Background: 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.
Methods: 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.
Findings: Among 1600 participants with longitudinal antibody follow-up, 133 reinfections were observed during a median of 22 weeks at risk. Each tenfold (log10) 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.
Interpretation: 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.
Keywords: COVID-19; Cohort study; Correlate of protection; Reinfection; Spike antibody.
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