Landesspital Liechtenstein, Heiligkreuz, 9490 Vaduz, Liechtenstein.
Central Laboratory, Kantonsspital Graubünden, Loësstrasse 170, 7000 Chur, Switzerland.
Dis Markers. 2021 Jan 6;2021:8810196. doi: 10.1155/2021/8810196. eCollection 2021.
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 ( = 145), whereas specificity was determined in two groups of participants without evidence of COVID-19 (i.e., healthy blood donors, = 191, and healthcare workers, = 1002). 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) ( = 9), cytomegalovirus (CMV) ( = 7), and endemic common-cold coronavirus infections ( = 12) 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.
已有多种基于化学发光免疫分析技术的检测方法可用于检测 SARS-CoV-2 抗体。目前，对于症状出现后 35 天以上的血清学检测性能，仍缺乏足够的数据。本研究旨在评估三种广泛使用的平台上 SARS-CoV-2 抗体检测的性能。检测使用了一种化学发光微粒子免疫分析（CMIA；雅培诊断，美国）、一种发光免疫分析（LIA；DiaSorin，意大利）和一种电化学发光免疫分析（ECLIA；罗氏诊断，瑞士）。在一项多组研究中，对一组经确认的 SARS-CoV-2 感染者（n = 145）评估了敏感性，而在两组无 COVID-19 证据的参与者中（即健康献血者，n = 191 和医护人员，n = 1002）评估了特异性。对受试者工作特征（ROC）曲线、多水平似然比（LR）和阳性（PPV）及阴性（NPV）预测值进行了描述。最后，在当前 SARS-CoV-2 大流行之前采集的证据表明有 EBV（n = 9）、CMV（n = 7）和地方性普通感冒冠状病毒感染的样本（n = 12）中，对分析特异性进行了描述。三种检测方法的诊断准确性相当（AUC 0.98）。使用制造商的截止值，敏感性分别为 90%（95%置信区间[84，94]）（LIA）、93%（88，96]（CMIA）和 96%（91，98]（ECLIA）。特异性分别为 99.5%（98.9，99.8]（CMIA）、99.7%（99.3，99.9]（LIA）和 99.9%（99.5，99.98]（ECLIA）。在制造商截止值的一半处，阳性结果的 LR 分别为 60（CMIA）、82（LIA）和 575（ECLIA），阴性结果的 LR 分别为 0.043（CMIA）和 0.035（LIA、ECLIA）。ECLIA 在低预测试概率时的阳性预测值高于 CMIA 和 LIA。未观察到 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 中产生了信号。尽管三种检测方法的诊断准确性相当，但在低流行率环境下，其性能不同。建议在制造商截止值的一半处引入灰色区域，特别是对于使用第二种检测方法进行确认的正交检测方法。
