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“轻症”与“重症” COVID-19 患者的纵向抗体组库揭示了与疾病严重程度和转归相关的免疫标志物。

Longitudinal antibody repertoire in "mild" versus "severe" COVID-19 patients reveals immune markers associated with disease severity and resolution.

机构信息

Division of Viral Products, Center for Biologics Evaluation and Research (CBER), FDA, Silver Spring, MD 20871, USA.

Emergency Medical Center, Fujisawa City Hospital 2-6-1 Fujisawa, Fujisawa City, Kanagawa 251-8550, Japan.

出版信息

Sci Adv. 2021 Mar 5;7(10). doi: 10.1126/sciadv.abf2467. Print 2021 Mar.

DOI:10.1126/sciadv.abf2467
PMID:33674317
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7935365/
Abstract

Limited knowledge exists on immune markers associated with disease severity or recovery in patients with coronavirus disease 2019 (COVID-19). Here, we elucidated longitudinal evolution of SARS-CoV-2 antibody repertoire in patients with acute COVID-19. Differential kinetics was observed for immunoglobulin M (IgM)/IgG/IgA epitope diversity, antibody binding, and affinity maturation in "severe" versus "mild" COVID-19 patients. IgG profile demonstrated immunodominant antigenic sequences encompassing fusion peptide and receptor binding domain (RBD) in patients with mild COVID-19 who recovered early compared with "fatal" COVID-19 patients. In patients with severe COVID-19, high-titer IgA were observed, primarily against RBD, especially in patients who succumbed to SARS-CoV-2 infection. The patients with mild COVID-19 showed marked increase in antibody affinity maturation to prefusion SARS-CoV-2 spike that associated with faster recovery from COVID-19. This study revealed antibody markers associated with disease severity and resolution of clinical disease that could inform development and evaluation of effective immune-based countermeasures against COVID-19.

摘要

关于与 2019 年冠状病毒病（COVID-19）患者疾病严重程度或康复相关的免疫标志物，目前知识有限。在这里，我们阐明了急性 COVID-19 患者中 SARS-CoV-2 抗体库的纵向演变。在“严重”和“轻度”COVID-19 患者中，观察到免疫球蛋白 M（IgM）/IgG/IgA 表位多样性、抗体结合和亲和力成熟的差异动力学。与“致命”COVID-19 患者相比，在早期康复的轻度 COVID-19 患者中，IgG 谱显示出包含融合肽和受体结合域（RBD）的免疫优势抗原序列。在严重 COVID-19 患者中，观察到高滴度 IgA，主要针对 RBD，尤其是在死于 SARS-CoV-2 感染的患者中。轻度 COVID-19 患者对预融合 SARS-CoV-2 刺突的抗体亲和力成熟明显增加，这与 COVID-19 的快速康复有关。这项研究揭示了与疾病严重程度和临床疾病缓解相关的抗体标志物，可为开发和评估针对 COVID-19 的有效免疫对策提供信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7bbf/7935365/bd0887729ac1/abf2467-F6.jpg
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