Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection

Żmijewski, Jaroslaw W.; Pittet, Jean François

doi:10.1213/ane.0000000000005140

Cited by 7 publications

(8 citation statements)

References 36 publications

(31 reference statements)

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“…We analyzed individual rDEGs in each of our five most abundant cell types: M1 MoMa, M2 MoMa, CD4+ T cells, NK cells, and CD8+ memory T cells ( Fig 3 ). This analysis confirmed previous reports of downregulation of HLA genes [ 36 , 73 ] such as HLA-DRA and HLA-DRB5 in COVID-19 patients, with severe patients showing the most downregulation. We also saw upregulation of interferon related genes including MX1 and IFIT1-3.…”

Section: Resultssupporting

confidence: 91%

Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single-cell analysis

et al. 2022

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Hyperactive and damaging inflammation is a hallmark of severe rather than mild Coronavirus disease 2019 (COVID-19). To uncover key inflammatory differentiators between severe and mild COVID-19, we applied an unbiased single-cell transcriptomic analysis. We integrated two single-cell RNA-seq datasets with COVID-19 patient samples, one that sequenced bronchoalveolar lavage (BAL) cells and one that sequenced peripheral blood mononuclear cells (PBMCs). The combined cell population was then analyzed with a focus on genes associated with disease severity. The immunomodulatory long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 were highly differentially expressed between mild and severe patients in multiple cell types. Within those same cell types, the concurrent detection of other severity-associated genes involved in cellular stress response and apoptosis regulation suggests that the pro-inflammatory functions of these lncRNAs may foster cell stress and damage. Thus, NEAT1 and MALAT1 are potential components of immune dysregulation in COVID-19 that may provide targets for severity related diagnostic measures or therapy.

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Section: Resultssupporting

confidence: 91%

Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single-cell analysis

et al. 2022

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“…We analyzed individual rDEGs in each of our five most abundant cell types: M1 MoMa, M2 MoMa, CD4+ T cells, NK cells, and CD8+ memory T cells ( Figure 3 ). This analysis confirmed previous reports of downregulation of HLA genes(20,58) such as HLA-DRA and HLA-DRB5 in COVID-19 patients, with severe patients showing the most downregulation. We also saw upregulation of interferon related genes including MX1, and IFIT1-3.…”

Section: Resultssupporting

confidence: 91%

Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single cell analysis

Kai

Wang

Vagts

et al. 2021

Preprint

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Hyperactive and damaging inflammation is a hallmark of severe rather than mild COVID-19 syndrome. To uncover key inflammatory differentiators between severe and mild COVID-19 disease, we applied an unbiased single-cell transcriptomic analysis. We integrated a bronchoalveolar lavage (BAL) dataset with a peripheral blood mononuclear cell dataset (PBMC) and analyzed the combined cell population, focusing on genes associated with disease severity. Distinct cell populations were detected in both BAL and PBMC where the immunomodulatory long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 were highly differentially expressed between mild and severe patients. The detection of other severity associated genes involved in cellular stress response and apoptosis regulation suggests that the pro-inflammatory functions of these lncRNAs may foster cell stress and damage. The lncRNAs NEAT1 and MALAT1 are potential components of immune dysregulation in COVID-19 that may provide targets for severity related diagnostic measures or therapy.

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“…Decreased HLA-DR and increased PD-L1 expression has been documented in COVID-19 monocytes (94). These findings suggest exhaustion of these cells and probably impaired antigen presentation to naive T cells (113). DCs in COVID-19 patients are reduced, with impaired maturation and function, suggesting also impaired antigen presentation and T cell activation (114).…”

Section: Deregulated Innate Immunitymentioning

confidence: 95%

COVID-19 Immunobiology: Lessons Learned, New Questions Arise

et al. 2021

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There is strong evidence that COVID-19 pathophysiology is mainly driven by a spatiotemporal immune deregulation. Both its phenotypic heterogeneity, spanning from asymptomatic to severe disease/death, and its associated mortality, are dictated by and linked to maladaptive innate and adaptive immune responses against SARS-CoV-2, the etiologic factor of the disease. Deregulated interferon and cytokine responses, with the contribution of immune and cellular stress-response mediators (like cellular senescence or uncontrolled inflammatory cell death), result in innate and adaptive immune system malfunction, endothelial activation and inflammation (endothelitis), as well as immunothrombosis (with enhanced platelet activation, NET production/release and complement hyper-activation). All these factors play key roles in the development of severe COVID-19. Interestingly, another consequence of this immune deregulation, is the production of autoantibodies and the subsequent development of autoimmune phenomena observed in some COVID-19 patients with severe disease. These new aspects of the disease that are now emerging (like autoimmunity and cellular senescence), could offer us new opportunities in the field of disease prevention and treatment. Simultaneously, lessons already learned from the immunobiology of COVID-19 could offer new insights, not only for this disease, but also for a variety of chronic inflammatory responses observed in autoimmune and (auto)inflammatory diseases.

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Human Leukocyte Antigen-DR Deficiency and Immunosuppression-Related End-Organ Failure in SARS-CoV2 Infection

Cited by 7 publications

References 36 publications

Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single-cell analysis

Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single-cell analysis

Long non-coding RNAs (lncRNAs) NEAT1 and MALAT1 are differentially expressed in severe COVID-19 patients: An integrated single cell analysis

COVID-19 Immunobiology: Lessons Learned, New Questions Arise

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