This study aimed at identifying factors influencing SARS-CoV-2-specific IgG antibody levels after vaccination and/or infection. Between January 2022 and March 2023, 2000 adults (≥18 years, Salzburg, Austria) participated in this population-based seroprevalence study by providing 3 mL of blood to detect SARS-CoV-2-specific IgG antibodies using an anti-SARS-CoV-2 IgG quantitative assay and by completing a self-designed questionnaire including anthropometric factors, vaccination information, and medical history. For 77 of the participants, a time-course study up to 24 weeks post vaccination or quarantine end was performed. Convalescent-only subjects had the lowest median antibody titer (65.6 BAU/mL) compared to vaccinated and hybrid immunized subjects (p-value < 0.0001) The type of vaccine as well as vaccine combinations significantly influenced the levels of SARS-CoV-2 spike-protein-specific IgG, ranging from a median antibody level of 770.5 BAU/mL in subjects who were vaccinated only to 3020.0 BAU/mL in hybrid immunized subjects (p-value < 0.0001). Over time, a significant decline in the levels of neutralizing antibodies was found. Depending on the subpopulation analyzed, further significant influencing factors included sex assigned at birth, disease severity, chronic diseases, and medication. A hybrid immunization resulted in more robust immune responses. Nevertheless, there were multiple other factors impacting these responses. This knowledge should be included in future vaccination strategies and serve as a guide in the development of personalized medicine.

Hormones, such as DHEA, cortisol, testosterone, and progesterone play an important part in the regulation of the human immune system. However, the exact role of endocrine factors in the production of antibodies, in this case SARS-CoV-2-specific antibodies, remains poorly understood. We investigated the association between hormone levels and SARS-CoV-2 spike-protein-specific IgG antibody titers in a large, diverse cohort of 861 vaccinated as well as vaccinated plus COVID-19 recovered individuals. We observed negative correlations between cortisol, progesterone, testosterone (in males), and SARS-CoV-2-specific antibody levels. In contrast, a positive correlation was found between DHEA and antibody titers in vaccinated males. These hormone-antibody relationships exhibited important sex-specific differences. Our findings demonstrate that hormonal factors are associated with modulating the antibody response to SARS-CoV-2, with implications for personalized approaches to vaccination and treatment. Furthermore, the wide variability in hormone levels within the healthy population also suggests the potential value of incorporating endocrine assessments into COVID-19 risk profiling. Further research is needed to fully elucidate the mechanistic underpinnings of these hormone-antibody relationships and explore their broader clinical applications in the context of the ongoing COVID-19 endemic.