Evaluation of Orthogonal Testing Algorithm for Detection of SARS-CoV-2 IgG Antibodies
Evaluation of Orthogonal Testing Algorithm for Detection of SARS-CoV-2 IgG Antibodies
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DOI：
10.1093/clinchem/hvaa210
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发表时间：
2020-12-01
影响因子：
9.3
通讯作者：
Babic, Nikolina
中科院分区：
文献类型：
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作者：
Xu, Gang;Emanuel, Anthony J.;Babic, Nikolina
背景技术背景：严重急性呼吸系统综合征冠状病毒2型（SARS-CoV-2）抗体检测是评估大流行进展、追踪接触者和识别2019冠状病毒病（COVID-19）康复患者的重要工具。我们评估了一个正交试验算法（OTA），以提高测试特异性，在这些usecases.METHODS：一个两步OTA被应用于个人谁最初测试呈阳性进行了第二次测试。在130份样本中验证了检测病毒核衣壳蛋白IgG抗体的一线检测，在148份样本中验证了检测病毒刺突蛋白IgG抗体的二线检测。在4333份临床患者标本中评价了OTA。从我们的整个患者群体数据中评估了相对于SARS-CoV-2 PCR阳性率的血清阳性率结果：一线检测的敏感性为96.4%（95% CI; 82.3%至99.4%），特异性为99.0%（95% CI; 94.7%至99.8%），而二线试验的敏感性为100%（95% CI; 87.1%至100%），特异性为98.4%（95% CI; 94.2%至99.5%）。使用OTA，78/98（80%）最初阳性的SARS-CoV-2 IgG结果通过二线检测得到确认，而11/42（26%）先前诊断的COVID-19患者在PCR诊断后94天内没有可检测到的抗体。我们的结果表明，OTA可用于识别因潜在的SARS CoV-2 IgG假阳性结果而需要进一步随访的患者。此外，血清学检测可能不够敏感，无法可靠地检测既往COVID-19感染。
BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing is an important tool in assessment of pandemic progress, contact tracing, and identification of recovered coronavirus disease 2019 (COVID-19) patients. We evaluated an orthogonal testing algorithm (OTA) to improve test specificity in these use cases.METHODS: A two-step OTA was applied where individuals who initially tested positive were tested with a second test. The first-line test, detecting IgG antibodies to the viral nucleocapsid protein, was validated in 130 samples and the second-line test, detecting IgG antibodies to the viral spike protein in 148 samples. The OTA was evaluated in 4333 clinical patient specimens. The seropositivity rates relative to the SARS-CoV-2 PCR positivity rates were evaluated from our entire patient population data (n = 5102).RESULTS: The first-line test resulted in a clinical sensitivity of 96.4% (95% CI; 82.3% to 99.4%), and specificity of 99.0% (95% CI; 94.7% to 99.8%), whereas the second-line test had a sensitivity of 100% (95% CI; 87.1% to 100%) and specificity of 98.4% (95% CI; 94.2% to 99.5%). Using the OTA, 78/98 (80%) of initially positive SARS-CoV-2 IgG results were confirmed with a second-line test, while 11/42 (26%) of previously diagnosed COVID-19 patients had no detectable antibodies as long as 94 days post PCR diagnosis.CONCLUSION: Our results show that an OTA can be used to identify patients who require further follow-up due to potential SARS CoV-2 IgG false positive results. In addition, serological testing may not be sufficiently sensitive to reliably detect prior COVID-19 infection.