Convalescent plasma therapy for the treatment of patients with COVID-19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels.
Convalescent plasma therapy for the treatment of patients with COVID-19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels.
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恢复期血浆治疗COVID-19患者：现有抗体检测方法及其与中和抗体水平的相关性评估
DOI：
10.1111/tme.12746
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发表时间：
2021-06
期刊：
影响因子：
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通讯作者：
Roberts DJ
中科院分区：
文献类型：
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作者：
Harvala H;Robb ML;Watkins N;Ijaz S;Dicks S;Patel M;Supasa P;Wanwisa D;Liu C;Mongkolsapaya J;Bown A;Bailey D;Vipond R;Grayson N;Temperton N;Gupta S;Ploeg RJ;Bolton J;Fyfe A;Gopal R;Simmonds P;Screaton G;Thompson C;Brooks T;Zambon M;Miflin G;Roberts DJ
由于缺乏批准的特定治疗药物来治疗与严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）感染相关的冠状病毒病（COVID-19），导致包括英国在内的许多国家迅速实施了恢复期血浆疗法（CPT）试验。有效的CPT可能需要恢复期献血者中高滴度的中和抗体（nAb）。了解功能性中和抗体与可扩展检测中特异性SARS-CoV-2蛋白抗体水平之间的关系对于大规模采集的成功至关重要。我们评估了中和抗体滴度是否与一系列靶向刺突（S）蛋白（人体免疫应答的主要靶标）的酶联免疫吸附试验（ELISA）中的反应性相关。从52名先前实验室确认的SARS-CoV-2感染者中采集血液样本。通过微量中和和假型测定法测定这些样品的SARS-CoV-2 nAb，并通过四种不同的ELISA测定抗体。使用受试者操作特征（ROC）分析来进一步鉴定所选测定的灵敏度和特异性，以鉴定含有高nAb水平的样品。所有样本均含有SARS-CoV-2抗体，而在43个样本（占检测样本的83%）中检测到中和抗体滴度大于1：20，在22个样本（42%）中检测到中和抗体滴度大于1：100。观察到与欧洲免疫球蛋白G（IgG）反应性的最佳相关性（斯皮尔曼Rho相关系数0.88; p < 0.001）。基于ROC分析，EUROimmun将使用9.1的反应性指数以100%特异性检测60%滴度>1：100的样品（13/22）。在几种基于ELISA的抗体检测中，nAb滴度和反应性之间存在稳健的相关性，这表明它们可能用于大规模生产含有潜在治疗水平的抗SARS-CoV-2 nAb的恢复期血浆。
The lack of approved specific therapeutic agents to treat coronavirus disease (COVID‐19) associated with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS‐CoV‐2 proteins in scalable assays will be crucial for the success of a large‐scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme‐linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. Blood samples were collected from 52 individuals with a previous laboratory‐confirmed SARS‐CoV‐2 infection. These were assayed for SARS‐CoV‐2 nAbs by microneutralisation and pseudo‐type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. All samples contained SARS‐CoV‐2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). Robust associations between nAb titres and reactivity in several ELISA‐based antibody tests demonstrate their possible utility for scaled‐up production of convalescent plasma containing potentially therapeutic levels of anti‐SARS‐CoV‐2 nAbs.