Evaluation of pre-Omicron population immunity for SARS-CoV-2 in the Household Influenza Vaccine Evaluation (HIVE) cohort

BACKGROUND: Continued serosurvey for SARS-CoV-2 population immunity is critical for vaccine strain selection and identification of susceptible groups such as young children. We aim to evaluate the use of a high-throughput, low-volume assay to describe strain-specific IgG measurement in a longitudinally followed community based cohort. METHODS: The longitudinal Household Influenza Vaccine Evaluation study has observed around 300 households annually for acute respiratory illness. SARS-CoV-2 variant-specific IgG (including original, Delta, Beta, and Omicron variants) concentrations were measured using multiplex electrochemiluminescence (ECL), pseudoviral neutralization (PN), and ACE2 inhibition assays in participants who had serum samples drawn between July 1 and December 31, 2021. Spearman's rank correlation coefficient assessed correlation within and between ECL, ACE2, and PN assays. Receiver operating characteristic (ROC) analysis evaluated the performance of ECL and ACE2 assays. Generalized additive mixed models estimated population immunity by age against SARS-CoV-2 variants. RESULTS: A total of 156 serum samples from 117 participants were selected for this study. Most (65.8%) were from adults and a majority (77.8%) received vaccination during the analysis period. High correlations were observed within ECL IgG assays (0.95-1.00), within ACE2 inhibition assays (0.70-0.99), and between assay platforms, including ECL versus PN (0.81-0.83) and ACE2 versus PN (0.88-0.95). ROC analysis demonstrated strong discrimination of vaccination status by ECL IgG assays (AUC: 0.84-0.88; sensitivity: 0.88-0.91; specificity: 0.87-0.88). ACE2 inhibition assays showed more variable performance (AUC: 0.53-0.96; sensitivity: 0.17-0.93; specificity: 0.91-1.00), with lower performance observed for some BA.2-related antigens. SARS-CoV-2 IgG concentrations generally increased with age and appeared to plateau in early adulthood, although estimates were imprecise in younger age groups because of small sample sizes. CONCLUSION: We found a high correlation between ECL, ACE2, and PN across variants. Age-specific IgG quantities reflected behavior and infection histories collected by active surveillance.