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.

中文翻译：

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来自高通量变异特异性 SARS-CoV-2 抗刺突 IgG 和 ACE2 中和试验的抗体水平与大量人群的 COVID 感染风险相关


背景 SARS-CoV-2 抗体水平已被提议作为感染保护 （CoP） 的相关性。然而，在现实世界条件下，将具有成本效益的可扩展抗体措施作为感染预测指标的大规模前瞻性研究是有限的。我们检查了使用高通量变体特异性 SARS-CoV-2 抗刺突免疫球蛋白 G （IgG） 和 ACE2 中和测定测量的抗体水平是否与基于细胞的中和抗体 （NAb） 测量相关，以及它们是否可以作为 SARS-CoV-2 感染的合理 CoP。方法 我们在 2022 年 1 月至 2023 年 3 月期间进行了一项大型机构队列研究。参与者 （n=2,513） 提供了干血斑 （DBS） 样本，用于使用高通量测定法评估抗刺突 IgG 和 ACE2 抑制水平。使用血清样本 （n=105） 与基于真实细胞的 SARS-CoV-2 NAb 检测进行比较。评估抗体水平与感染风险之间的关联。研究结果血清和 DBS 采样以及基于细胞的中和和高通量抗体结合测定之间的抗加标 IgG 和 ACE2 中和之间的相关性都很高，尽管相关程度因变体而异。纵向评估表明，基于 DBS 的 IgG 和 ACE2 抑制水平与感染风险呈反相关，ACE2 抑制和变体匹配测量的敏感性更高。IgG 和 ACE2 抑制水平均随着时间的推移而降低，在最近启动事件为感染与疫苗接种的参与者中观察到更持久的反应。 解释结果表明，变体特异性 SARS-CoV-2 抗体水平可能是感染的有用 CoP，这对疫苗接种建议和评估感染风险具有重要意义。通过 DBS 测量的高通量检测可能在人群或个体层面的加强剂时间方面具有实用性。