Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19

@article{Sinha2021DexamethasoneMI,
  title={Dexamethasone modulates immature neutrophils and interferon programming in severe COVID-19},
  author={Sarthak Sinha and Nicole L Rosin and Rohit Arora and Elodie Labit and Arzina Jaffer and Leslie Cao and Raquel Farias and Angela P Nguyen and Luiz G. N. de Almeida and Antoine Dufour and Amy Bromley and Braedon McDonald and Mark R. Gillrie and Marvin J. Fritzler and Bryan G. Yipp and Jeff Biernaskie},
  journal={Nature Medicine},
  year={2021},
  volume={28},
  pages={201 - 211}
}
Although critical for host defense, innate immune cells are also pathologic drivers of acute respiratory distress syndrome (ARDS). Innate immune dynamics during Coronavirus Disease 2019 (COVID-19) ARDS, compared to ARDS from other respiratory pathogens, is unclear. Moreover, mechanisms underlying the beneficial effects of dexamethasone during severe COVID-19 remain elusive. Using single-cell RNA sequencing and plasma proteomics, we discovered that, compared to bacterial ARDS, COVID-19 was… 

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References

SHOWING 1-10 OF 53 REFERENCES

The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing

TLDR
This study comprehensively depicts how the immune cell landscape is perturbed in severe COVID-19 and indicates abundant recruitment of peripheral T cells to the severe patients’ lung.

Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome

TLDR
NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.

Discriminating mild from critical COVID-19 by innate and adaptive immune single-cell profiling of bronchoalveolar lavages

TLDR
Single-cell profiling to bronchoalveolar lavages from 44 patients with mild or critical CO VID-19 versus non-COVID-19 pneumonia as control represents a major resource for understanding the lung-localised immunity and inflammation landscape during COVID- 19.

Multi-omic profiling reveals widespread dysregulation of innate immunity and hematopoiesis in COVID-19

TLDR
The authors' transcriptomic, epigenomic, and proteomic analyses reveal widespread dysfunction of peripheral innate immunity in severe and fatal COVID-19, with the most profound disturbances including a prominent neutrophil hyperactivation signature and monocytes with anti-inflammatory features.

Single-Cell Transcriptome Analysis Highlights a Role for Neutrophils and Inflammatory Macrophages in the Pathogenesis of Severe COVID-19

TLDR
The presence of neutrophils and macrophage cluster-1 is revealed as the main immune cell subsets associated with severe COVID-19 and their inflammatory and chemotactic gene signatures are identified, also partially reflected systemically in the circulation, for possible diagnostic and therapeutic interventions.

Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19

TLDR
It is proposed that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.

Global Absence and Targeting of Protective Immune States in Severe COVID-19.

TLDR
Examination of the serum from severe patients demonstrates that they uniquely produce antibodies with multiple patterns of specificity against interferon-stimulated cells and that those antibodies functionally block the production of the mild disease-associated ISG-expressing cells.

A single-cell atlas of the peripheral immune response in patients with severe COVID-19

TLDR
Single-cell transcriptomic analysis identifies changes in peripheral immune cells in seven hospitalized patients with COVID-19, including HLA class II downregulation, a heterogeneous interferon-stimulated gene signature and low pro-inflammatory cytokine gene expression in monocytes and lymphocytes.
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