Austrian national registry data covering the whole adult population with no documented prior SARS-CoV-2 infection were used to compare mortality between vaccinated and unvaccinated people, adjusting for age, sex, long-term care allowance and education. Vaccinated individuals had lower all-cause mortality irrespective of dose number, with adjusted hazard ratios of 0.38 to 0.52 in the quarter after each vaccination was introduced and 0.24 to 0.32 in the two weeks after a dose in the matched analysis. Cancer mortality and deaths from external causes followed the same pattern, causes that vaccination cannot plausibly influence.
Why it is interesting: It puts a national-scale figure on the selection bias that inflates observational estimates of COVID-19 vaccine effectiveness, and shows it is largest in exactly the window such studies use.
Abstract — the authors' own words, CC BY
ABSTRACT
Importance
Estimates of SARS-CoV-2 vaccine effectiveness (VE) from observational studies may be biased if healthier (healthy vaccinee effect; HVE) or less healthy individuals are preferentially vaccinated. Quantifying HVE is essential for interpreting VE estimates for informed vaccination policy. Objective
To assess the HVE by comparing all-cause mortality, cancer mortality, and deaths from external causes between vaccinated and unvaccinated individuals. Design, Setting, and Participants
This nationwide retrospective cohort study used Austrian national registry data from 2021 to August 31, 2022, and included the entire adult population of Austria with no previously documented SARS-CoV-2 infection on January 1, 2021. Cox regression was used to estimate hazard ratios (HRs) for mortality comparing vaccinated with unvaccinated individuals while adjusting for age, sex and Austrian long-term care allowance (ALTCA) recipiency, stratified by vaccinations (1 to 4). Analyses were performed for the whole observation period, 3-month blocks (quarters) and the 2 months with highest and lowest COVID-19 disease burden per year. Additionally, newly vaccinated individuals were matched on day of vaccination based on the aforementioned covariates plus highest education and HRs were assed for the two weeks following vaccination. Exposure
Receipt of at least 1 dose of SARS-CoV-2 vaccine. Main Outcomes and Measures
All-cause mortality, cancer mortality, and deaths from external causes (e.g., falls and transport accidents). Results
Among 7,416,077 eligible adults, all-cause mortality was lower among vaccinated than unvaccinated individuals regardless of vaccination number. Differences in risk were greatest shortly after vaccination and attenuated over time. E.g., adjusted all-cause HRs in the quarter after vaccination introduction were 0.46, 0.52, 0.38 and 0.43 for vaccinated vs unvaccinated individuals for 1, 2, 3 and 4 vaccinations, respectively. Respective HRs for the first 2 weeks after vaccination in the matched analysis were 0.24-0.32 across all vaccinations. Findings for cancer mortality and deaths from external causes paralleled those for all-cause mortality. Conclusions and Relevance
A pronounced HVE was observed for SARS-CoV-2 vaccination during the pandemic, evidenced by markedly lower mortality from causes not plausibly related to vaccination (cancer, external causes) among vaccinated individuals. This bias needs to be accounted for when interpreting observational estimates of SARS-CoV-2 VE.
Cite this item
BibTeX
Free sign-up. A digest of the new papers twice a week, grouped by domain.
Other drivers in Data, models and systems
-
Forecasts and their record
How the forecasts are made, how well they explained the past, and how well mortality can be forecast — and by whom.
7 this week -
What linked data reveals
What linked registries make it possible to know about whole populations
9 this week -
AI in medicine
Whether machine learning predicts, detects and decides better than the tools we have, and whether that has yet changed an outcome for a population.
3 this week -
Health systems and access
What the health system can provide, who gets it, and whether the gaps in health between groups are widening.
6 this week -
Value in health
What a treatment, health programme or policy is worth against what it costs, and how far the models that decide it can be trusted.
6 this week -
Revisions and new sources
What the figures are built from, what is newly available, and how much the numbers move when they are revised.
7 this week
