W. Harry Feinstone Department of Molecular Microbiology and Immunology.
Department of Biochemistry and Molecular Biology.
J Clin Invest. 2020 Nov 2;130(11):6141-6150. doi: 10.1172/JCI142004.
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.
恢复期血浆是治疗 2019 年冠状病毒病（COVID-19）的主要方法，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，使用带有 Vero-E6-TMPRSS2 细胞的严重急性呼吸系统综合征冠状病毒 2（SARS-CoV-2）病毒中和测定法评估了体液免疫应答；使用商业 IgG 和 IgA ELISA 来检测刺突（S）蛋白 S1 结构域（EUROIMMUN）；IgA、IgG 和 IgM 间接 ELISA 来检测全长 S 蛋白或 S 受体结合域（S-RBD）；以及 IgG 亲和力测定法。我们使用多元线性回归和预测模型来评估抗体反应与人口统计学和临床特征之间的相关性。在总人口中，S1、全长 S 和 S-RBD 的 IgG 滴度均高于 IgM 或 IgA 滴度。在 126 个血浆样本中，有 101 个（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 确认了 95%-98%的 nAb 阳性样本，但仍有 20%-32%的 nAb 阴性样本 IgG ELISA 呈阳性。男性、年龄较大以及因 COVID-19 住院与血清学检测中的抗体反应增加有关。潜在恢复期血浆供体之间的抗体反应存在很大的异质性，但性别、年龄和住院治疗成为可以用来识别具有高可能性产生强大抗病毒抗体反应的个体的因素。
