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

ABSTRACT: 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.

SUBMITTER: Wen W

PROVIDER: S-EPMC7197635 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAlthough there are a growing number of studies on evaluating lymphocyte subset counts as prognostic factors for COVID-19 disease severity, the lymphocyte subsets' analyses of both IgM and IgG responders and non-responders during the periods after onset of symptoms, have not been conducted yet. So, this study aimed to evaluate immune cell profiling of COVID-19 patients with and without antibody responses.MethodsIn this cross-sectional study, the levels of peripheral lymphocyte subsets were measured using flow cytometry in 53 patients with positive SARS-CoV-2 RT-PCR, for whom antibody testing of COVID-19 was performed.ResultsThe white blood cell, neutrophil, and lymphocyte counts consistently decreased in the IgM and IgG non-responder group, while the differences in the median value between the two study groups were found to be statistically significant only in terms of neutrophil counts (P = 0.024 for IgM response and p-value = 0.046 for IgG response, respectively). Moreover, the level of neutrophil-to-lymphocyte ratio was observed to be significantly lower in the IgM or IgG non-responder group compared to the IgM or IgG responder group (3.6 ± 3.1 vs. 6.3 ± 4.2; p-value = 0.021). The patients with IgM antibody response had a significantly lower CD20+ lymphocytes (11% versus 15% in the groups without IgM antibody response, p-value = 0.031), The percentages of NK cells and CD4+ T cells significantly increased in the patients with IgG antibody response compared to those without IgG antibody response (13% versus 10%, p-value = 0.028, and 41.5% versus 34%; p-value = 0.03, respectively). Moreover, the patients who produced IgM or IgG antibody had significantly higher percentages of total T lymphocytes (64% versus 54%; p-value = 0.017), CD4+ T cells (41% versus 34%; p-value = 0.038), and NK cells (13% versus 9%, p-value = 0.023) compared to the group with no serological response. No significant difference was observed in the percentage of other lymphocyte subsets, including CD8+ T cells, Treg cells, and CD19+ B cells.ConclusionOur results suggest that the total T cells, CD4+ T cells, and NK cells percentages are linked to serological response. Moreover, our findings suggested that neutrophil absolute counts and neutrophil-to-lymphocyte ratio may be valuable predictors of IgM or IgG antibody response.

Project description:The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5' gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.

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

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