Serological testing for SARS-CoV-2 antibodies in clinical practice: A comparative diagnostic accuracy study.
Serological testing for SARS-CoV-2 antibodies in clinical practice: A comparative diagnostic accuracy study.
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DOI：
10.1111/all.15206
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发表时间：
2022-07
期刊：
影响因子：
12.4
通讯作者：
Nagler, Michael
中科院分区：
文献类型：
--
作者：
Horn, Michael P.;Jonsdottir, Hulda R.;Brigger, Daniel;Damonti, Lauro;Suter-Riniker, Franziska;Endrich, Olga;Froehlich, Tanja K.;Fiedler, Martin;Largiader, Carlo R.;Marschall, Jonas;Weber, Benjamin;Eggel, Alexander;Nagler, Michael
关键词：
血清学试验是监测传染病和检测宿主免疫力的有力工具。然而，制造商通常提供通过偏倚研究产生的诊断准确性数据，临床实践中的性能本质上不清楚。我们的目的是确定各种血清学检测策略的诊断准确性，以（a）识别既往患有2019冠状病毒病（COVID-19）的患者和（B）预测真实的临床环境中的SARS-CoV-2中和抗体。我们前瞻性地纳入了2573名连续的医护人员和1085名在瑞士大学医院疑似或可能既往患有COVID-19的住院患者。基于不同分析技术的各种血清学免疫测定（酶联免疫吸附测定，ELISA;化学发光免疫测定，CLIA;电化学发光免疫测定，ECLIA;和侧流免疫测定，LFI），SARS-CoV-2的表位（核衣壳，N;受体结合结构域，RBD;延伸RBD，RBD+;进行刺突[S]蛋白的S1或S2结构域（S1/S2）和抗体亚型（IgG、泛IG）。鼻咽拭子真实的实时PCR检测阳性定义为既往COVID-19。在一个患者亚组（n = 201）中进行了SARS-CoV-2活病毒的中和试验，以评估中和活性。抗NECLIA（86.8%）和抗S1 ELISA（86.2%）检测既往COVID-19患者的灵敏度≥85%。抗S1/S2 CLIA、抗RBD+LFI、抗N CLIA、抗RBD ELISA和抗N ELISA的灵敏度分别为84.7%、84.0%、81.0%、79.2%和65.6%。抗N ECLIA、抗N CLIA、抗S1 ELISA、抗N ELISA、抗S1/S2 CLIA、抗RBD ELISA和抗RBD+LFI的特异性分别为98.4%、98.3%、98.2%、97.7%、97.6%、97.2%和96.1%。抗S1 ELISA（92.7%）、抗NECLIA（91.7%）、抗S1/S2 CLIA（90.3%）、抗RBD+LFI（87.9%）和抗RBD ELISA（85.8%）检测中和抗体的灵敏度≥85%。抗N CLIA的敏感性为84.1%，抗N ELISA的敏感性为66.2%。抗N CLIA（100%）、抗S1/S2 CLIA（97.7%）和抗RBD+LFI（97.9%）的特异性≥97%。抗RBD ELISA、抗N ECLIA、抗S1 ELISA和抗N ELISA的特异性分别为95.9%、93.0%、92%和65.3%。亚组间诊断准确性指标一致。在临床实践中，SARS-CoV-2抗体血清学检测的诊断准确性差异很大，识别既往COVID-19患者的灵敏度与制造商的规格存在很大差异。当使用此类检测来估计特定人群的感染负担并确定预防再感染的可能性时，应考虑此处提供的数据。这项大型前瞻性横断面研究确定了各种血清学检测策略在真实的临床环境中识别既往COVID-19患者和预测SARS-CoV-2中和抗体的诊断准确性。抗NECLIA和抗S1 ELISA检测既往COVID-19患者的诊断准确性较高（灵敏度≥85%;特异性≥97%）。抗S1/S2 CLIA和抗RBD+LFI检测中和抗体的准确度较高（灵敏度≥85%;特异性≥97%）。缩略语：CLIA，化学发光免疫测定; COVID-19，2019冠状病毒病; ECLIA，电化学发光免疫测定; ELISA，酶联免疫吸附测定; LFI，侧流免疫测定; N，核蛋白; RBD，SARS-CoV-2刺突糖蛋白的受体结合结构域; RBD+，SARS-CoV-2刺突糖蛋白的延伸受体结合结构域; SARS-CoV-2，严重急性呼吸综合征冠状病毒2型; S1/2，SARS-CoV-2刺突糖蛋白的结构域1或2
Serological tests are a powerful tool in the monitoring of infectious diseases and the detection of host immunity. However, manufacturers often provide diagnostic accuracy data generated through biased studies, and the performance in clinical practice is essentially unclear. We aimed to determine the diagnostic accuracy of various serological testing strategies for (a) identification of patients with previous coronavirus disease‐2019 (COVID‐19) and (b) prediction of neutralizing antibodies against SARS‐CoV‐2 in real‐life clinical settings. We prospectively included 2573 consecutive health‐care workers and 1085 inpatients with suspected or possible previous COVID‐19 at a Swiss University Hospital. Various serological immunoassays based on different analytical techniques (enzyme‐linked immunosorbent assays, ELISA; chemiluminescence immunoassay, CLIA; electrochemiluminescence immunoassay, ECLIA; and lateral flow immunoassay, LFI), epitopes of SARS‐CoV‐2 (nucleocapsid, N; receptor‐binding domain, RBD; extended RBD, RBD+; S1 or S2 domain of the spike [S] protein, S1/S2), and antibody subtypes (IgG, pan‐Ig) were conducted. A positive real‐time PCR test from a nasopharyngeal swab was defined as previous COVID‐19. Neutralization assays with live SARS‐CoV‐2 were performed in a subgroup of patients to assess neutralization activity (n = 201). The sensitivity to detect patients with previous COVID‐19 was ≥85% in anti‐N ECLIA (86.8%) and anti‐S1 ELISA (86.2%). Sensitivity was 84.7% in