Dynamics of B-cell repertoires and emergence of cross-reactive responses in COVID-19 patients with different disease severity.-猫眼课题宝

DOI：

10.2139/ssrn.3751051

发表时间：

2020-07

期刊：

ArXiv

影响因子：

通讯作者：

中科院分区：

其他

文献类型：

作者：

Zachary Montague;Huibin Lv;J. Otwinowski;William S. DeWitt;G. Isacchini;Garrick K. Yip;Wilson W. Ng;O. Tsang;M. Yuan;Hejun Liu;I. Wilson;J. Peiris;N. Wu;Armita Nourmohammad;C. K. Mok

新冠肺炎患者表现出不同的疾病严重程度，从没有症状到需要重症监护。虽然已经鉴定了一些抗SARS-CoV-2的单抗，但我们仍然缺乏对新冠肺炎患者B细胞受体(Bcr)谱系的整体情况的了解。在这里，我们使用在感染期间收集的多个时间点的BCR谱系的高通量测序来表征19名不同疾病严重程度的患者的B细胞对SARS-CoV-2的统计和动态反应特征。基于原则性统计方法，我们确定了与不同疾病严重程度相关的BCR的差异序列特征。我们确定了34个在患者中共享的显着扩大的罕见克隆谱系，作为对SARS-CoV-2的特定反应的候选。此外，我们在一些患者中发现了对SARS-CoV和SARS-CoV-2具有交叉反应的BCR的自然出现。总体而言，我们的结果为开发合理的新冠肺炎治疗方法和疫苗提供了重要的见解。

COVID-19 patients show varying severity of the disease ranging from asymptomatic to requiring intensive care. Although a number of monoclonal antibodies against SARS-CoV-2 have been identified, we still lack an understanding of the overall landscape of B-cell receptor (BCR) repertoires in COVID-19 patients. Here, we used high-throughput sequencing of BCR repertoires collected over multiple time points during an infection to characterize statistical and dynamical signatures of the B-cell response to SARS-CoV-2 in 19 patients with different disease severities. Based on principled statistical approaches, we determined differential sequence features of BCRs associated with different disease severity. We identified 34 significantly expanded rare clonal lineages shared among patients as candidates for a specific response to SARS-CoV-2. Moreover, we identified natural emergence of a BCR with cross-reactivity to SARS-CoV and SARS-CoV-2 in a number of patients. Overall, our results provide important insights for development of rational therapies and vaccines against COVID-19.

Dynamics of B-cell repertoires and emergence of cross-reactive responses in COVID-19 patients with different disease severity.

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