Determining SARS-CoV-2 immunity is critical to assess COVID-19 risk and the need for prevention and mitigation strategies. We measured SARS-CoV-2 Spike/Nucleocapsid seroprevalence and serum neutralizing activity against Wu01, BA.4/5 and BQ.1.1 in 1,411 individuals who received medical treatment in five emergency departments in North Rhine-Westphalia, Germany. We detected Spike-IgG in 95.6%, Nucleocapsid-IgG in 24.0% and neutralization against Wu01, BA.4/5 and BQ.1.1 in 94.4%, 85.0%, and 73.8% of participants, respectively. Neutralization against BA.4/5 and BQ.1.1 was reduced 5.6- and 23.4-fold compared to Wu01. Accuracy of S-IgG detection for determination of neutralizing activity against BQ.1.1 was reduced substantially. Furthermore, we explored previous vaccinations and infections as most important correlates of improved BQ.1.1 neutralization using multivariable and Bayesian network analyses. Given an adherence to COVID-19 vaccination recommendations of only 67.7% of all participants, we highlight the need for improvement of vaccine-uptake to reduce the COVID-19 risk in upcoming infection-waves with immune evasive variants.
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