Anti-SARS-CoV-2 IgG Cut-off Value for Predicting Neutralizing Antibodies and Reinfection Risk in Natural and Hybrid Immunity: A Longitudinal Observational Study.

Understanding immune responses to SARS-CoV-2, particularly the dynamics of natural versus hybrid immunity (infection plus vaccination), is essential for shaping public health strategies. A prospective cohort of 171 adults with mild to moderate COVID-19 was followed from February to July 2021. Participants were grouped as having natural (without COVID-19 vaccination, n=129) or hybrid (vaccinated before and/or after infection, n=42) immunity. Anti-RBD IgG and neutralizing antibodies were measured at the 1st, 3rd, and 6th months. ROC analysis identified an IgG cut-off to predict neutralizing antibody positivity. Reinfections were monitored for 12 months. Hybrid immunity was associated with significantly higher IgG levels across all time points. IgG and NAb levels were strongly correlated (r=0.86 at 1st, r=0.80 at 3rd month). An IgG threshold of 303.8 AU/mL predicted NAb positivity with 91.9% sensitivity and 90% specificity. Reinfection occurred in 4.6% of participants during the Omicron wave, often despite high antibody levels. An IgG level ≥303.8 AU/mL is a strong predictor of NAb positivity and can serve as a practical surrogate marker of functional immunity, especially where neutralization testing is unavailable. Reinfections despite high IgG/NAb levels highlight the limitations of static thresholds, particularly against different variants.