Spike antibody levels and risk of SARS-CoV-2 reinfection: a two-year cohort study in previously infected adults

The need for a validated correlate of protection (CoP) for SARS-CoV-2 remains unmet, particularly in immunosuppressed or vulnerable populations. Antibody quantification is widely available, but the relationship with reinfection risk remains uncertain. We conducted a two-year cohort study in Denmark including 2960 adults with previous SARS-CoV-2 infection and more than 9000 plasma samples collected between 2020 and 2022. Spike antibody concentrations were measured using the Roche Elecsys® Anti-SARS-CoV-2 S assay. Weekly antibody levels were modelled by nonlinear mixed-effect models and linked to reinfection risk using a competing-risk Cox regression explicitly adjusted for infection pressure and individual testing frequency. Among 1600 participants with longitudinal antibody follow-up, 133 reinfections were observed during a median of 22 weeks at risk. Each tenfold (log 10 ) increase in spike antibody level was associated with a 28 % reduction in reinfection hazard (HR 0.72, 95 % CI 0.57–0.90, p = 0.0045). This effect was consistent across multiple sensitivity analyses and robust to fluctuations in infection pressure and testing practices. No discrete antibody threshold was identified, suggesting a continuous, dose-response association between antibody concentration and protection. Higher spike antibody levels were consistently associated with lower risk of SARS-CoV-2 reinfection, supporting their use as continuous markers of protection. Although assay-specific and without a single protective cutoff, antibody measurements may help monitor patient groups prone to poor vaccine responses—such as those receiving chemotherapy or immune-modulating drugs—and guide individualized revaccination once immune competence recovers. • Spike antibody levels inversely associate with SARS-CoV-2 reinfection risk. • Danish cohort study links national registries with antibody measurements. • Competing-risk model explicitly adjusts for weekly infection pressure fluctuations. • Results support individualized revaccination strategies based on antibody levels.