SARS-CoV-2 Antibody Levels and Infections in Multiple Vaccinated Employees Over Time

This prospective cohort study aimed to monitor the humoral immune response to SARS-CoV-2 proteins over 3 years in relation to repeated vaccination or infection. Quantitative immunoassays traceable to international IgG units were used to measure and compare IgG levels against Wuhan type and Omicron spike-S1 and nucleocapsid proteins over 3 years. In addition, the Euroimmun-N-test was used to determine positive IgG values against the nucleocapsid. A total of 1223 serum samples from 126 participants without evidence of COVID-19 at enrollment were analyzed and used to calculate antibody half-lives following vaccination or infection, as reported by the questionnaire. Antibody levels and half-life against both variants of the spike S1 protein increased significantly with each additional vaccination or after infection. IgG against the Wuhan type was, on average, three times higher than against the Omicron variant. The half-lives of antibodies against the Wuhan type after the second and third vaccinations and after infection were significantly longer than those of IgG against the Omicron variant. Two-thirds of the cohort reported COVID-19 infection, detected with a sensitivity of 70% by the quantitative nucleocapsid IgG assay and 83% by the Euroimmun-N-test. The level of anti-nucleocapsid-IgG after infection in the vaccinated cohort was significantly lower than anti-S1-IgG and also lower than in unvaccinated infected persons. Despite repeated vaccinations and progressively increasing IgG antibody levels targeting the spike protein, most of the cohort reported breakthrough infections, possibly due to the lower concentration and reduced half-life of antibodies against the Omicron variant.