Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
Department of Medicine, Washington University School of Medicine, St. Louis, MO.
Clin Chem. 2020 Dec 1;66(12):1538-1547. doi: 10.1093/clinchem/hvaa211.
Commercially available SARS-CoV-2 serological assays based on different viral antigens have been approved for the qualitative determination of anti-SARS-CoV-2 antibodies. However, there are limited published data associating the results from commercial assays with neutralizing antibodies.
Sixty-six specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys Anti-SARS-CoV-2, Abbott SARS-CoV-2 IgG, or EUROIMMUN SARS-CoV-2 IgG assays and 5 control specimens were analyzed for the presence of neutralizing antibodies to SARS-CoV-2. Correlation, concordance, positive percent agreement (PPA), and negative percent agreement (NPA) were calculated at several cutoffs. Results were compared in patients categorized by clinical outcomes.
The correlation between SARS-CoV-2 neutralizing titer (EC50) and the Roche, Abbott, and EUROIMMUN assays was 0.29, 0.47, and 0.46, respectively. At an EC50 of 1:32, the concordance kappa with Roche was 0.49 (95% CI; 0.23-0.75), with Abbott was 0.52 (0.28-0.77), and with EUROIMMUN was 0.61 (0.4-0.82). At the same neutralizing titer, the PPA and NPA for the Roche was 100% (94-100) and 56% (30-80); Abbott was 96% (88-99) and 69% (44-86); and EUROIMMUN was 91% (80-96) and 81% (57-93) for distinguishing neutralizing antibodies. Patients who were intubated, had cardiac injury, or acute kidney injury from COVID-19 infection had higher neutralizing titers relative to those with mild symptoms.
COVID-19 patients generate an antibody response to multiple viral proteins such that the calibrator ratios on the Roche, Abbott, and EUROIMMUN assays are all associated with SARS-CoV-2 neutralization. Nevertheless, commercial serological assays have poor NPA for SARS-CoV-2 neutralization, making them imperfect proxies for neutralization.
基于不同病毒抗原的市售 SARS-CoV-2 血清学检测已获准用于定性检测抗 SARS-CoV-2 抗体。然而，将商业检测结果与中和抗体相关联的已发表数据有限。
分析了 48 例经 PCR 确诊的 COVID-19 患者的 66 份标本，这些患者的罗氏 Elecsys Anti-SARS-CoV-2、雅培 SARS-CoV-2 IgG 或 EUROIMMUN SARS-CoV-2 IgG 检测结果均为阳性，以及 5 份对照标本，以检测其对 SARS-CoV-2 的中和抗体。在几个截止值处计算了 SARS-CoV-2 中和效价（EC50）与罗氏、雅培和 EUROIMMUN 检测之间的相关性、一致性、阳性百分比一致率（PPA）和阴性百分比一致率（NPA）。比较了按临床结局分类的患者的结果。
SARS-CoV-2 中和效价（EC50）与罗氏、雅培和 EUROIMMUN 检测的相关性分别为 0.29、0.47 和 0.46。在 EC50 为 1:32 时，与罗氏的一致性 Kappa 为 0.49（95%CI；0.23-0.75），与雅培的为 0.52（0.28-0.77），与 EUROIMMUN 的为 0.61（0.4-0.82）。在相同的中和效价下，罗氏的 PPA 和 NPA 分别为 100%（94-100）和 56%（30-80）；雅培为 96%（88-99）和 69%（44-86）；EUROIMMUN 为 91%（80-96）和 81%（57-93），用于区分中和抗体。与症状较轻的患者相比，因 COVID-19 感染而插管、有心脏损伤或急性肾损伤的患者中和效价更高。
COVID-19 患者会产生针对多种病毒蛋白的抗体反应，因此罗氏、雅培和 EUROIMMUN 检测的校准器比值均与 SARS-CoV-2 中和相关。然而，商业血清学检测对 SARS-CoV-2 中和的 NPA 较差，使其不能作为中和的完美替代物。
