基于实验室的SARS-CoV-2抗体检测方法在性能上差异很大。然而,关于测定性能的前瞻性收集数据有限,和最少的临床信息,以指导不同结果的解释。
在2周内,提交临床SARS-CoV-2IgG测试的1080份连续血浆样本平行测试抗核衣壳IgG(抗N,雅培)和抗刺药IgG(抗S1,EUROIMMUN)。对任一测定均呈阳性或边界线的样品进行了图表审查,以及年龄/性别匹配的样本队列,两种检测均为阴性。CDC监测病例定义用于确定临床敏感性/特异性并进行受试者工作特征曲线分析。
两种方法都有52个样本呈阳性,2仅对反N为阳性,34仅抗S1阳性,和反S1的27条边界线。在单独抗S1阳性的34个人中,8人(24%)已确认COVID-19。没有抗S1临界病例抗N阳性或确诊/可能的COVID-19。抗N检测的敏感性较低(84.2%[95%CI72.1-92.5%]vs94.7%[95%CI85.4-98.9%]),但特异性更强(99.2%[95%CI95.5-100%]vs86.9%[95%CI79.6-92.3%])。如果指数阈值从1.4降低到0.6,雅培的抗N敏感性可以提高到96.5%,对特异性的影响最小。
不同血清学测定之间的真实世界一致性可能低于先前在回顾性研究中描述的。这些发现对SARS-CoV-2IgG结果的解释具有重要意义。特别是随着尖峰抗原靶向疫苗的出现,作为真正感染的患者的子集,抗N阴性和抗S1阳性。
Laboratory-based methods for SARS-CoV-2 antibody detection vary widely in performance. However, there are limited prospectively-collected data on assay performance, and minimal clinical information to guide interpretation of discrepant results.
Over a 2-week period, 1080 consecutive plasma samples submitted for clinical SARS-CoV-2 IgG testing were tested in parallel for anti-
nucleocapsid IgG (anti-N, Abbott) and anti-spike IgG (anti-S1, EUROIMMUN). Chart review was conducted for samples testing positive or borderline on either assay, and for an age/sex-matched cohort of samples negative by both assays. CDC surveillance
case definitions were used to determine clinical sensitivity/specificity and conduct receiver operating characteristics curve analysis.
There were 52 samples positive by both methods, 2 positive for anti-N only, 34 positive for anti-S1 only, and 27 borderline for anti-S1. Of the 34 individuals positive for anti-S1 alone, 8 (24%) had confirmed COVID-19. No anti-S1 borderline cases were positive for anti-N or had confirmed/probable COVID-19. The anti-N assay was less sensitive (84.2% [95% CI 72.1-92.5%] vs 94.7% [95% CI 85.4-98.9%]) but more specific (99.2% [95% CI 95.5-100%] vs 86.9% [95% CI 79.6-92.3%]) than anti-S1. Abbott anti-N sensitivity could be improved to 96.5% with minimal effect on specificity if the index threshold was lowered from 1.4 to 0.6.
Real-world concordance between different serologic assays may be lower than previously described in retrospective studies. These findings have implications for the interpretation of SARS-CoV-2 IgG results, especially with the advent of spike antigen-targeted vaccination, as a subset of patients with true infection are anti-N negative and anti-S1 positive.