Diagnostic performances and thresholds: The key to harmonization in serological SARS-CoV-2 assays?
Diagnostic performances and thresholds: The key to harmonization in serological SARS-CoV-2 assays?
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DOI：
10.1016/j.cca.2020.05.050
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发表时间：
2020-10-01
影响因子：
5
通讯作者：
Sciacovelli, Laura
中科院分区：
文献类型：
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作者：
Plebani, Mario;Padoan, Andrea;Sciacovelli, Laura
背景资料：严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）特异性抗体（Ab）检测性能的评价对于建立和监测病毒在社区中的传播至关重要。在这项研究中，重点是IgG抗体，我们比较了三种荧光法（CLIA）和两种酶联免疫吸附法（ELISA）的可靠性。来自总共271名受试者的血清，包括64名逆转录-聚合酶链反应（RT-PCR）确认的SARS-CoV-2患者，使用Maglumi（Snibe），Liaison（Diasorin）、iFlash（Yhlo）、Euroimmun（Medizinische Diagnostika AG）和Wantai（Wantai Biological Pharmacy）测定。使用制造商的阈值和优化阈值评估诊断灵敏度和特异性、阳性和阴性似然比。（Maglumi 2 kAU/L，Liaison 6.2 kAU/L和iFlash 15.0 kAU/L）允许我们实现负似然比和准确度：Maglumi为0.06和93.5%; Liaison为0.03和93.1%; 0.03和91%的iFlash。所有CLIA检测的诊断敏感性和特异性分别高于93.8%和85.9%。总体一致性为90.3%（科恩的kappa = 0.805和SE = 0.041）CLIA，和98.4%（科恩的kappa = 0.962和SE = 0.126）ELISA.Conclusions：获得的结果表明，CLIA检测，它可能是可以定义阈值，提高阴性似然比。因此，阴性检测结果能够识别有感染风险的受试者，然后应随着时间的推移对其进行密切监测，以防止病毒进一步传播。此外，重新定义的阈值提高了总体检测间一致性，为更好地协调血清学检测铺平了道路。
Background: The evaluation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibody (Ab) assay performances is of the utmost importance in establishing and monitoring virus spread in the community. In this study focusing on IgG antibodies, we compare reliability of three chemiluminescent (CLIA) and two enzyme linked immunosorbent (ELISA) assays.Methods: Sera from a total of 271 subjects, including 64 reverse transcription-polymerase chain reaction (RT-PCR) confirmed SARS-CoV-2 patients were tested for specific Ab using Maglumi (Snibe), Liaison (Diasorin), iFlash (Yhlo), Euroimmun (Medizinische Labordiagnostika AG) and Wantai (Wantai Biological Pharmacy) assays. Diagnostic sensitivity and specificity, positive and negative likelihood ratios were evaluated using manufacturers' and optimized thresholds.Results: Optimized thresholds (Maglumi 2 kAU/L, Liaison 6.2 kAU/L and iFlash 15.0 kAU/L) allowed us to achieve a negative likelihood ratio and an accuracy of: 0.06 and 93.5% for Maglumi; 0.03 and 93.1% for Liaison; 0.03 and 91% for iFlash. Diagnostic sensitivities and specificities were above 93.8% and 85.9%, respectively for all CLIA assays. Overall agreement was 90.3% (Cohen's kappa = 0.805 and SE = 0.041) for CLIA, and 98.4% (Cohen's kappa = 0.962 and SE = 0.126) for ELISA.Conclusions: The results obtained indicate that, for CLIA assays, it might be possible to define thresholds that improve the negative likelihood ratio. Thus, a negative test result enables the identification of subjects at risk of being infected, who should then be closely monitored over time with a view to preventing further viral spread. Redefined thresholds, in addition, improved the overall inter-assay agreement, paving the way to a better harmonization of serologic tests.