Inpatient Outcomes in a SARS-CoV-2 Naïve Population Achieving High Vaccination Coverage Preceding Planned Virus Entry: A Prospective, Natural Experiment, Pandemic Response Cohort Study.

On November 23, 2021, South Australia lifted border restrictions allowing passive entry of COVID-19 cases into the community. On this date the adult South Australian population was highly vaccinated and COVID-19 naïve (prior infection rate <1:1000). There are no previous outcome data following introduction of SARS-CoV-2 to a susceptible population that was highly vaccinated. The aim of this study was to measure the effect of sole vaccine-derived immunity against SARS-CoV-2, in a virus-naïve population without prior community transmission. This retrospective cohort study of 132,579 adults with COVID-19 was conducted between November 2021 and March 2022. The primary outcome was in-hospital mortality; secondary outcomes were hospital and intensive care unit admission, stratified by vaccination status. Risk-adjusted multivariable logistic regression analysis was performed using a Bayesian framework. Unvaccinated patients had increased odds of death (OR 3.78, 95% credible interval [CrI] 1.20 to 10.58, Bayesian probability of effect [Pr] 0.99), hospital admission (OR 23.9, 95% CrI 19.38 to 29.13, Pr 1.0), and ICU admission (OR 4.68, 95% CrI 1.58 to 12.34, Pr 1.0). Exclusively vaccine-derived immunity against SARS-CoV-2 is unequivocally protective against hospitalization and death. South Australia's pandemic response may be informative in planning for future pandemics, and management of future variants of SARS-CoV-2.