Open access using this link:

https://onlinelibrary.wiley.com/doi/10.1111/eci.14136

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 0.79.

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, 0.08%.

(IFR, ? 0.008% 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 XBB.1.5. 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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