Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population.
Sex, age, and hospitalization drive antibody responses in a COVID-19 convalescent plasma donor population.
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DOI：
10.1172/jci142004
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发表时间：
2020-11-02
期刊：
影响因子：
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通讯作者：
Tobian, Aaron Ar
中科院分区：
文献类型：
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作者：
Klein, Sabra L;Pekosz, Andrew;Tobian, Aaron Ar
恢复期血浆是目前COVID-19的主要治疗方法之一，但缺乏确定治疗效果的数据。需要对潜在血浆供体的抗体应答进行全面分析，并了解驱动变异抗体应答的临床和人口统计学因素。在126名潜在的恢复期血浆供体中，通过使用Vero-E6-TMPRSS 2细胞的SARS-CoV-2病毒中和试验、针对S蛋白S1结构域的商业IgG和伊加ELISA（Euroimmun）、针对全长S或S受体结合结构域的伊加、IgG和IgM间接ELISA（S-RBD）以及IgG亲合力试验来评价体液免疫应答。采用多元线性回归和预测模型评估抗体应答与人口统计学和临床特征之间的相关性。在总体人群中，S1、全长S和S-RBD的IgG滴度均大于IgM或伊加。在126份血浆样本中，101份（80%）具有可检测的中和滴度。以中和效价为参照，IgG ELISA的灵敏度为95- 98%，但特异性仅为20- 32%。在血清学检测中，男性、年龄较大和因COVID-19住院均与抗体应答增加一致相关。与总体抗体应答相反，中和抗体滴度随时间降低。在潜在的恢复期血浆捐献者中，抗体反应存在很大的异质性，但性别、年龄和住院情况可作为识别具有高抗病毒抗体水平的可能性的因素。恢复期血浆是2019冠状病毒病（COVID-19）的主要治疗方法，但缺乏确定其治疗效果的数据。在126名潜在的恢复期血浆供体中，使用严重急性呼吸综合征冠状病毒2型评估体液免疫应答使用Vero-E6-TMPRSS 2细胞的SARS-CoV-2病毒中和试验;用于检测刺突（S）蛋白S1结构域的商业IgG和伊加ELISA（EUROIMMUN）;伊加、IgG和IgM间接ELISA以检测全长S蛋白或S受体结合结构域（S-RBD）;和IgG亲合力测定。我们使用多元线性回归和预测模型来评估抗体应答与人口统计学和临床特征之间的相关性。总人群中S1、全长S和S-RBD的IgG滴度均大于IgM或伊加滴度。在126份血浆样本中，101份（80%）具有可检测的中和抗体（nAb）滴度。使用nAb滴度作为参考，IgG ELISA确认95%-98%的nAb阳性样品，但20%-32%的nAb阴性样品仍为IgG ELISA阳性。在血清学检测中，男性、年龄较大和因COVID-19住院与抗体反应增加相关。在潜在的恢复期血浆捐献者中，抗体应答存在很大的异质性，但性别、年龄和住院情况可作为因素用于识别具有强抗病毒抗体应答的高可能性的个体。
Convalescent plasma is currently one of the leading treatments for COVID-19, but there is a paucity of data identifying therapeutic efficacy. A comprehensive analysis of the antibody responses in potential plasma donors and an understanding of the clinical and demographic factors that drive variant antibody responses is needed. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated by a SARS-CoV-2 virus neutralization assay using Vero-E6-TMPRSS2 cells, commercial IgG and IgA ELISA to Spike (S) protein S1 domain (Euroimmun), IgA, IgG and IgM indirect ELISAs to the full-length S or S-receptor binding domain (S-RBD), and an IgG avidity assay. Multiple linear regression and predictive models were utilized to assess the correlations between antibody responses with demographic and clinical characteristics. IgG titers were greater than either IgM or IgA for S1, full length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing titers. Using neutralization titer as the reference, the sensitivity of the IgG ELISAs ranged between 95-98%, but specificity was only 20-32%. Male sex, older age, and hospitalization with COVID-19 were all consistently associated with increased antibody responses across the serological assays. Neutralizing antibody titers were reduced over time in contrast to overall antibody responses. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody levels.Convalescent plasma is a leading treatment for coronavirus disease 2019 (COVID-19), but there is a paucity of data identifying its therapeutic efficacy. Among 126 potential convalescent plasma donors, the humoral immune response was evaluated using a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus neutralization assay with Vero-E6-TMPRSS2 cells; a commercial IgG and IgA ELISA to detect the spike (S) protein S1 domain (EUROIMMUN); IgA, IgG, and IgM indirect ELISAs to detect the full-length S protein or S receptor-binding domain (S-RBD); and an IgG avidity assay. We used multiple linear regression and predictive models to assess the correlations between antibody responses and demographic and clinical characteristics. IgG titers were greater than either IgM or IgA titers for S1, full-length S, and S-RBD in the overall population. Of the 126 plasma samples, 101 (80%) had detectable neutralizing antibody (nAb) titers. Using nAb titers as the reference, the IgG ELISAs confirmed 95%-98% of the nAb-positive samples, but 20%-32% of the nAb-negative samples were still IgG ELISA positive. Male sex, older age, and hospitalization for COVID-19 were associated with increased antibody responses across the serological assays. There was substantial heterogeneity in the antibody response among potential convalescent plasma donors, but sex, age, and hospitalization emerged as factors that can be used to identify individuals with a high likelihood of having strong antiviral antibody responses.