Effectiveness of the First and Second Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Dose: A Nationwide Cohort Study From Austria on Hybrid Versus Natural Immunity

Alena Chalupka; Uwe Riedmann; Lukas Richter; Ali Chakeri; Ziad El-Khatib; Martin Sprenger; Verena Theiler-Schwetz; Christian Trummer; Peter Willeit; Harald Schennach; Bernhard Benka; Dirk Werber; Tracy Beth Høeg; John P A Ioannidis; Stefan Pilz

doi:10.1093/ofid/ofae547

Effectiveness of the First and Second Severe Acute Respiratory Syndrome Coronavirus 2 Vaccine Dose: A Nationwide Cohort Study From Austria on Hybrid Versus Natural Immunity

Open Forum Infect Dis. 2024 Sep 19;11(10):ofae547. doi: 10.1093/ofid/ofae547. eCollection 2024 Oct.

Authors

Alena Chalupka^{1

2}, Uwe Riedmann¹, Lukas Richter^{2

3}, Ali Chakeri^{2

4}, Ziad El-Khatib², Martin Sprenger⁵, Verena Theiler-Schwetz¹, Christian Trummer¹, Peter Willeit^{6

7

8}, Harald Schennach⁹, Bernhard Benka², Dirk Werber², Tracy Beth Høeg^{10

11}, John P A Ioannidis¹², Stefan Pilz¹

Affiliations

¹ Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
² Institute for Surveillance and Infectious Disease Epidemiology, Austrian Agency for Health and Food Safety, Vienna, Austria.
³ Institute of Statistics, Graz University of Technology, Graz, Austria.
⁴ Centre for Public Health, Medical University Vienna, Vienna, Austria.
⁵ Institute of Social Medicine and Epidemiology, Medical University Graz, Graz, Austria.
⁶ Institute of Clinical Epidemiology, Public Health, Health Economics, Medical Statistics and Informatics, Medical University of Innsbruck, Innsbruck, Austria.
⁷ Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
⁸ Ignaz Semmelweis Institute, Interuniversity Institute for Infection Research, Vienna, Austria.
⁹ Central Institute for Blood Transfusion and Department of Immunology, Tirol Kliniken GmbH, Innsbruck, Austria.
¹⁰ Sloan School of Management, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
¹¹ Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
¹² Departments of Medicine, Epidemiology and Population Health, Biomedical Data Science, and Statistics and Meta-Research Innovation Center at Stanford (METRICS), Stanford University, Stanford, California, USA.

Abstract

Background: We aimed to evaluate the effectiveness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccinations in previously SARS-CoV-2-infected adults in the general population of Austria during the Delta wave and with extended follow-up.

Methods: In a nationwide retrospective cohort study, we calculated age-, sex-, and nursing home residency-adjusted Cox proportional hazard ratios (HRs) of coronavirus disease 2019 (COVID-19) deaths, SARS-CoV-2 infections, and non-COVID-19 deaths from 1 October to 31 December 2021, and secondarily with extended follow-up to 30 June 2022. Relative vaccine effectiveness (rVE) is rVE = (1 - HR) × 100.

Results: Among 494 646 previously infected adults, 169 543 had received 2 vaccine doses, 133 567 had received 1 dose, and 190 275 were unvaccinated at baseline. We recorded 17 COVID-19 deaths (6 vaccinated, 11 unvaccinated) and 8209 SARS-CoV-2 infections. Absolute risk of COVID-19 deaths was 0.003%. rVE estimates for COVID-19 deaths and reinfections exceeded 75% until the end of 2021 but decreased substantially with extended follow-up. The risk of non-COVID-19 death was lower in those vaccinated versus unvaccinated.

Conclusions: First and second SARS-CoV-2 vaccine doses appear effective in the short-term, but with diminishing effectiveness over time. The extremely low COVID-19 mortality, regardless of vaccination, indicates strong protection of previous infection against COVID-19 death. Lower non-COVID-19 mortality in the vaccinated population might suggest a healthy vaccinee bias.

Keywords: COVID-19; SARS-CoV-2; mortality; observational study; vaccine.