Three Years After COVID-19 Vaccination, Anti-Spike SARS-CoV-2 Antibody Concentration Decreases and Is Accompanied by Increasing Anti-Nucleocapsid Seropositivity

Background/Objectives: The anti-spike (S) SARS-CoV-2 antibodies confer neutralizing properties and their concentration may be related to COVID-19 protection. Anti-nucleocapsid (N) SARS-CoV-2 antibodies in mRNA COVID-19 vaccine recipients indicate infection. The aim of this study was to analyze the anti-S and anti-N titers 3 years after COVID-19 vaccination. Methods: Ninety-nine vaccinated healthcare workers provided blood samples in 2024 and filled out questionnaires about their COVID-19 history and boosters acceptance. Anti-spike and anti-nucleocapsid IgG were assessed with commercially available immunoassays, DiaSorin’s SARS-CoV-2 TrimericS IgG and Abbott’s SARS-CoV-2 IgG, respectively. Results: Three years after the primary COVID-19 vaccination, the anti-S SARS-CoV-2 antibody concentration was still high. However, it dropped in comparison to the data obtained a year before (3600 vs. 2040 BAU/mL), possibly due to the lack of boosters. In contrast, the percentage of anti-N seropositive individuals grew from 34% two years after vaccination to 40.4% after three years. Subjects with SARS-CoV-2 infection within a year prior to the antibody measurements had statistically significantly higher median anti-S concentrations than those with tentatively no contact with SARS-CoV-2 (2940 vs. 1930 BAU/mL). Conclusions: Overall, our data indicates that although the booster vaccinations’ acceptance decreases, the circulating SARS-CoV-2 stimulates humoral immunity, resulting in high anti-S antibody concentrations even three years after the vaccination.