Discussion
infections
REGRESSION, INFECTIONS
Given the substantial immune escape of SARS-CoV-2 variants for the assessment of population immunity, completing S-IgG seroprevalence with serum neutralizing activity is essentialOur results demonstrate a high fraction of participants (95%) with detectable S-IgG but only moderate adherence to current recommendations on COVID-19 vaccinations (67%)Most strikingly, we showed a 23-fold decrease in serum neutralizing activity against BQ.1.1 in comparison to Wu01. This is in line with to-date limited data on BQ.1.1 immune escape and highlights BQ.1.1 as one of the variants with the greatest extent of immune escape that has been observed so farAs shown in our multivariable regression model and Bayesian network analysis, S-IgG levels were predictive for neutralization activity against BQ.1.1. However, we find it important to emphasize that 59.6% of the individuals with detectable S-IgG < 1000 BAU/ml showed no detectable neutralizing activity against BQ.1.1, highlighting the decreased accuracy of S-IgG detection for assessing neutralization in individuals with low S-IgG titers. This information is relevant for clinical routine testing of S-IgG and needs to be considered when assessing COVID-19 risk in patients.To the best of our knowledge, this study is one of the largest that assesses immune evasion of BA.4/5 and BQ.1.1 in a real-life setting. Furthermore, the comprehensiveness of data on medical history, vaccinations, and previous infections of the participants contribute to a reliable assessment of humoral immunity of vulnerable persons before the worldwide predominance of BQ.1.1. However, our study population is not a representative sample of the general population, and by that, the external validity of S-IgG seroprevalence is limited. Nevertheless, we expect that the observed impaired serum neutralization against BQ.1.1 can be generalized as it was controlled for several features including age, pre-conditions, drug immunosuppression, and a number of previous S-antigen contacts. Additionally, this study only analyzes immune evasive properties through neutralization assays. Thus, we cannot determine whether escape is mediated by impaired antibody binding or higher RBD-ACE2 (receptor binding domain-angiotensin-converting enzyme 2) affinityIn summary, we determined a high S-IgG seroprevalence, only moderate compliance with vaccination recommendations, and subsequently a broad range of serum neutralizing activity against BQ.1.1. By that, the observed substantial fraction of persons without detectable neutralizing activity mirrors the consequences of the interplay between immune escape and non-compliance with vaccination recommendations. We conclude that the improvement of vaccine uptake for all eligible individuals is critical for reducing the COVID-19 risk in upcoming waves of BQ.1.1 infections.