Background: SARS-CoV-2 antibody levels have been proposed as a correlate of protection (CoP) from infection. Yet, large-scale prospective studies of cost-effective scalable antibody measures as predictors of infection under real-world conditions are limited. We examined whether antibody levels measured using high-throughput variant-specific SARS-CoV-2 anti-spike immunoglobulin G (IgG) and ACE2-neutralization assays correlate with cell-based neutralizing antibody (NAb) measurements, and whether they can serve as a reasonable CoP from SARS-CoV-2 infection.
Methods: We conducted a large, institutional cohort study between January 2022 and March 2023. Participants (n=2,513) provided dried blood spot (DBS) samples for assessment of anti-spike IgG and ACE2 inhibition levels using high-throughput assays. Comparison with authentic cell-based SARS-CoV-2 NAb assays was conducted using serum samples (n=105). Associations between antibody levels and risk of infection were evaluated.
Findings: Correlation between serum and DBS sampling, and cell-based neutralizing and high-throughput antibody binding assays, was high for both anti-spike IgG and ACE2 neutralization, though the degree of correlation varied by variant. Longitudinal evaluation suggested both DBS-based IgG and ACE2 inhibition levels were anticorrelated with infection risk, with higher sensitivity noted for ACE2 inhibition and variant-matched measures. Both IgG and ACE2 inhibition levels decreased over time, with more durable responses observed in participants whose most recent priming event was infection versus vaccination.
Interpretation: Findings suggest that variant-specific SARS-CoV-2 antibody levels may be a useful CoP for infection, which has important implications for vaccination recommendations and evaluating infection risk. High-throughput assays measured via DBS may have utility in timing of boosters, either at the population or an individual level.
Keywords: SARS-CoV-2; antibodies; antibody detection; correlates of protection; infection risk.
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