Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing

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. Researchers at the National Center for Liver Cancer, Shanghai 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.

Study design and analysis of single immune cell profiling in COVID-19 patients

figure1

a Schematics of the experimental design for single-cell RNA (sc-RNA) sequencing. Peripheral blood mononuclear cells (PBMCs) were collected from COVID-19 patients and healthy controls (HCs) and then processed via sc-RNA, sc-BCR, and sc-TCR sequencing using the 10x-Based Genomics platform. b The heatmaps show differentially expressed genes (DEGs) upregulated in myeloid cells, NK and T cells, B cells, and other clusters of PBMCs. c t-distributed stochastic neighbor embedding (t-SNE) plot showing myeloid cells (red), NK and T cells (blue), B cells (green), and other clusters (gray) of PBMCs identified using integrated and classification analysis. d t-SNE projection of canonical markers, including CD14, CD1C, and FCGR3A for myeloid cells; CD3E, CD4, CD8A, and NCAM1 for NK and T cells; and CD19 for B cells as indicated in the legend.

This 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.

Wen W, Su W, Tang H, Le W, Zhang X, Zheng Y, Liu X, Xie L, Li J, Ye J, Dong L, Cui X, Miao Y, Wang D, Dong J, Xiao C, Chen W, Wang H. (2020) Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing. Cell Discov 6:31. [article]

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