Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients

Zhu, Linnan; Yang, Peng; Zhao, Yang; Zhuang, Zhenkun; Wang, Zhifeng; Song, Rui; Zhang, Jie; Liu, Chuanyu; Gao, Qianqian; Xu, Qumiao; Wei, Xiaoyü; Sun, Haixi; Ye, Beiwei; Wu, Yanan; Zhang, Ning; Lei, Guanglin; Yu, Lingxiang; Jin, Yan; Diao, Guanghao; Meng, Fanping; Bai, Chunmei; Mao, Panyong; Yu, Yeya; Wang, Mingyue; Yuan, Yue; Deng, Qiuting; Li, Ziyi; Huang, Yunting; Hu, Guohai; Liu, Yang; Wang, Xiaoqian; Xu, Ziqian; Li, Peipei; Bi, Yang; Shi, Yi; Zhang, Shaogeng; Chen, Zhihai; Wang, Jian; Xu, Xun; Wu, Guizhen; Wang, Fusheng; Gao, George F.; Liu, Longqi; Liu, William J.

doi:10.1016/j.immuni.2020.07.009

Cited by 325 publications

(362 citation statements)

References 44 publications

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“…While we only have samples from the early stage in a severe patient and cannot assess the change in late stage, another study has shown that the cytokines related to IFN-I, such as IFNa, did not decrease in severe condition over time (Lucas et al, 2020). Second, we found different proportions of immune subsets in different conditions that consistent with recent studies (Lee et al, 2020;Liao et al, 2020;Lucas et al, 2020;Wilk et al, 2020;Zhu et al, 2020), including the increased plasma B cells and decreased T subsets in severe conditions. Higher proportions of T subsets were marked in moderate condition, and TCR analysis showed increased clonal expansion of T cells compared to other conditions .…”

Section: Discussionsupporting

confidence: 92%

“…However, severe patients have much higher expression of these genes (Figure 5g), indicating more robust activation of IFN-I signaling pathway response and a pro-inflammatory state. Notably, we also found increased expression of STAT1 in severe patients (Figure 5g), which was consistent with a previous study (Zhu et al, 2020).…”

Section: Features Of B Cells and Expansion And Specific Rearrangementsupporting

confidence: 93%

“…Elevated pro-inflammatory cytokines (e.g., and inflammatory monocytes and neutrophils and a sharp decrease in lymphocytes have also been reported in severe patients (Chen et al, 2020a;Chen et al, 2020b;Giamarellos-Bourboulis et al, 2020;Huang et al, 2020;Jose and Manuel, 2020;Lucas et al, 2020;Mathew et al, 2020;Skarica et al, 2011;Zhou et al, 2020). Further, single-cell RNA sequencing (scRNA-seq) studies of peripheral blood mononuclear cells (PBMCs) or bronchoalveolar lavages have reported the immunological profiles to SARS-CoV-2 in severe and moderate patients (Lee et al, 2020;Liao et al, 2020;Mathew et al, 2020;Wilk et al, 2020;Zhu et al, 2020), suggesting moderate disease was associated with more protective T cell-dependent response, with exacerbated systemic inflammation and less effect T cells in severe disease. Longitudinal immune responses of moderate and severe COVID-19 patients have been analyzed by flow cytometry (Lucas et al, 2020), while unbiased longitudinal single-cell transcriptome profiling is still missing.…”

Section: Introductionmentioning

confidence: 99%

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Longitudinal single-cell immune profiling revealed distinct innate immune response in asymptomatic COVID-19 patients

Zhao

You

Wang

et al. 2020

Preprint

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SUMMARYRecent studies have characterized the single-cell immune landscape of host immune response of coronavirus disease 2019 (COVID-19), specifically focus on the severe condition. However, the immune response in mild or even asymptomatic patients remains unclear. Here, we performed longitudinal single-cell transcriptome sequencing and T cell/B cell receptor sequencing on 3 healthy donors and 10 COVID-19 patients with asymptomatic, moderate, and severe conditions. We found asymptomatic patients displayed distinct innate immune responses, including increased CD56briCD16− NK subset, which was nearly missing in severe condition and enrichment of a new Th2-like cell type/state expressing a ciliated cell marker. Unlike that in moderate condition, asymptomatic patients lacked clonal expansion of effector CD8+ T cells but had a robust effector CD4+ T cell clonal expansion, coincide with previously detected SARS-CoV-2-reactive CD4+ T cells in unexposed individuals. Moreover, NK and effector T cells in asymptomatic patients have upregulated cytokine related genes, such as IFNG and XCL2. Our data suggest early innate immune response and type I immunity may contribute to the asymptomatic phenotype in COVID-19 disease, which could in turn deepen our understanding of severe COVID-19 and guide early prediction and therapeutics.

