Several tests based on chemiluminescence immunoassay techniques have become available to test for SARS-CoV-2 antibodies. There is currently insufficient data on serology assay performance beyond 35 days after symptoms onset. We aimed to evaluate SARS-CoV-2 antibody tests on three widely used platforms. A chemiluminescent microparticle immunoassay (CMIA; Abbott Diagnostics, USA), a luminescence immunoassay (LIA; Diasorin, Italy), and an electrochemiluminescence immunoassay (ECLIA; Roche Diagnostics, Switzerland) were investigated. In a multigroup study, sensitivity was assessed in a group of participants with confirmed SARS-CoV-2 (), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e., healthy blood donors, , and healthcare workers, ). Receiver operating characteristic (ROC) curves, multilevel likelihood ratios (LR), and positive (PPV) and negative (NPV) predictive values were characterized. Finally, analytical specificity was characterized in samples with evidence of the Epstein–Barr virus (EBV) (), cytomegalovirus (CMV) (), and endemic common-cold coronavirus infections () taken prior to the current SARS-CoV-2 pandemic. The diagnostic accuracy was comparable in all three assays (AUC 0.98). Using the manufacturers’ cut-offs, the sensitivities were 90%, 95% confidence interval [84,94] (LIA), 93% [88,96] (CMIA), and 96% [91,98] (ECLIA). The specificities were 99.5% [98.9,99.8] (CMIA), 99.7% [99.3,99.9] (LIA), and 99.9% [99.5,99.98] (ECLIA). The LR at half of the manufacturers’ cut-offs were 60 (CMIA), 82 (LIA), and 575 (ECLIA) for positive and 0.043 (CMIA) and 0.035 (LIA, ECLIA) for negative results. ECLIA had higher PPV at low pretest probabilities than CMIA and LIA. No interference with EBV or CMV infection was observed, whereas endemic coronavirus in some cases provided signals in LIA and/or CMIA. Although the diagnostic accuracy of the three investigated assays is comparable, their performance in low-prevalence settings is different. Introducing gray zones at half of the manufacturers’ cut-offs is suggested, especially for orthogonal testing approaches that use a second assay for confirmation.

中文翻译：

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三种不同的化学发光法检测SARS-CoV-2抗体的特征

基于化学发光免疫分析技术的几种测试可用于测试SARS-CoV-2抗体。目前尚无足够的关于症状发作后超过35天的血清学检测性能的数据。我们旨在评估在三个广泛使用的平台上的SARS-CoV-2抗体测试。研究了化学发光微粒免疫分析（CMIA；美国Abbott Diagnostics），发光免疫分析（LIA；意大利Diasorin）和电化学发光免疫分析（ECLIA； Roche Diagnostics，瑞士）。在一项多组研究中，对确诊为SARS-CoV-2的一组参与者进行了敏感性评估（），而在没有COVID-19证据的两组参与者（即健康献血者，，和医护人员，）。表征了接收器工作特性（ROC）曲线，多级似然比（LR），正（PPV）和负（NPV）预测值。最后，在样品中鉴定了分析特异性，并证明了爱泼斯坦-巴尔病毒（EBV）（），巨细胞病毒（CMV）（）和地方性普通感冠状病毒感染（）在当前SARS-CoV-2大流行之前采取。在所有三种测定中，诊断准确性均相当（AUC 0.98）。使用制造商的临界值，灵敏度分别为90％，95％置信区间[84,94]（LIA），93％[88,96]（CMIA）和96％[91,98]（ECLIA）。特异性为99.5％[98.9,99.8]（CMIA），99.7％[99.3,99.9]（LIA）和99.9％[99.5,99.98]（ECLIA）。制造商临界值的一半时，LR的阳性结果为60（CMIA），82（LIA）和575（ECLIA），阴性结果为0.043（CMIA）和0.035（LIA，ECLIA）。与较低的CMIA和LIA相比，ECLIA的PPV在较低的前测概率下更高。没有观察到对EBV或CMV感染的干扰，而在某些情况下，地方性冠状病毒在LIA和/或CMIA中提供了信号。尽管这三种研究方法的诊断准确性相当，它们在低流行设置中的表现是不同的。建议在制造商临界值的一半处引入灰色区域，尤其是对于使用第二种方法进行确认的正交测试方法。