Accuracy of serological testing for SARS-CoV-2 antibodies: First results of a large mixed-method evaluation study.
Accuracy of serological testing for SARS-CoV-2 antibodies: First results of a large mixed-method evaluation study.
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作者：
Brigger D;Horn MP;Pennington LF;Powell AE;Siegrist D;Weber B;Engler O;Piezzi V;Damonti L;Iseli P;Hauser C;Froehlich TK;Villiger PM;Bachmann MF;Leib SL;Bittel P;Fiedler M;Largiadèr CR;Marschall J;Stalder H;Kim PS;Jardetzky TS;Eggel A;Nagler M
需要能够识别对SARS-CoV-2的保护性免疫的血清学免疫分析，以适应检疫措施，评估疫苗接种反应，并评估供者血浆。然而，到目前为止，这种免疫分析的实用性仍然不清楚。在一项混合设计的评估研究中，我们比较了基于各种SARS-CoV-2蛋白的血清学免疫分析的诊断准确性，并评估了患者血清中抗体的中和活性。从2018/2019年冬季开始，与医务人员和生物库样本一起对连续入院的确诊SARS-CoV-2患者进行前瞻性跟踪。建立了一种利用SARS-CoV-2刺突蛋白重组受体结合域(RBD)的内部酶联免疫吸附试验，并与三种针对核蛋白(N)、刺突蛋白S1结构域(S1)和基于全长刺突蛋白的侧向流动免疫分析(LFI)的商业应用的酶联免疫吸附试验(ELISA)进行了比较。用活的SARS-CoV-2进行中和试验。纳入1,477人，包括112SARS-CoV-2阳性(定义为实时聚合酶链式反应阳性；患病率为7.6%)。免疫球蛋白血清转换发生在第0天至第21天之间。ELISA对RBD、S1和N蛋白的敏感性分别为88.4%、89.3%和72.9%，特异性均在94%以上。在54例SARS-CoV-2阳性个体中，96.3%的人在血清对≥1：16稀释度时对活的SARS-CoV-2有完全中和作用，而6份SARS-CoV-2阴性血清均未显示中和活性。针对SARS-CoV-2的RBD和S1蛋白的ELISA是一种有前景的免疫检测方法，将在验证对SARS-CoV-2的诊断准确性和保护性免疫的研究中进一步评估。与LFI相比，抗S1、RBD和N的ELISA具有更高的准确性。96.4%的阳性患者血清显示SARS-CoV-2完全中和活的SARS-CoV-2。缩写：ELISA，酶联免疫吸附试验；LFI，横向流动免疫分析；S_1，S_1结构域；S，S_1；SENS，敏感性；SPEC，特异性；RBD，S蛋白的受体结合域；N，核衣壳蛋白。
Serological immunoassays that can identify protective immunity against SARS‐CoV‐2 are needed to adapt quarantine measures, assess vaccination responses, and evaluate donor plasma. To date, however, the utility of such immunoassays remains unclear. In a mixed‐design evaluation study, we compared the diagnostic accuracy of serological immunoassays that are based on various SARS‐CoV‐2 proteins and assessed the neutralizing activity of antibodies in patient sera. Consecutive patients admitted with confirmed SARS‐CoV‐2 infection were prospectively followed alongside medical staff and biobank samples from winter 2018/2019. An in‐house enzyme‐linked immunosorbent assay utilizing recombinant receptor‐binding domain (RBD) of the SARS‐CoV‐2 spike protein was developed and compared to three commercially available enzyme‐linked immunosorbent assays (ELISAs) targeting the nucleoprotein (N), the S1 domain of the spike protein (S1), and a lateral flow immunoassay (LFI) based on full‐length spike protein. Neutralization assays with live SARS‐CoV‐2 were performed. One thousand four hundred and seventy‐seven individuals were included comprising 112 SARS‐CoV‐2 positives (defined as a positive real‐time PCR result; prevalence 7.6%). IgG seroconversion occurred between day 0 and day 21. While the ELISAs showed sensitivities of 88.4% for RBD, 89.3% for S1, and 72.9% for N protein, the specificity was above 94% for all tests. Out of 54 SARS‐CoV‐2 positive individuals, 96.3% showed full neutralization of live SARS‐CoV‐2 at serum dilutions ≥ 1:16, while none of the 6 SARS‐CoV‐2‐negative sera revealed neutralizing activity. ELISAs targeting RBD and S1 protein of SARS‐CoV‐2 are promising immunoassays which shall be further evaluated in studies verifying diagnostic accuracy and protective immunity against SARS‐CoV‐2. 1477 individuals are tested with 4 different serological SARS‐CoV‐2 immunoassays. ELISA against S1, RBD and N show superior accuracy compared to LFI against S. 96.4% of patient sera that are positive in ELISA show full neutralization of live SARS‐CoV‐2. Abbreviations: ELISA, enzyme‐linked immunosorbent assay; LFI, lateral flow immunoassay; S1, S1 domain of the spike protein; S, spike protein; sens, sensitivity; spec, specificity; RBD, receptor‐binding domain of the spike protein; N, nucleocapsid protein.
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影响因子：
5.2
作者：
Doehla, M.;Boesecke, C.;Streeck, H.
通讯作者：
Streeck, H.
238例住院患者严重急性呼吸综合征冠状病毒2（SARS-CoV-2）血清学检测初步研究
影响因子：
5.8
作者：
Liu, Lei;Liu, Wanbing;Zheng, Shangen
通讯作者：
Zheng, Shangen
DOI：
10.3390/v6082991
发表时间：
2014-08-07
期刊：
Viruses
影响因子：
--
作者：
McBride R;van Zyl M;Fielding BC
通讯作者：
Fielding BC
影响因子：
19
作者：
Haveri, Anu;Smura, Teemu;Savolainen-Kopra, Carita
通讯作者：
Savolainen-Kopra, Carita
影响因子：
5.4
作者：
Bosch, BJ;van der Zee, R;Rottier, PJM
通讯作者：
Rottier, PJM