

Introduction has to better clarify the research questions of this study and provide more theoretical background (this is now poor in its current state) about COVID-19 in the environment and different aspects of COVID-19 vaccines in society. After that, authors can focus on the topics of this study to provide a correct analysis for fruitful discussion.

Methods:

  • Methods of this study is not clear. The section of Materials and Methods must be re-structured with following three sections, because many current sections can be aggregated as follows:

    • Sample and data

    • Measures of variables

    • Models and Data analysis procedure.

  • Study design and the rationale of the methods of inquiry to support results are not clear. Many factors are not controlled, such as the role of variants, mega event in Qatar, climate, seasonality, etc...

  • Authors have to avoid a lot of subheadings that create fragmentation and confusion. If necessary, can use bullet points (same comments for section of results and all sections).

Results:

  • Avoid a lot of sub-headings that create fragmentation of the paper.

  • Results are well known and have to be explained in relation to literature.

  • Tables are too dense of information, difficult to understand. Information can be synthetized and systematized with more figures to be clear for readers. In any case, the paper has a lot of tables that are difficult to digest, some of them can be put in appendix. Inserting the most important/relevant tables into the text will improve the readability.

  • Title of figures must be below the figure and not above, unlike tables, as per scientific writings.

  • Authors have to synthesize the main results in a simple table to be clear for readers and then show what this study adds compared to other studies.

  • Authors have to better describe the results also considering the literature and mega events in Qatar, such as FIFA World  cup, that can affect results.

  • Moreover, a SWOT matrix can systematize the results to support health policy implications based on vaccination to face next pandemics similar to COVID-19.  Explain if these results can be generalized in similar nations.

Conclusion:

  • Conclusion should be able to stand as an autonomous section. Conclusion does not need to be a summary, as authors have to focus on manifold limitations of this study and provide implications of  health and social policy, based on good governance, optimal level of vaccination in population, etc. to improve the roll out of vaccinations to mitigate the effects of new viral agents in society.

Overall comments:

Comments
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