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COVID-19 恢复期血浆捐献者候选人中针对 SARS-CoV-2 的中和抗体的临床、实验室和时间预测因素。

Clinical, laboratory, and temporal predictors of neutralizing antibodies against SARS-CoV-2 among COVID-19 convalescent plasma donor candidates.

机构信息

Department of Medicine, University of Washington, Seattle, Washington, USA.

Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

出版信息

J Clin Invest. 2021 Feb 1;131(3). doi: 10.1172/JCI144930.

Abstract

BACKGROUNDSARS-CoV-2-specific antibodies may protect from reinfection and disease, providing rationale for administration of plasma containing SARS-CoV-2-neutralizing antibodies (nAbs) as a treatment for COVID-19. Clinical factors and laboratory assays to streamline plasma donor selection, and the durability of nAb responses, are incompletely understood.METHODSPotential convalescent plasma donors with virologically documented SARS-CoV-2 infection were tested for serum IgG against SARS-CoV-2 spike protein S1 domain and against nucleoprotein (NP), and for nAb.RESULTSAmong 250 consecutive persons, including 27 (11%) requiring hospitalization, who were studied a median of 67 days since symptom onset, 97% were seropositive on 1 or more assays. Sixty percent of donors had nAb titers ≥1:80. Correlates of higher nAb titers included older age (adjusted OR [AOR] 1.03 per year of age, 95% CI 1.00-1.06), male sex (AOR 2.08, 95% CI 1.13-3.82), fever during illness (AOR 2.73, 95% CI 1.25-5.97), and disease severity represented by hospitalization (AOR 6.59, 95% CI 1.32-32.96). Receiver operating characteristic analyses of anti-S1 and anti-NP antibody results yielded cutoffs that corresponded well with nAb titers, with the anti-S1 assay being slightly more predictive. nAb titers declined in 37 of 41 paired specimens collected a median of 98 days (range 77-120) apart (P < 0.001). Seven individuals (2.8%) were persistently seronegative and lacked T cell responses.CONCLUSIONnAb titers correlated with COVID-19 severity, age, and sex. SARS-CoV-2 IgG results can serve as useful surrogates for nAb testing. Functional nAb levels declined, and a small proportion of convalescent individuals lacked adaptive immune responses.FUNDINGThe project was supported by the Frederick National Laboratory for Cancer Research with support from the NIAID under contract number 75N91019D00024, and was supported by the Fred Hutchinson Joel Meyers Endowment, Fast-Grants, a New Investigator award from the American Society for Transplantation and Cellular Therapy, and NIH contracts 75N93019C0063, 75N91019D00024, and HHSN272201800013C, and NIH grants T32-AI118690, T32-AI007044, K08-AI119142, and K23-AI140918.

摘要

背景

SARS-CoV-2 特异性抗体可能具有预防再次感染和疾病的作用,这为使用含有 SARS-CoV-2 中和抗体 (nAb) 的血浆作为 COVID-19 的治疗方法提供了依据。临床因素和实验室检测方法可简化血浆供者选择,以及 nAb 反应的持久性,但目前尚不完全了解。

方法

对经病毒学证实的 SARS-CoV-2 感染的潜在恢复期血浆供者进行血清 IgG 针对 SARS-CoV-2 刺突蛋白 S1 结构域和核蛋白 (NP) 的检测,以及 nAb 检测。

结果

在 250 名连续患者中,包括 27 名(11%)需要住院的患者,自症状发作以来中位时间为 67 天,97%的患者在 1 项或多项检测中呈血清阳性。60%的供者具有 nAb 滴度≥1:80。较高 nAb 滴度的相关因素包括年龄较大(校正后比值比 [AOR] 每增加 1 岁为 1.03,95%CI 为 1.00-1.06)、男性(AOR 2.08,95%CI 为 1.13-3.82)、发热(AOR 2.73,95%CI 为 1.25-5.97)和以住院表示的疾病严重程度(AOR 6.59,95%CI 为 1.32-32.96)。抗 S1 和抗 NP 抗体结果的受试者工作特征分析得出的截止值与 nAb 滴度吻合良好,抗 S1 检测略具有更好的预测性。在中位间隔 98 天(范围 77-120)采集的 41 对配对标本中,有 37 份(37%)的 nAb 滴度下降(P<0.001)。7 名个体(2.8%)持续血清阴性且缺乏 T 细胞反应。

结论

nAb 滴度与 COVID-19 严重程度、年龄和性别相关。SARS-CoV-2 IgG 结果可作为 nAb 检测的有用替代指标。功能性 nAb 水平下降,少数恢复期个体缺乏适应性免疫反应。

经费

该项目由美国国立癌症研究所弗雷德里克实验室资助,得到美国国立卫生研究院传染病与过敏研究所合同号 75N91019D00024 的支持,并得到弗雷德·哈钦森癌症研究中心乔尔·迈耶斯纪念基金会、快速拨款、美国移植和细胞治疗学会新研究员奖以及 NIH 合同 75N93019C0063、75N91019D00024 和 HHSN272201800013C 的支持,以及 NIH 资助 T32-AI118690、T32-AI007044、K08-AI119142 和 K23-AI140918。

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