Variant-Specific Kinetics of SARS-CoV-2 Anti-Nucleocapsid Antibodies and Household Transmission in Families During Anchestral, Alpha, Delta and Omicron Periods

To investigate SARS-CoV-2 antibody kinetics and household transmission, infected children along with their families were tested for anti-nucleocapsid antibodies at 1, 3, 6, 9 and 12 months post-SARS-CoV-2 infection during the Ancestral, Alpha, Delta, and Omicron waves. We prospectively included SARS-CoV-2 acute infected children (n = 189). After household recruitment (n = 76 households), the total study population was 228 children and 105 adults. The median age (IQR) of children and adults was 96 (115) months and 504 (96) months, respectively. Anti-nucleocapsid (anti-N) COI (cut-off index) titers peaked at three months post-infection and declined thereafter (<i>p</i>-value < 0.001), and 89.2% remained seropositive at 12 months. Children displayed significantly higher anti-N COI titers than adults during the Delta (<i>p</i>-value: 0.018) and Omicron (<i>p</i>-value: 0.047) periods. Household contact anti-N positivity (evidence of infection) was associated with pediatric index cases (aOR: 1.61, 95% CI: 1.11-2.35; <i>p</i>-value: 0.013) and elevated early anti-N COI titers (aOR: 1.24 per log₁₀ unit, 95% CI: 1.05-1.48; <i>p</i>-value: 0.011). Higher secondary attacks were detected in Delta (aOR: 2.12, 95% CI: 1.19-3.77; <i>p</i>-value: 0.011) and Omicron (aOR: 2.75, 95% CI: 1.44-5.25; <i>p</i>-value: 0.002) compared to Ancestral. Waning of SARS-CoV-2 anti-N titers was faster in secondary cases (aHR: 1.62, 95% CI: 1.01-2.59; <i>p</i>-value: 0.047, Cox model) and during Omicron infection (aHR: 1.74 vs. Ancestral, 95% CI: 1.08-2.79; <i>p</i>-value: 0.023). In contrast, waning was slower in SARS-CoV-2 cases with higher baseline anti-N COI titers (aHR: 0.77, 95% CI: 0.64-0.93; <i>p</i>-value: 0.011). These findings demonstrate variant-specific, age-dependent antibody kinetics, emphasizing that pediatric index cases were associated with higher odds of household infection.