Harmonization of IgG antibody values against the SARS-CoV-2 Spike protein

The COVID-19 pandemic led to the rapid development of vaccines and diagnostic tests. To evaluate the response of IgG antibodies against the SARS-CoV-2 Spike protein in healthcare workers, a cohort study (2020-2022) was conducted in three Portuguese hospitals. Each hospital used a different assay (Abbott CMIA, Roche Elecsys ECLIA, Siemens ADVIA Centaur), which presents challenges to comparability. This study aimed to harmonize anti-S IgG levels across hospitals using a mathematical approach for combined analysis, and to estimate anti-S IgG levels over time, thus better understanding immunity dynamics. Antibody levels were measured at six time points: before vaccination, after full vaccination, 3, 6, and 12 months after the second dose, and after booster. Various harmonization strategies were tested, including WHO international conversion and quantile interpolation, followed by Deming regression. Quantile interpolation plus regression proved to be more effective than WHO conversion, preserving each hospital's data distribution and aligning the harmonized values with the Abbott CMIA used as the reference scale. After harmonization, antibody titers followed the expected trend: a sharp rise post-vaccination, a gradual decline over 12 months (659.32 BAU/mL before booster), and a notable increase after the booster (25,919.89 BAU/mL). Although cross-laboratory validation was lacking, this approach proved practical, reproducible, and promising for multicenter studies that integrate serological data from diverse platforms, at the European and global levels.