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Effectiveness of a fourth SARS-CoV-2 vaccine dose in previously infected individuals from Austria
Evidence is limited on the effectiveness of a fourth vaccine dose against coronavirus disease 2019,
in populations with prior SARS-CoV-2 infections.
We estimated the risk of COVID-19 deaths (primary outcome)
We estimated the risk of SARS-CoV-2 infections (secondary outcome)
Methods
Austria nationwide retrospective observational study.
1 November to 31 December 2022
Primarily comparing individuals with four versus three vaccine doses.
Whole population data.
Results
3,986,312 previously infected individuals
281,291 (7,1%) had four vaccinations at baseline
1,545,242 (38.8%) had three vaccinations at baseline
We recorded
69 COVID-19 deaths
89,056 SARS-CoV-2 infections
The majority of COVID-19 deaths and a significant proportion of all-cause deaths occurred in nursing home residents
Relative vaccine effectiveness (rVE) for four versus three vaccine doses
-24% against COVID-19 deaths
17% against SARS-CoV-2 infections.
Protection against infection rapidly diminished over time,
and infection risk with four vaccinations was higher during extended follow-up until June 2023.
Adjusted HR for all-cause mortality for four versus three vaccinations was .
That is people with a 4th dose were only 79% as likely to die
(Suggesting healthy vaccinee bias, i.e. healthier persons received more vaccine doses)
Discussion
In previously infected individuals, a fourth vaccination did not reduce COVID-19 death risk,
but with transiently reduced risk of SARS-CoV-2 infections,
and reversal of this effect in longer follow-up.
All-cause mortality data suggest healthy vaccinee bias.
More details
Mostly Pfizer vaccine, some Moderna
In this study, overall case fatality rate, %.
(IFR, ? % if 10% of infections picked up)
Individuals with repeated previous infections had reduced re-infection risk
Natural immunity may be a main determinant of immunological protection in a population
By end 2022, the vast majority of the global population had already acquired some immune protection
Compared to three vaccine doses, those with fewer or no vaccinations did not differ with regard to COVID-19 mortality,
but had reduced risk of SARS-CoV-2 infections.
In 2022, infection fatality rates due to SARS-CoV-2 significantly declined suggesting transitioning into endemicity.
In general, our study results question whether recommendations for repeated vaccine boosters against SARS-CoV-2 are currently justified for large parts of the general population with a history of previous infections.
Measures against SARS-CoV-2 including vaccine policy should be critically re-assessed for their risk-to-benefit ratio.
As most SARS-CoV-2 infections are asymptomatic or mild in an endemic phase,
effectiveness of vaccinations should be primarily evaluated according to hard clinical outcomes (e.g. COVID-19 deaths)
Extended follow-up
From 1 January to 30 June 2023
Omicron . was the predominant variant
225 COVID-19 deaths
174,174 SARS-CoV-2 infections.
Analyses in 2023 confirm no relative vaccine effectiveness (rVE) for four versus three vaccine doses for COVID-19 mortality,
but show higher risk of SARS-CoV-2 infections with a rVE of −17%
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