The emergence of SARS-CoV-2 variants that evade immune responses poses challenges to effective prevention. We prospectively enrolled 111 COVID-19 patients in Thailand (2021-2022), who received homologous or heterologous vaccines or were unvaccinated. Plasma neutralizing antibody (nAb) levels against SARS-CoV-1 and 13 SARS-CoV-2 strains were measured using a multiplex surrogate virus neutralization test (sVNT) assay within a year. nAb levels increased in two weeks, showing strong inhibition against ancestral SARS-CoV-2 and non-omicron variants, but not against SAR-CoV-1 and lower responses to omicron variants. nAb levels declined by the day 60. Breakthrough patients with heterologous vaccines had higher nAb levels compared to other groups. nAb levels were lower in breakthrough patients with pneumonia than those with other conditions. Notably, breakthrough patients aged ≥60 showed rapid declines in antibody levels. Our findings highlight diverse immune responses influenced by immunization, age, and clinical conditions, underscoring the need for tailored vaccination strategies against evolving variants.