Does the healthy vaccinee bias rule them all? Association of COVID-19 vaccination status and all-cause mortality from an analysis of data from 2.2 million individual health records

Fürst, Tomáš; Bazalová, Angelika; Fryčák, Tadeáš; Janošek, Jaroslav

doi:10.1016/j.ijid.2024.02.019

Cited by 12 publications

(3 citation statements)

References 6 publications

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“…It is crucial to be aware of differences between groups and addressing them in the analysis. Especially if the group comparison considers a vaccinated group versus a non-vaccinated group, it is possible that the data is prone to the healthy vaccine bias, see ( 14 , 15 ). This bias occurs if the vaccinated group is in general more healthy than the comparison group.…”

Section: Discussionmentioning

confidence: 99%

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Protection from prior natural infection vs. vaccination against SARS-CoV-2—a statistical note to avoid biased interpretation

Weber,

Hedberg,

Naucler

et al. 2024

Front. Med.

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IntroductionThe fight against SARS-CoV-2 has been a major task worldwide since it was first identified in December 2019. An imperative preventive measure is the availability of efficacious vaccines while there is also a significant interest in the protective effect of a previous SARS-CoV-2 infection on a subsequent infection (natural protection rate).MethodsIn order to compare protection rates after infection and vaccination, researchers consider different effect measures such as 1 minus hazard ratio, 1 minus odds ratio, or 1 minus risk ratio. These measures differ in a setting with competing risks. Nevertheless, as there is no unique definition, these metrics are frequently used in studies examining protection rate. Comparison of protection rates via vaccination and natural infection poses several challenges. For instance many publications consider the epidemiological definition, that a reinfection after a SARS-CoV-2 infection is only possible after 90 days, whereas there is no such constraint after vaccination. Furthermore, death is more prominent as a competing event during the first 90 days after infection compared to vaccination. In this work we discuss the statistical issues that arise when investigating protection rates comparing vaccination with infection. We explore different aspects of effect measures and provide insights drawn from different analyses, distinguishing between the first and the second 90 days post-infection or vaccination.ResultsIn this study, we have access to real-world data of almost two million people from Stockholm County, Sweden. For the main analysis, data of over 52.000 people is considered. The infected group is younger, includes more men, and is less morbid compared to the vaccinated group. After the first 90 days, these differences increased. Analysis of the second 90 days shows differences between analysis approaches and between age groups. There are age-related differences in mortality. Considering the outcome SARS-CoV-2 infection, the effect of vaccination versus infection varies by age, showing a disadvantage for the vaccinated in the younger population, while no significant difference was found in the elderly.DiscussionTo compare the effects of immunization through infection or vaccination, we emphasize consideration of several investigations. It is crucial to examine two observation periods: The first and second 90-day intervals following infection or vaccination. Additionally, methods to address imbalances are essential and need to be used. This approach supports fair comparisons, allows for more comprehensive conclusions and helps prevent biased interpretations.

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Section: Discussionmentioning

confidence: 99%

“…Frontiers in Medicine 09 frontiersin.org healthy vaccine bias, see (14,15). This bias occurs if the vaccinated group is in general more healthy than the comparison group.…”

Section: Discussionmentioning

confidence: 99%

Protection from prior natural infection vs. vaccination against SARS-CoV-2—a statistical note to avoid biased interpretation

Weber,

Hedberg,

Naucler

et al. 2024

Front. Med.

View full text Add to dashboard Cite

show abstract

“…Frontiers in Medicine 09 frontiersin.org healthy vaccine bias, see (14,15). This bias occurs if the vaccinated group is in general more healthy than the comparison group.…”

Section: Discussionmentioning

confidence: 99%

Data_Sheet_1.pdf

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Does Vaccination Really Mitigate Psychiatric Implications of COVID-19?

Ophir,

Shir-Raz

2024

JAMA Psychiatry

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To the Editor The claim in the study by Walker et al that vaccination may mitigate psychiatric implications of COVID-19 infection 1 comprises 2 subclaims: (1) vaccination protects against COVID-19 infections/severe illness, and (2) COVID-19 infections/severe illness have psychiatric outcomes.The study does not provide support for the first subclaim. Vaccinated individuals had higher rates of infections than unvaccinated, and evidence regarding protection against severe COVID-19 infection is not presented.The study's support to the claim-the indirect association between vaccination and psychiatric outcomes via COVID-19 infections/hospitalizations-requires a comparison with no COVID-19 cases. Evidence that differences between vaccination cohorts existed independently from COVID-19 is implied in the authors' note regarding "…differ-ences… in the absence of COVID-19…." 1(p4) This comparison is required even when confounders are considered, especially when raw hazard ratios (HRs) support the opposite claim. Based on Table 2, we calculated 54.7 depression events per 1000 person-years of vaccinated individuals (vs 46.9 events among those unvaccinated). Moreover, confounders should directly address the well-acknowledged healthy vaccinee bias, which is prevalent in older-age cohorts. 2 After all, the substantial psychiatric risk of the unvaccinated was reported primarily for older adults. For all other age groups, effect sizes were small with some overlapping CIs challenging their significance. In real life, the majority of older adults were vaccinated. 3 The few that were not sometimes belonged to fragile cohorts unable to vaccinate due to immobility or medical ineligibility.The authors' claim that unvaccinated people were less likely to test for COVID-19 infection is doubtful. Real-life vaccine passports required them to get tested often, 4,5 thus inflating their COVID-19 infection rates. The enormous rates of psychiatric outcomes on day 0 augment this selection bias. Unvaccinated individuals seeking psychiatric care might have been required to test for COVID-19 infection, perhaps resulting in COVID-19 and psychiatric diagnoses.

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Does the healthy vaccinee bias rule them all? Association of COVID-19 vaccination status and all-cause mortality from an analysis of data from 2.2 million individual health records

Cited by 12 publications

References 6 publications

Protection from prior natural infection vs. vaccination against SARS-CoV-2—a statistical note to avoid biased interpretation

Protection from prior natural infection vs. vaccination against SARS-CoV-2—a statistical note to avoid biased interpretation

Data_Sheet_1.pdf

Does Vaccination Really Mitigate Psychiatric Implications of COVID-19?

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