Dysregulated adaptive immune response contributes to severe COVID-19

Yu, Kuai; He, Jingjing; Wu, Yongjian; Xie, Baosong; Liu, Xuefei; Wei, Bo; Zhou, Haibo; Lin, Bingliang; Zuo, Zhixiang; Wen, Wen; Xu, Wenxiong; Zou, Bin; Wei, Lai; Huang, Xi; Zhou, Penghui

doi:10.1038/s41422-020-0391-9

Cited by 73 publications

(69 citation statements)

References 12 publications

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“…Analysis of transcriptional responses in peripheral blood from patients with SARS-CoV-2 infection reveals that SARS-CoV-2 triggers inflammatory and humoral immune response pathways in ways that are distinct from those seen in other common respiratory infections. These SARS-CoV-2 specific signals further support the growing body of evidence that dysregulated immunity likely contributes to early viral shedding 8 and progression to severe disease 9 , 37 , 38 . The marked heterogeneity seen in many inflammatory pathways underscores the potential importance of defining the pathophysiology of infection at the individual level, especially when considering immunomodulatory therapy 31 .…”

Section: Discussionsupporting

confidence: 68%

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery

et al. 2021

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SARS-CoV-2 infection has been shown to trigger a wide spectrum of immune responses and clinical manifestations in human hosts. Here, we sought to elucidate novel aspects of the host response to SARS-CoV-2 infection through RNA sequencing of peripheral blood samples from 46 subjects with COVID-19 and directly comparing them to subjects with seasonal coronavirus, influenza, bacterial pneumonia, and healthy controls. Early SARS-CoV-2 infection triggers a powerful transcriptomic response in peripheral blood with conserved components that are heavily interferon-driven but also marked by indicators of early B-cell activation and antibody production. Interferon responses during SARS-CoV-2 infection demonstrate unique patterns of dysregulated expression compared to other infectious and healthy states. Heterogeneous activation of coagulation and fibrinolytic pathways are present in early COVID-19, as are IL1 and JAK/STAT signaling pathways, which persist into late disease. Classifiers based on differentially expressed genes accurately distinguished SARS-CoV-2 infection from other acute illnesses (auROC 0.95 [95% CI 0.92–0.98]). The transcriptome in peripheral blood reveals both diverse and conserved components of the immune response in COVID-19 and provides for potential biomarker-based approaches to diagnosis.

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Section: Discussionsupporting

confidence: 68%

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery

et al. 2021

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“…While most previous studies did not discriminate whether convalescent individuals recovered from mild/moderate or severe symptoms, we divided the convalescent group into two subgroups, 54 recovered from mild/moderate symptoms and 38 recovered from severe symptoms, to investigate the effects of disease severity on the immune status of recovered individuals. This cohort covered a wide age range (from 6 to 92 years old), with the mild/moderate and severe groups having significant age differences (Figure S1A), consistent with the epidemiological observations that aged patients are prone to severe symptoms (Guo et al, 2020a; Hadjadj et al, 2020; Silvin et al, 2020b; Wilk et al, 2020; Yu et al, 2020). Additionally, no significant difference was noted in the sex composition between the mild/moderate and severe groups (Figure S1B).…”

Section: Resultssupporting

confidence: 84%

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients

Ren¹,

Wen²,

Fan³

et al. 2020

Preprint

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Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic up-regulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19.

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“…The immunophenotyping analysis revealed a strong effect of Tα1 in T-cell subsets. In a recent study, researchers demonstrated that Tα1 administration could increase lymphocytes count, and this could be a potential approach to protect effector T cells during COVID-19 [ 44 ]. Thymosin alpha 1 significantly decreases the expression of the intracellular IL-6 and the activation markers CD38 and HLA-DR in CD4 + T cells in both patients with COVID-19 and HDs.…”

Section: Discussionmentioning

confidence: 99%

Thymosin Alpha 1 Mitigates Cytokine Storm in Blood Cells From Coronavirus Disease 2019 Patients

Matteucci

Minutolo

Balestrieri

et al. 2020

Open Forum Infectious Diseases

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Background Coronavirus disease 2019 (COVID-19) is characterized by immune-mediated lung injury and complex alterations of the immune system, such as lymphopenia and cytokine storm, that have been associated with adverse outcomes underlining a fundamental role of host response in severe acute respiratory syndrome coronavirus 2 infection and the pathogenesis of the disease. Thymosin alpha 1 (Tα1) is one of the molecules used in the management of COVID-19, because it is known to restore the homeostasis of the immune system during infections and cancer. Methods In this study, we captured the interconnected biological processes regulated by Tα1 in CD8+ T cells under inflammatory conditions. Results Genes associated with cytokine signaling and production were upregulated in blood cells from patients with COVID-19, and the ex vivo treatment with Tα1-mitigated cytokine expression, and inhibited lymphocyte activation in a CD8+ T-cell subset specifically. Conclusion These data suggest the potential role of Tα1 in modulating the immune response homeostasis and the cytokine storm in vivo.

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Dysregulated adaptive immune response contributes to severe COVID-19

Cited by 73 publications

References 12 publications

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery

Dysregulated transcriptional responses to SARS-CoV-2 in the periphery

Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients

Thymosin Alpha 1 Mitigates Cytokine Storm in Blood Cells From Coronavirus Disease 2019 Patients

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