Reinfection-Driven Accumulation of SARS-CoV-2 Antibodies: A 36-Month Longitudinal Study in Austrian Blood Donors

Background/Objectives: Long-term serological studies are essential to understand how repeated antigenic exposure affects the specific humoral immune response. The aim of this study was to investigate the long-term SARS-CoV-2 antibody dynamics in Austrian blood donors, as representatives of healthy adults, over a period of 36 months after the first SARS-CoV-2 infection. Methods: SARS-CoV-2 anti-N antibody levels were determined in more than 146,000 blood donations collected between 2020 and 2025. In addition, SARS-CoV-2 anti-N and anti-S antibody dynamics were examined in 204 individual blood donors at predefined points in time over a period of 36 months. Reinfections were inferred from increases in anti-N levels within an individual. Vaccination history and self-reported infection data were documented. Results: Anti-N seroprevalence was over 90% from the beginning of 2023 and remained at this level until 2025. Among the longitudinally observed participants, 97% had at least one serologically detected reinfection and 50% had two or more. While anti-N levels continued to increase over time, suggesting cumulative antigenic stimulation, anti-S concentrations and in vitro antibody functionality remained consistently high. Self-reported reinfections underestimated the actual incidence by a factor of six. Symptom profiles shifted toward mild respiratory manifestations, with significantly fewer cases of hyposmia or dysgeusia reported compared to the initial infection. Conclusions: After three years of observation, SARS-CoV-2 immunity is characterized by sustained antibody activity. The results show a transition from persistent, but inherently declining, to a repeatedly rebuilding, enhanced humoral immunity, indicating that SARS-CoV-2 has become endemic in Austria.