Characteristics of SARS-CoV-2 Reinfection and Ancestral RBD-Blocking Antibody Levels: A Cross-Sectional Study in the Post-Zero-COVID Era from Shanghai

Background: SARS-CoV-2 reinfections increased substantially after the emergence of Omicron variants. Methods: We conducted a cross-sectional study of 2095 individuals with prior Omicron BA.2 infection in Shanghai, China, during the early post-zero-COVID period. Data on demographics, infection history, and lifestyle factors were collected via questionnaire, and blood samples were obtained for ancestral RBD-blocking antibody measurement. Results: Meeting WHO physical activity recommendations (≥600 MET-min/week) was associated with lower reinfection odds (OR = 0.59, 95% CI: 0.46–0.74, p < 0.001). The overall median ancestral RBD-blocking antibody level was 263.93 U/mL (IQR: 36.41–331.87). Older age was associated with lower ancestral RBD-blocking antibody levels (β = –0.0038 per year, 95% bootstrap CI: –0.0057 to –0.0019, p < 0.001). All vaccinated groups had significantly higher ancestral RBD-blocking antibody levels than unvaccinated individuals: partially vaccinated (β = 0.4440, 95% CI: 0.1569 to 0.6830, p < 0.001), fully vaccinated (β = 0.8516, 95% CI: 0.7464 to 0.9595, p < 0.001), homologous booster (β = 1.0297, 95% CI: 0.9408 to 1.1223, p < 0.001), and heterologous booster (β = 1.0838, 95% CI: 0.9387 to 1.2226, p < 0.001). Time since last immune event was inversely associated with ancestral RBD-blocking antibody levels (β = –0.0232 per month, 95% CI: –0.0385 to –0.0077, p = 0.0031). Conclusions: In this cross-sectional study, meeting WHO physical activity recommendations was associated with 41% lower odds of SARS-CoV-2 reinfection, although reverse causality cannot be ruled out. All vaccinated groups had higher ancestral RBD-blocking antibody levels than unvaccinated individuals. Older age and longer time since last immune event were associated with lower ancestral RBD-blocking antibody levels. These associations need confirmation in prospective, well-powered studies.