High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients

Wang, Wenjing; Su, Bin; Pang, Lei; Qiao, Li; Feng, Yingmei; Ouyang, Yabo; Guo, Xuesong; Shi, Hang; Wei, Feili; Su, Xiaogang; Ju, Youlun; Jin, Ronghua; Chen, Dexi

doi:10.1038/s41423-020-0447-2

Cited by 119 publications

(130 citation statements)

References 14 publications

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“…The accumulation of exhausted T cells with a reduced functional diversity in peripheral blood of COVID-19 patients with severe symptoms further supports the notion that antigen-specific T cells are instrumental in the control of SARS-CoV-2 infection 12,13 .…”

Section: Sars-cov-2 Is Primarily Transmitted Via Respiratory Dropletssupporting

confidence: 64%

“…Tfh frequencies increase in blood over the course of SARS-CoV-2 infection and are increased in critically ill patients compared to healthy individuals 7,8 .Intriguingly, many patients with severe COVID-19 develop a global T cell lymphopenia, which may reflect massive recruitment to the lungs and other inflamed tissues 2,5,10 . An alternative mechanism that could contribute to the disappearance of circulating T cells may be high levels of activation-induced cell death of lymphocytes in the secondary lymphoid organs 11 .The accumulation of exhausted T cells with a reduced functional diversity in peripheral blood of COVID-19 patients with severe symptoms further supports the notion that antigen-specific T cells are instrumental in the control of SARS-CoV-2 infection 12,13 .We studied the characteristics of SARS-CoV-2-specific adaptive immune responses in COVID-19 individuals with distinct symptoms, ranging from mild and severe to critically ill patients. This type of comparison is essential to understanding the contribution of T and B cell responses to viral clearance and the mechanisms behind immunopathology.…”

mentioning

confidence: 84%

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Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19

Oja

Saris

Ghandour

et al. 2020

Preprint

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 pandemic. Understanding both the immunological processes providing specific immunity and potential immunopathology underlying the pathogenesis of this disease may provide valuable insights for potential therapeutic interventions. Here, we quantified SARS-CoV-2 specific immune responses in patients with different clinical courses. Compared to individuals with a mild clinical presentation, CD4+ T cell responses were qualitatively impaired in critically ill patients.Strikingly, however, in these patients the specific IgG antibody response was remarkably strong. The observed disparate T and B cell responses could be indicative of a deregulated immune response in critically ill COVID-19 patients.The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single-strand RNA virus that has been identified as the causative agent of coronavirus disease 2019 , mainly characterized by respiratory symptoms. This virus appears to be easily transmittable and highly virulent in a sizable fraction of the global population. Consequently, the WHO characterized COVID-19 as a pandemic by March 11 th , 2020. Despite socioeconomic lockdown in about a third of the world, the global number of confirmed SARS-CoV-2 infections surpassed 7 million 1,2 (https://covid19.who.int/). SARS-CoV-2 is primarily transmitted via respiratory droplets and aerosols. The virus infectsairway epithelial cells expressing the surface receptors ACE2 and TMPRSS2. The virus replicates and sheds virus particles, which cause the infected cell to undergo pyroptosis.During this process, damage-associated molecular patterns are released, activating a cascade of pro-inflammatory cytokines and chemokines that attract auxiliary immune cells to the site of infection promoting further inflammation 3 . In severely affected COVID-19 patients this pro-inflammatory cascade appears to be dysregulated, resulting in a life-threatening cytokine storm, which triggers acute respiratory distress syndrome (ARDS) and subsequently other organ dysfunction including, liver, heart, and kidney damage.Clinically, COVID-19 patients can be classified into mild, moderate, severe, and critical cases. Importantly, it has been proposed that the immune response against SARS-CoV-2 is linked to the severity of disease 2,4,5 . Although T cell responses against SARS-CoV-2 proteins have been characterized 6,7 , a comprehensive comparison of the quantity and quality of adaptive immune responses in patients with distinct clinical courses is yet to be performed.Among the cells recruited to the lungs are virus-specific T cells, that have been primed by dendritic cells in the lung draining lymph nodes, and set to kill virus-infected cells, thus preventing further spread and thereby limiting disease progression. Both SARS-CoV-2specific CD8 + and CD4 + T cells and T cells with an activated phenotype have been detected in the blood between 1 and 2 weeks after the onset of ...

