Temporal Analysis of Serial Donations Reveals Decrease in Neutralizing Capacity and Justifies Revised Qualifying Criteria for Coronavirus Disease 2019 Convalescent Plasma
Temporal Analysis of Serial Donations Reveals Decrease in Neutralizing Capacity and Justifies Revised Qualifying Criteria for Coronavirus Disease 2019 Convalescent Plasma
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DOI：
10.1093/infdis/ijaa803
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发表时间：
2021-03-01
影响因子：
6.4
通讯作者：
McDonough, Kathleen A.
中科院分区：
文献类型：
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作者：
Girardin, Roxie C.;Dupuis, Alan P., II;McDonough, Kathleen A.
背景。2019冠状病毒病（COVID-19）恢复期血浆（CCP）获得了美国食品和药物管理局（FDA）的紧急使用授权。使用体外严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）免疫球蛋白G （IgG）测试（OVSARS2IgG）的信号与切断比为>= 12的CCP允许标记为“高效价”。OVSARS2IgG比值与血浆/血清对真性sars - cov的中和能力之间的关系尚不清楚。对196例初次捐献后0 ~ 119天的重复CCP供者981例样本进行分析。使用金标准空斑减少中和试验（PRNT）评估感染性病毒减少50% （PRNT50）和90% （PRNT90）的中和能力。用OVSARS2IgG对91例献血者进行评估，并与PRNT滴度进行比较，以确定诊断的准确性。捐献标本中，32.7%/79.5% （PRNT90/PRNT50）的初始滴度达到1:80，但只有14.0%/48.8% （PRNT90/PRNT50）的滴度达到临界值>= 85 DPID。OVSARS2IgG结果与中和能力的相关性允许外推CCP治疗结果。与治疗有益组相比，OVSARS2IgG比例相等的CCP的中和滴度为>= 1:640 （PRNT50）和/或>= 1:80 （PRNT90）。OVSARS2IgG对高度中和性CCP的特异性和阳性预测值是最佳的，使用比例显著大于FDA的截止值。该信息为改进用于治疗COVID-19的CCP推荐特性提供了基础。
Background. Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) received an Emergency Use Authorization by the US Food and Drug Administration (FDA). CCP with a signal-to-cutoff ratio of >= 12 using the Ortho VITROS severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) test (OVSARS2IgG) is permitted to be labeled "high titer." Little is known about the relationship between OVSARS2IgG ratio and neutralizing capacity of plasma/sera against genuine SARS-CoV-2.Methods. Nine hundred eighty-one samples from 196 repeat CCP donors 0-119 days post-initial donation (DPID) were analyzed. Neutralizing capacity was assessed for 50% (PRNT50) and 90% (PRNT90) reduction of infectious virus using the gold standard plaque reduction neutralization test (PRNT). A subset of 91 donations was evaluated by OVSARS2IgG and compared to PRNT titers for diagnostic accuracy.Results. Of donations, 32.7%/79.5% (PRNT90/PRNT50) met a 1:80 titer initially but only 14.0%/48.8% (PRNT90/PRNT50) met this cutoff >= 85 DPID. Correlation of OVSARS2IgG results to neutralizing capacity allowed extrapolation to CCP therapy results. CCP with OVSARS2IgG ratios equivalent to a therapeutically beneficial group had neutralizing titers of >= 1:640 (PRNT50) and/or >= 1:80 (PRNT90). Specificity and positive predictive value of the OVSARS2IgG for qualifying highly neutralizing CCP was optimal using ratios significantly greater than the FDA cutoff.Conclusions. This information provides a basis for refining the recommended properties of CCP used to treat COVID-19.