Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing
Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing
复制标题
通过单细胞测序对恢复阶段的 COVID-19 患者进行免疫细胞分析
DOI：
10.1038/s41421-020-0168-9
复制
发表时间：
2020-05-04
期刊：
影响因子：
33.5
通讯作者：
Wang, Hongyang
中科院分区：
文献类型：
--
作者：
Wen, Wen;Su, Wenru;Wang, Hongyang
由SARS-CoV-2引起的COVID-19最近影响了超过120万人，并导致超过6万人死亡。关键的免疫细胞亚群在COVID-19过程中发生变化，其状态仍不清楚。我们试图通过单细胞RNA测序技术全面表征COVID-19恢复期外周血单个核细胞的转录变化。研究发现，在COVID-19的早期恢复期（ERS）患者中，T细胞显著减少，而单核细胞增加。在ERS中，具有高炎症基因表达的经典CD 14 ++单核细胞的比例增加，并且CD 14 ++ IL 1 β+单核细胞的丰度更高。ERS中CD 4 +T细胞和CD 8 +T细胞明显减少，表达高水平的炎性基因。在B细胞中，浆细胞显著增加，而幼稚B细胞减少。鉴定了几种新的B细胞受体（BCR）变化，如IGHV 3 -23和IGHV 3 -7，并确认了先前用于病毒疫苗开发的同种型（IGHV 3 -15、IGHV 3 -30和IGKV 3 -11）。最强的配对频率，IGHV 3 -23-IGHJ 4，表明与SARS-CoV-2特异性相关的单克隆状态，这还没有报道。此外，综合分析预测，IL-1β和M-CSF可能是炎症风暴的新候选靶基因，TNFSF 13、IL-18、IL-2和IL-4可能有利于COVID-19患者的康复。我们的研究提供了ERS中炎症免疫特征的第一个证据，表明COVID-19患者在出院后仍然很脆弱。新BCR信号的鉴定可能会导致用于治疗COVID-19的疫苗和抗体的开发。
COVID-19, caused by SARS-CoV-2, has recently affected over 1,200,000 people and killed more than 60,000. The key immune cell subsets change and their states during the course of COVID-19 remain unclear. We sought to comprehensively characterize the transcriptional changes in peripheral blood mononuclear cells during the recovery stage of COVID-19 by single-cell RNA sequencing technique. It was found that T cells decreased remarkably, whereas monocytes increased in patients in the early recovery stage (ERS) of COVID-19. There was an increased ratio of classical CD14++monocytes with high inflammatory gene expression as well as a greater abundance of CD14++IL1β+monocytes in the ERS. CD4+T cells and CD8+T cells decreased significantly and expressed high levels of inflammatory genes in the ERS. Among the B cells, the plasma cells increased remarkably, whereas the naïve B cells decreased. Several novel B cell-receptor (BCR) changes were identified, such as IGHV3-23 and IGHV3-7, and isotypes (IGHV3-15, IGHV3-30, and IGKV3-11) previously used for virus vaccine development were confirmed. The strongest pairing frequencies, IGHV3-23-IGHJ4, indicated a monoclonal state associated with SARS-CoV-2 specificity, which had not been reported yet. Furthermore, integrated analysis predicted that IL-1β and M-CSF may be novel candidate target genes for inflammatory storm and that TNFSF13, IL-18, IL-2, and IL-4 may be beneficial for the recovery of COVID-19 patients. Our study provides the first evidence of an inflammatory immune signature in the ERS, suggesting COVID-19 patients are still vulnerable after hospital discharge. Identification of novel BCR signaling may lead to the development of vaccines and antibodies for the treatment of COVID-19.