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Section: Sars-cov-2 Is Primarily Transmitted Via Respiratory Dropletssupporting

confidence: 64%

mentioning

confidence: 84%

Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19

Oja

Saris

Ghandour

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Immune profiling studies to date have been conducted as single case reports or focused only on moderate, severe or recovered COVID-19 with limited numbers of individuals (15)(16)(17)(18), and have not necessarily reflected the range of comorbidities globally associated with severe COVID-19. Studies of peripheral blood mononuclear cells by mass cytometry or single cell RNA sequencing (scRNAseq) have provided valuable insights into possible immune perturbations in COVID-19 but have not assessed the contributions of granulocytic populations, or, in the case of scRNAseq, defined expression or modulation of cellular proteins (16).…”

Section: Introductionmentioning

confidence: 99%

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

Kuri-Cervantes

Pampena

Meng

et al. 2020

Preprint

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Although critical illness has been associated with SARS-CoV-2-induced hyperinflammation, the immune correlates of severe COVID-19 remain unclear. Here, we comprehensively analyzed peripheral blood immune perturbations in 42 SARS-CoV-2 infected and recovered individuals.We identified broad changes in neutrophils, NK cells, and monocytes during severe COVID-19, suggesting excessive mobilization of innate lineages. We found marked activation within T and B cells, highly oligoclonal B cell populations, profound plasmablast expansion, and SARS-CoV-2specific antibodies in many, but not all, severe COVID-19 cases. Despite this heterogeneity, we found selective clustering of severe COVID-19 cases through unbiased analysis of the aggregated immunological phenotypes. Our findings demonstrate broad immune perturbations spanning both innate and adaptive leukocytes that distinguish dysregulated host responses in severe SARS-CoV-2 infection and warrant therapeutic investigation.One Sentence Summary: Broad immune perturbations in severe COVID-19 surrogates, as well as the medical personnel in charge of patient care.

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“…On the other hand, a high degree of monocyte in ltration has been observed in the lung tissue of COVID-19 patients 22,35 , macrophage in ltration has also been reported recently 47 . The in ltration of monocytes in the lung may be activated by the immune response to form macrophages, which may ultimately promote acute in ammation and cause lung damage through increased M1-polarized macrophages 48 .…”

Section: Comparison Of B-cell Lineage In Ltration In Lung Tissue Betwmentioning

confidence: 66%

“…Related studies showed that CD8 + T cells signi cantly increased bronchoalveolar lavage uid in SARS-CoV-2 infected patients 22 , and CD4 + memory T cells have been reported to respond to viral spike protein after SARS infection 34 . In addition, both CD4 + naïve T cells and CD8 + T were reported to be signi cantly increased by mass cytometry (CyTOF) analysis 35 .…”

Section: Comparison Of T-cell Lineage In Ltration In Lung Tissue Betwmentioning

confidence: 99%

In silico immune infiltration profiling reveals the role of naïve B cells in lung tissues of COVID-19 patients

Chiu

Wang

et al. 2020

Preprint

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COVID-19 caused by SARS-CoV-2 has rapidly spread to more than 160 countries worldwide since 2020. Despite the tremendous efforts and resources spent around the world trying to explore antiviral drugs, there is still no effective clinical treatment for COVID-19. Approximately 15% of COVID-19 cases progress to pneumonia, patients with severe pneumonia may die from acute respiratory distress syndrome (ARDS). In addition, further pulmonary fibrosis from SARS-CoV-2 infection causes ARDS that often leads to irreversible impairment of lung function. If the mechanisms by which SARS-CoV-2 infection primarily cause immune responses or immune cell infiltration can be identified, it is possible to alleviate or prevent severe lung damage by modulating the infiltration and activation of specific immune cells to mitigate excessive immunity response.The extent to which subsets of immune cells are significantly altered in the lung tissue of COVID-19 patients remains unclear. This study applied the CIBERSORT method to comprehensively evaluate the immune infiltration landscape in lung tissues of COVID-19 patients, and further compared with the one from lung tissue of patients with idiopathic pulmonary fibrosis (IPF). We found several immune cell subtypes; particularly naïve B cells are highly infiltrated in COVID-19 group. A comparison of functional gene set analysis revealed that non-differentiated naïve B cells may be the main cause of the overactive humoral immune response. We further compared several specific COVID-19 cases receiving therapies targeting B cells and found that appropriate suppression of naïve B cells might be a new strategy to alleviate severe symptoms of COVID-19.

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High-dimensional immune profiling by mass cytometry revealed immunosuppression and dysfunction of immunity in COVID-19 patients

Cited by 119 publications

References 14 publications

Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19

Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19

Immunologic perturbations in severe COVID-19/SARS-CoV-2 infection

In silico immune infiltration profiling reveals the role of naïve B cells in lung tissues of COVID-19 patients

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