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.

中文翻译：

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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。


由 SARS-CoV-2 引起的 COVID-19 最近已影响超过 1,200,000 人，并导致 60,000 多人死亡。 COVID-19 期间关键免疫细胞亚群发生变化及其状态仍不清楚。我们试图通过单细胞 RNA 测序技术全面表征 COVID-19 恢复阶段外周血单核细胞的转录变化。研究发现，在COVID-19恢复早期（ERS）患者中，T细胞显着减少，而单核细胞增加。 ERS 中具有高炎症基因表达的经典 CD14++ 单核细胞比例增加，并且 CD14++IL1β+ 单核细胞丰度更高。 ERS 中 CD4+ T 细胞和 CD8+ T 细胞显着减少，并表达高水平的炎症基因。 B细胞中，浆细胞显着增加，而幼稚B细胞减少。鉴定了几种新的 B 细胞受体 (BCR) 变化，例如 IGHV3-23 和 IGHV3-7，并确认了先前用于病毒疫苗开发的同种型（IGHV3-15、IGHV3-30 和 IGKV3-11）。最强的配对频率 IGHV3-23-IGHJ4 表明与 SARS-CoV-2 特异性相关的单克隆状态，但尚未有报道。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，TNFSF13、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 患者出院后仍然很脆弱。新型 BCR 信号传导的鉴定可能有助于开发治疗 COVID-19 的疫苗和抗体。