anti‐S1/S2 CLIA, 84.0% in anti‐RBD+LFI, 81.0% in anti‐N CLIA, 79.2% in anti‐RBD ELISA, and 65.6% in anti‐N ELISA. The specificity was 98.4% in anti‐N ECLIA, 98.3% in anti‐N CLIA, 98.2% in anti‐S1 ELISA, 97.7% in anti‐N ELISA, 97.6% in anti‐S1/S2 CLIA, 97.2% in anti‐RBD ELISA, and 96.1% in anti‐RBD+LFI. The sensitivity to detect neutralizing antibodies was ≥85% in anti‐S1 ELISA (92.7%), anti‐N ECLIA (91.7%), anti‐S1/S2 CLIA (90.3%), anti‐RBD+LFI (87.9%), and anti‐RBD ELISA (85.8%). Sensitivity was 84.1% in anti‐N CLIA and 66.2% in anti‐N ELISA. The specificity was ≥97% in anti‐N CLIA (100%), anti‐S1/S2 CLIA (97.7%), and anti‐RBD+LFI (97.9%). Specificity was 95.9% in anti‐RBD ELISA, 93.0% in anti‐N ECLIA, 92% in anti‐S1 ELISA, and 65.3% in anti‐N ELISA. Diagnostic accuracy measures were consistent among subgroups. The diagnostic accuracy of serological tests for SARS‐CoV‐2 antibodies varied remarkably in clinical practice, and the sensitivity to identify patients with previous COVID‐19 deviated substantially from the manufacturer's specifications. The data presented here should be considered when using such tests to estimate the infection burden within a specific population and determine the likelihood of protection against re‐infection. This large prospective cross‐sectional study determines the diagnostic accuracy of various serological testing strategies for identification of patients with previous COVID‐19 and prediction of neutralizing antibodies against SARS‐CoV‐2 in real‐life clinical settings. The diagnostic accuracy in detecting patients with previous COVID‐19 was high in anti‐N ECLIA and anti‐S1 ELISA (sensitivity ≥85%; specificity ≥97%). The accuracy in detecting neutralizing antibodies was high in anti‐S1/S2 CLIA and anti‐RBD+LFI (sensitivity ≥85%; specificity ≥97%).Abbreviations: CLIA, chemiluminescence immunoassay; COVID‐19, coronavirus disease 2019; ECLIA, electrochemiluminescence immunoassay; ELISA, enzyme‐linked immunosorbent assay; LFI, lateral flow immunoassay; N, nucleoprotein; RBD, receptor‐binding domain of the SARS‐CoV‐2 spike glycoprotein; RBD+, extended receptor‐binding domain of the SARS‐ CoV‐2 spike glycoprotein; SARS‐CoV‐2, severe acute respiratory syndrome coronavirus 2; S1/2, domain 1 or 2 of the SARS‐CoV‐2 spike glycoprotein
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影响因子：
3.5
作者：
Manthei DM;Whalen JF;Schroeder LF;Sinay AM;Li SH;Valdez R;Giacherio DA;Gherasim C
通讯作者：
Gherasim C
影响因子：
12.4
作者：
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通讯作者：
Nagler M
DOI：
10.1136/bmj.n423
发表时间：
2021-03-02
期刊：
BMJ (Clinical research ed.)
影响因子：
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作者：
Moshe M;Daunt A;Flower B;Simmons B;Brown JC;Frise R;Penn R;Kugathasan R;Petersen C;Stockmann H;Ashby D;Riley S;Atchison C;Taylor GP;Satkunarajah S;Naar L;Klaber R;Badhan A;Rosadas C;Marchesin F;Fernandez N;Sureda-Vives M;Cheeseman H;O'Hara J;Shattock R;Fontana G;Pallett SJC;Rayment M;Jones R;Moore LSP;Ashrafian H;Cherapanov P;Tedder R;McClure M;Ward H;Darzi A;Elliott P;Cooke GS;Barclay WS;React study team
通讯作者：
React study team
全国多中心对七种血清学检测方法的比较显示，SARS-CoV-2 的血清学检测结果显示，有一部分人血清学检测结果为阴性。
影响因子：
15.1
作者：
Oved K;Olmer L;Shemer-Avni Y;Wolf T;Supino-Rosin L;Prajgrod G;Shenhar Y;Payorsky I;Cohen Y;Kohn Y;Indenbaum V;Lazar R;Geylis V;Oikawa MT;Shinar E;Stoyanov E;Keinan-Boker L;Bassal R;Reicher S;Yishai R;Bar-Chaim A;Doolman R;Reiter Y;Mendelson E;Livneh Z;Freedman LS;Lustig Y
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作者：
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通讯作者：
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