Department of Transfusion Medicine, Ulm University, Ulm, Germany;
Institute for Clinical Transfusion Medicine and Immunogenetics, German Red Cross Blood Transfusion Service Baden-Württemberg-Hessen and University Hospital Ulm, Ulm, Germany.
J Immunol. 2021 Jun 1;206(11):2614-2622. doi: 10.4049/jimmunol.2100036. Epub 2021 May 12.
The current SARS-CoV-2 pandemic has triggered the development of various SARS-CoV-2 neutralization tests. A wild-type virus (using African green monkey VeroE6 cells), a pseudovirus (using human Caco-2 cells), and a surrogate neutralization test platform were applied to characterize the SARS-CoV-2 neutralization potential of a cohort of 111 convalescent plasma donors over a period of seven months after diagnosis. This allowed an in-depth validation and assay performance analysis of these platforms. More importantly, we found that SARS-CoV-2 neutralization titers were stable or even increased within the observation period, which contradicts earlier studies reporting a rapid waning of Ab titers after three to four months. Moreover, we observed a positive correlation of neutralization titers with increasing age, number of symptoms reported, and the presence of the Rhesus Ag RhD. Validation of the platforms revealed that highest assay performances were obtained with the wild-type virus and the surrogate neutralization platforms. However, our data also suggested that selection of cutoff titers had a strong impact on the evaluation of neutralization potency. When taking strong neutralization potency, as demonstrated by the wild-type virus platform as the gold standard, up to 55% of plasma products had low neutralization titers. However, a significant portion of these products were overrated in their potency when using the surrogate assay with the recommended cutoff titer. In summary, our study demonstrates that SARS-CoV-2 neutralization titers are stable for at least seven months after diagnosis and offers a testing strategy for rapid selection of high-titer convalescent plasma products in a biosafety level 1 environment.
当前的 SARS-CoV-2 大流行引发了各种 SARS-CoV-2 中和测试的发展。我们应用野生型病毒（使用非洲绿猴 VeroE6 细胞）、假病毒（使用人 Caco-2 细胞）和替代中和测试平台，对 111 名康复期血浆捐献者在诊断后七个月的时间内的 SARS-CoV-2 中和潜力进行了特征描述。这使得我们能够深入验证和分析这些平台的检测性能。更重要的是，我们发现 SARS-CoV-2 中和滴度在观察期内是稳定的，甚至有所增加，这与早期研究报告的在三到四个月后 Ab 滴度迅速下降的结论相矛盾。此外，我们观察到中和滴度与年龄增加、报告的症状数量以及 Rh 阳性（Rhesus Ag RhD）的存在呈正相关。对这些平台的验证表明，野生型病毒和替代中和平台具有最高的检测性能。然而，我们的数据还表明，选择截断值对中和效力的评估有很大影响。当以野生型病毒平台作为金标准来评估强中和效力时，高达 55%的血浆产品具有低中和滴度。然而，当使用推荐的截断值的替代检测时，这些产品中的很大一部分在效力上被高估了。总之，我们的研究表明，SARS-CoV-2 中和滴度在诊断后至少七个月内是稳定的，并提供了一种在生物安全一级环境中快速筛选高滴度康复期血浆产品的检测策略。
