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对严重和非严重 COVID-19 患者的四种 SARS-CoV-2 重组抗原的体液反应进行全面、纵向分析。

A comprehensive, longitudinal analysis of humoral responses specific to four recombinant antigens of SARS-CoV-2 in severe and non-severe COVID-19 patients.

机构信息

Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.

Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu, China.

出版信息

PLoS Pathog. 2020 Sep 10;16(9):e1008796. doi: 10.1371/journal.ppat.1008796. eCollection 2020 Sep.

Abstract

There is an urgent need for effective treatment and preventive vaccine to contain this devastating global pandemic, which requires a comprehensive understanding of humoral responses specific to SARS-CoV-2 during the disease progression and convalescent phase of COVID-19 patients. We continuously monitored the serum IgM and IgG responses specific to four SARS-CoV-2 related antigens, including the nucleoprotein (NP), receptor binding domain (RBD), S1 protein, and ectodomain (ECD) of the spike protein among non-severe and severe COVID-19 patients for seven weeks since disease onset. Most patients generated humoral responses against NP and spike protein-related antigens but with their distinct kinetics profiles. Combined detection of NP and ECD antigens as detecting antigen synergistically improved the sensitivity of the serological assay, compared to that of using NP or RBD as detection antigen. 80.7% of convalescent sera from COVID-19 patients revealed that the varying extents of neutralization activities against SARS-CoV-2. S1-specific and ECD-specific IgA responses were strongly correlated with the neutralization activities in non-severe patients, but not in severe patients. Moreover, the neutralizing activities of the convalescent sera were shown to significantly decline during the period between 21 days to 28 days after hospital discharge, accompanied by a substantial drop in RBD-specific IgA response. Our data provide evidence that are crucial for serological testing, antibody-based intervention, and vaccine design of COVID-19.

摘要

目前迫切需要有效的治疗方法和预防性疫苗来控制这一致命的全球大流行,这需要全面了解 COVID-19 患者疾病进展和康复阶段针对 SARS-CoV-2 的体液反应。我们连续监测了非重症和重症 COVID-19 患者自发病以来七周内针对四种 SARS-CoV-2 相关抗原的血清 IgM 和 IgG 反应,包括核衣壳蛋白(NP)、受体结合域(RBD)、S1 蛋白和刺突蛋白的胞外域(ECD)。大多数患者针对 NP 和刺突蛋白相关抗原产生了体液反应,但具有不同的动力学特征。与使用 NP 或 RBD 作为检测抗原相比,联合检测 NP 和 ECD 抗原作为检测抗原可协同提高血清学检测的灵敏度。80.7%的 COVID-19 患者的恢复期血清显示对 SARS-CoV-2 的中和活性存在不同程度的差异。S1 特异性和 ECD 特异性 IgA 反应与非重症患者的中和活性强烈相关,但与重症患者无关。此外,恢复期血清的中和活性在出院后 21 天至 28 天期间显著下降,同时 RBD 特异性 IgA 反应大幅下降。我们的数据为 COVID-19 的血清学检测、基于抗体的干预和疫苗设计提供了至关重要的证据。

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