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Section: Discussionsupporting

confidence: 92%

Section: Features Of B Cells and Expansion And Specific Rearrangementsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Longitudinal single-cell immune profiling revealed distinct innate immune response in asymptomatic COVID-19 patients

Zhao

You

Wang

et al. 2020

Preprint

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“…Possibly in relation to the overt subset-selective T apoptosis reported for COVID-19 24 , we found signi cantly increased and sustained levels of plasma markers associated with apoptosis. Among these, we observed consistent increases in the levels of CASP8, TNFSF14 and TGFB1, three biomarkers established to be related to in ammation combined with apoptosis.…”

Section: Sustained Markers Related To Apoptosis and In Ammationsupporting

confidence: 56%

Longitudinal proteomic profiling reveals increased early inflammation and sustained apoptosis proteins in severe COVID-19

Haljasmägi

Salumets

Rumm

et al. 2020

Preprint

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SARS-CoV-2 infection risks developing into life-threatening COVID-19 disease. Whereas age, hypertension, and chronic inflammatory conditions are risk factors, underlying host factors and markers for disease severity, e.g. requiring intensive care unit (ICU) treatment, remain poorly defined. To this end, we longitudinally profiled blood inflammation markers, antibodies, and 101 plasma proteins of hospitalized COVID-19 patients who did or did not require (ICU admission. Whereas essentially all patients displayed SARS-CoV-2-specific antibodies and virus-neutralization capacity within 12-15 days, a rapid, mostly transient upregulation of selective inflammatory markers including IL-6, CXCL10, CXCL11, IFNg, IL-10, and monocyte-attracting CCL2, CCL7 and CCL8, was particularly evident in ICU patients. In addition, there was consistent and sustained upregulation of apoptosis-associated proteins CASP8, TNFSF14, HGF, and TGFB1, with HGF discriminating between ICU and non-ICU cohorts. Thus, COVID-19 is associated with a selective inflammatory milieu within which the apoptotic pathway is a cardinal feature with potential to aid risk-based patient stratification.

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“…Interestingly, we found the death and apoptosis process were mainly shown in the biological process panel. A recent report showed that XAF1, TNNF, and FAS induce T cell apoptosis in COVID-19 patients (16). The previous report showed cilium abnormalities in bronchus are associated with COVID-19 (17).…”

Section: Discussionmentioning

confidence: 95%

Identification of potential key genes for SARS-CoV-2 infected human bronchial organoids based on bioinformatics analysis

Yuan

2020

Preprint

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There is an urgent need to understand the pathogenesis of the severe acute respiratory syndrome coronavirus clade 2 (SARS-CoV-2) that leads to COVID-19 and respiratory failure. Our study is to discover differentially expressed genes (DEGs) and biological signaling pathways by using a bioinformatics approach to elucidate their potential pathogenesis. The gene expression profiles of the GSE150819 datasets were originally produced using an Illumina NextSeq 500 (Homo sapiens). KEGG (Kyoto Encyclopedia of Genes and Genomes) and GO (Gene Ontology) were utilized to identify functional categories and significant pathways. KEGG and GO results suggested that the Cytokine-cytokine receptor interaction, P53 signaling pathway, and Apoptosis are the main signaling pathways in SARS-CoV-2 infected human bronchial organoids (hBOs). Furthermore, NFKBIA, C3, and CCL20 may be key genes in SARS-CoV-2 infected hBOs. Therefore, our study provides further insights into the therapy of COVID-19.

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Single-Cell Sequencing of Peripheral Mononuclear Cells Reveals Distinct Immune Response Landscapes of COVID-19 and Influenza Patients

Cited by 325 publications

References 44 publications

Longitudinal single-cell immune profiling revealed distinct innate immune response in asymptomatic COVID-19 patients

Longitudinal single-cell immune profiling revealed distinct innate immune response in asymptomatic COVID-19 patients

Longitudinal proteomic profiling reveals increased early inflammation and sustained apoptosis proteins in severe COVID-19

Identification of potential key genes for SARS-CoV-2 infected human bronchial organoids based on bioinformatics analysis

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