Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
J Clin Microbiol. 2020 Dec 17;59(1). doi: 10.1128/JCM.01892-20.
Sensitive and specific severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serologic assays are needed to inform diagnostic, therapeutic, and public health decision-making. We evaluated three commercial serologic assays as stand-alone tests and as components of two-test algorithms. Two nucleocapsid antibody tests (Abbott IgG and Roche total antibody) and one spike protein antibody test (DiaSorin IgG) were included. We assessed sensitivity using 128 serum samples from symptomatic PCR-confirmed coronavirus disease 2019 (COVID-19)-infected patients and specificity using 1,204 samples submitted for routine serology prior to COVID-19's emergence, plus 64 pandemic-era samples from SARS-CoV-2 PCR-negative patients with respiratory symptoms. Assays were evaluated as stand-alone tests and as components of a two-test algorithm in which positive results obtained using one assay were verified using a second assay. The two nucleocapsid antibody tests were more sensitive than the spike protein antibody test overall (70% and 70% versus 57%; ≤ 0.003), with pronounced differences observed using samples collected 7 to 14 days after symptom onset. All three assays were comparably sensitive (≥89%; ≥ 0.13) using samples collected >14 days after symptom onset. Specificity was higher using the nucleocapsid antibody tests (99.3% and 99.7%) than using the spike protein antibody test (97.8%; ≤ 0.002). When any two assays were paired in a two-test algorithm, the specificity was 99.9% ( < 0.0001 to 0.25 compared with the individual assays), and the positive predictive value (PPV) improved substantially, with a minimal effect on the negative predictive value (NPV). In conclusion, two nucleocapsid antibody tests outperformed a spike protein antibody test. Pairing two different serologic tests in a two-test algorithm improves the PPV, compared with the individual assays alone, while maintaining the NPV.
需要灵敏且特异的严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）血清学检测方法，以辅助诊断、治疗和公共卫生决策。我们评估了三种商业血清学检测方法，将其作为单独的检测方法，以及两种检测方法的组成部分。其中包括两种核衣壳抗体检测（雅培 IgG 和罗氏总抗体）和一种刺突蛋白抗体检测（DiaSorin IgG）。我们使用 128 份来自症状性经 PCR 确诊的 2019 冠状病毒病（COVID-19）感染患者的血清样本评估了敏感性，使用 COVID-19 出现前提交的 1204 份常规血清学样本和 64 份大流行时期来自呼吸道症状但 SARS-CoV-2 PCR 阴性患者的样本评估了特异性。评估了这些检测方法作为单独的检测方法和两种检测方法的组成部分，其中一种检测方法的阳性结果使用另一种检测方法进行验证。两种核衣壳抗体检测的敏感性总体上均高于刺突蛋白抗体检测（70%和 70%对 57%； ≤ 0.003），在症状出现后 7 至 14 天采集的样本中观察到明显差异。所有三种检测方法在症状出现后 >14 天采集的样本中，其敏感性均相当（≥89%； ≥ 0.13）。使用核衣壳抗体检测的特异性（99.3%和 99.7%）高于使用刺突蛋白抗体检测的特异性（97.8%； ≤ 0.002）。当两种检测方法中的任意两种在两种检测方法的算法中配对时，特异性为 99.9%（ < 0.0001 至 0.25，与单独的检测方法相比），阳性预测值（PPV）显著提高，而对阴性预测值（NPV）的影响很小。总之，两种核衣壳抗体检测方法优于刺突蛋白抗体检测方法。与单独使用个体检测方法相比，在两种检测方法的算法中配对两种不同的血清学检测方法可提高 PPV，同时保持 NPV。
