Background SARS-CoV-2 antibody levels have been proposed as a correlate of protection 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 by high-throughput variant-specific SARS-CoV-2 anti-spike immunoglobulin G (IgG) and angiotensin-converting enzyme 2 (ACE2) neutralization assays correlate with cell-based neutralizing antibody measurements and whether they can serve as a reasonable correlate of protection from SARS-CoV-2 infection. Methods We conducted a large institutional cohort study between January 2022 and March 2023. Participants (N = 2513) provided dried blood spot (DBS) samples for assessment of anti-spike IgG and ACE2 inhibition levels through high-throughput assays. Comparison with authentic cell-based SARS-CoV-2 neutralizing antibody assays was conducted with serum samples (n = 105). Associations between antibody levels and risk of infection were evaluated. Results Correlation between serum and DBS sampling and between cell-based neutralizing and high-throughput antibody binding assays was high for anti-spike IgG and ACE2 neutralization, though the degree of correlation varied by variant. Longitudinal evaluation suggested that DBS-based IgG and ACE2 inhibition levels were anticorrelated with infection risk, with higher sensitivity noted for ACE2 inhibition and variant-matched measures. IgG and ACE2 inhibition levels decreased over time, with more durable responses observed in participants whose most recent priming event was infection vs vaccination. Conclusions Findings suggest that variant-specific SARS-CoV-2 antibody levels may be a useful correlate of protection 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 at the population or individual level.

中文翻译：

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高通量变异特异性 SARS-CoV-2 抗刺突免疫球蛋白 G 和血管紧张素转换酶 2 中和试验的抗体水平与大量人群的 COVID-19 感染风险相关


背景 SARS-CoV-2 抗体水平已被提议作为预防感染的相关性。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。我们检查了通过高通量变体特异性 SARS-CoV-2 抗刺突免疫球蛋白 G （IgG） 和血管紧张素转换酶 2 （ACE2） 中和试验测量的抗体水平是否与基于细胞的中和抗体测量相关，以及它们是否可以作为保护 SARS-CoV-2 感染的合理相关性。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 = 2513） 提供了干血斑 （DBS） 样本，用于通过高通量测定评估抗刺突 IgG 和 ACE2 抑制水平。用血清样本 （n = 105） 与基于真实细胞的 SARS-CoV-2 中和抗体测定进行比较。评估抗体水平与感染风险之间的关联。结果 血清和 DBS 采样之间以及基于细胞的中和和高通量抗体结合测定之间的抗刺突 IgG 和 ACE2 中和的相关性很高，尽管相关性程度因变体而异。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 抑制和变异匹配测量的敏感性更高。IgG 和 ACE2 抑制水平随着时间的推移而下降，在最近启动事件是感染与疫苗接种的参与者中观察到更持久的反应。 结论 研究结果表明，变体特异性 SARS-CoV-2 抗体水平可能是感染保护的有用相关性，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对人群或个体水平的加强针时间有用。