Zentrallabor, Kantonsspital Graubünden, Loësstrasse 170, 7000 Chur, Switzerland.
Liechtensteinisches Landesspital, Heiligkreuz, 9490 Vaduz, Liechtenstein.
Biomed Res Int. 2020 Nov 16;2020:9878453. doi: 10.1155/2020/9878453. eCollection 2020.
Knowledge of the sensitivities of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody tests beyond 35 days after the clinical onset of COVID-19 is insufficient. We aimed to describe positivity rate of SARS-CoV-2 assays employing three different measurement principles over a prolonged period. Two hundred sixty-eight samples from 180 symptomatic patients with COVID-19 and a reverse transcription polymerase chain reaction (RT-PCR) test followed by serological investigation of SARS-CoV-2 antibodies were included. We conducted three chemiluminescence (including electrochemiluminescence assay (ECLIA)), four enzyme-linked immunosorbent assay (ELISA), and one lateral flow immunoassay (LFIA) test formats. Positivity rates, as well as positive (PPVs) and negative predictive values (NPVs), were calculated for each week after the first clinical presentation for COVID-19. Furthermore, combinations of tests were assessed within an orthogonal testing approach employing two independent assays and predictive values were calculated. Heat maps were constructed to graphically illustrate operational test characteristics. During a follow-up period of more than 9 weeks, chemiluminescence assays and one ELISA IgG test showed stable positivity rates after the third week. With the exception of ECLIA, the PPVs of the other chemiluminescence assays were ≥95% for COVID-19 only after the second week. ELISA and LFIA had somewhat lower PPVs. IgM exhibited insufficient predictive characteristics. An orthogonal testing approach provided PPVs ≥ 95% for patients with a moderate pretest probability (e.g., symptomatic patients), even for tests with a low single test performance. After the second week, NPVs of all but IgM assays were ≥95% for patients with low to moderate pretest probability. The confirmation of negative results using an orthogonal algorithm with another assay provided lower NPVs than the single assays. When interpreting results from SARS-CoV-2 tests, the pretest probability, time of blood draw, and assay characteristics must be carefully considered. An orthogonal testing approach increases the accuracy of positive, but not negative, predictions.
关于严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）抗体检测在 COVID-19 临床发病后 35 天以上的敏感性，目前了解不足。本研究旨在描述采用三种不同测量原理的 SARS-CoV-2 检测在较长时间内的阳性率。我们纳入了 180 例有症状的 COVID-19 患者的 268 份样本，这些患者均接受了逆转录聚合酶链反应（RT-PCR）检测，随后对 SARS-CoV-2 抗体进行了血清学调查。我们进行了三种化学发光（包括电化学发光测定法（ECLIA））、四种酶联免疫吸附测定法（ELISA）和一种侧向流动免疫测定法（LFIA）的检测格式。计算了每位患者首次出现 COVID-19 症状后每一周的阳性率（PPV）和阴性预测值（NPV）。此外，采用两种独立的检测方法，通过正交检测方法评估了检测组合，并计算了预测值。构建热图以图形方式说明操作检测特征。在超过 9 周的随访期间，化学发光检测和一种 ELISA IgG 检测在第三周后显示出稳定的阳性率。除 ECLIA 外，其他化学发光检测的 PPV 在第二周后仅针对 COVID-19 时均≥95%。ELISA 和 LFIA 的 PPV 略低。IgM 显示出不足的预测特征。正交检测方法为具有中度先验概率（例如，有症状的患者）的患者提供了≥95%的 PPV，即使是对于单项检测性能较低的检测方法也是如此。对于先验概率较低至中度的患者，除 IgM 检测外，所有检测的 NPV 在第二周后均≥95%。使用另一种检测方法进行正交算法确认阴性结果会比单项检测产生更低的 NPV。在解释 SARS-CoV-2 检测结果时，必须仔细考虑先验概率、采血时间和检测特征。正交检测方法可提高阳性预测的准确性，但不能提高阴性预测的准确性。
