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Serological assays can detect anti-SARS-CoV-2 antibodies, but their sensitivity often comes at the expense of specificity. Here we developed a Tripartite Automated Blood Immunoassay (TRABI) to assess the IgG response against SARS-CoV-2. Calibration was performed with 90 prepandemic and 55 virologically and clinically confirmed COVID-19 samples. Posterior probabilities were calculated from 3×8 measurements of logarithmically diluted samples against the ectodomain and the receptor-binding domain of the spike protein and the nucleocapsid protein. We then performed 948’528 assays on 5’503 prepandemic and 34’019 copandemic samples from hospital patients and healthy blood donors. The seroprevalence increased in March 2020 (0.3%; CI 95% : 0.1% - 0.5%) among hospital patients but plateaued in April at 1.1-1.3%, and dropped to 0.3-0.7% in July. A dynamic transmission model describing SARS-CoV-2 transmission and seroconversion in the general population of the Canton of Zurich yielded an infection fatality ratio of 0.6% (CI 95% : 0.4%-0.8%), similarly to other European areas. While the evolution of seroprevalence points to a high effectiveness of containment measures, our data highlight that antibody waning warrants a continuous seromonitoring to reliably estimate the prevalence in a population.

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