• Alena Chalupka, Lukas Richter, Ali Chakeri, Ziad El-Khatib, Verena Theiler-Schwetz, Christian Trummer, Robert Krause, Peter Willeit, Bernhard Benka, IoannidisJohn P AJPA0000-0003-3118-6859Departments of Medicine, Epidemiology and Population Health, Biomedical Data Science, and Statistics and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA., and Stefan Pilz.
• Institute for Surveillance & Infectious Disease Epidemiology, Austrian Agency for Health and Food Safety (AGES), Vienna, Austria.
• Eur. J. Clin. Invest. 2024 Mar 1; 54 (3): e14136e14136.

IntroductionEvidence is limited on the effectiveness of a fourth vaccine dose against coronavirus disease 2019 (COVID-19) in populations with prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. We estimated the risk of COVID-19 deaths and SARS-CoV-2 infections according to vaccination status in previously infected individuals in Austria.MethodsThis is a nationwide retrospective observational study. We calculated age and gender adjusted Cox proportional hazard ratios (HRs) of COVID-19 deaths (primary outcome) and SARS-CoV-2 infections (secondary outcome) from 1 November to 31 December 2022, primarily comparing individuals with four versus three vaccine doses. Relative vaccine effectiveness (rVE) was calculated as (1-HR) X 100.ResultsAmong 3,986,312 previously infected individuals, 281,291 (7,1%) had four and 1,545,242 (38.8%) had three vaccinations at baseline. We recorded 69 COVID-19 deaths and 89,056 SARS-CoV-2 infections. rVE for four versus three vaccine doses was -24% (95% CI: -120 to 30) against COVID-19 deaths, and 17% (95% CI: 14-19) against SARS-CoV-2 infections. This latter effect rapidly diminished over time and infection risk with four vaccinations was higher compared to less vaccinated individuals during extended follow-up until June 2023. Adjusted HR (95% CI) for all-cause mortality for four versus three vaccinations was 0.79 (0.74-0.85).DiscussionIn previously infected individuals, a fourth vaccination was not associated with 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.© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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