Hyperoxia and modulation of pulmonary vascular and immune responses in COVID-19 DOI Open Access
Dusan Hanidziar, Simon C. Robson

AJP Lung Cellular and Molecular Physiology, Journal Year: 2020, Volume and Issue: 320(1), P. L12 - L16

Published: Oct. 14, 2020

Oxygen is the most commonly used therapy in hospitalized patients with COVID-19. In those who develop worsening pneumonia and acute respiratory distress syndrome (ARDS), high concentrations of oxygen may need to be administered for prolonged time periods, often together mechanical ventilation. Hyperoxia, although lifesaving essential maintaining adequate oxygenation short term, have adverse long-term consequences upon lung parenchymal structure function. How hyperoxia per se impacts disease COVID-19 has remained largely unexplored. Numbers experimental studies previously established that associated deleterious outcomes inclusive perturbations immunologic responses, abnormal metabolic function, alterations hemodynamics alveolar barrier Such changes ultimately progress into clinically evident injury remodeling result fibrosis when exposure prolonged. Given significant severe unavoidable preserve life, these sequelae hyperoxia, superimposed on cytopathic effects SARS-CoV-2 virus, well impact pathogenesis COVID-19-induced ARDS.

Language: Английский

COVID-19 immune features revealed by a large-scale single-cell transcriptome atlas DOI Creative Commons
Xianwen Ren, Wen Wen, Xiaoying Fan

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(7), P. 1895 - 1913.e19

Published: Feb. 5, 2021

Language: Английский

Citations

724
Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19 DOI Open Access
Pierre‐François Dequin, Nicholas Heming, Ferhat Meziani

et al.

JAMA, Journal Year: 2020, Volume and Issue: 324(13), P. 1298 - 1298

Published: Sept. 2, 2020

Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option.

Language: Английский

Citations

453
A blood atlas of COVID-19 defines hallmarks of disease severity and specificity DOI Creative Commons
David Ahern, Zhichao Ai, Mark Ainsworth

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 916 - 938.e58

Published: Jan. 21, 2022

Treatment of severe COVID-19 is currently limited by clinical heterogeneity and incomplete description specific immune biomarkers. We present here a comprehensive multi-omic blood atlas for patients with varying severity in an integrated comparison influenza sepsis versus healthy volunteers. identify signatures correlates host response. Hallmarks disease involved cells, their inflammatory mediators networks, including progenitor cells myeloid lymphocyte subsets, features the repertoire, acute phase response, metabolism, coagulation. Persisting activation involving AP-1/p38MAPK was feature COVID-19. The plasma proteome enabled sub-phenotyping into patient clusters, predictive outcome. Systems-based integrative analyses tensor matrix decomposition all modalities revealed groupings linked specificity compared to sepsis. Our approach will support future drug development, trial design, personalized medicine approaches

Language: Английский

Citations

266
The differential immune responses to COVID-19 in peripheral and lung revealed by single-cell RNA sequencing DOI Creative Commons
Gang Xu, Furong Qi, Hanjie Li

et al.

Cell Discovery, Journal Year: 2020, Volume and Issue: 6(1)

Published: Oct. 20, 2020

Abstract Understanding the mechanism that leads to immune dysfunction in severe coronavirus disease 2019 (COVID-19) is crucial for development of effective treatment. Here, using single-cell RNA sequencing, we characterized peripheral blood mononuclear cells (PBMCs) from uninfected controls and COVID-19 patients paired broncho-alveolar lavage fluid (BALF). We found a close association decreased dendritic (DCs) increased monocytes resembling myeloid-derived suppressor (MDSCs), which correlated with lymphopenia inflammation patients. Those MDSC-like were immune-paralyzed. In contrast, monocyte-macrophages BALFs produced massive amounts cytokines chemokines, but secreted little interferons. The frequencies T NK significantly patients, especially innate-like various CD8 + cell subsets, compared healthy controls. proportions activated CD4 subsets among compartment, including Th1, Th2, Th17-like more clonally expanded Patients’ showed no sign exhaustion or augmented death, whereas higher levels IFNG , TNF CCL4 CCL5 etc. Paired TCR tracking indicated abundant recruitment patients’ lung. Together, this study comprehensively depicts how landscape perturbed COVID-19.

Language: Английский

Citations

222
Outcome of SARS-CoV-2 infection is linked to MAIT cell activation and cytotoxicity DOI Creative Commons
Héloïse Flament, Matthieu Rouland,

Lucie Beaudoin

et al.

Nature Immunology, Journal Year: 2021, Volume and Issue: 22(3), P. 322 - 335

Published: Feb. 2, 2021

Immune system dysfunction is paramount in coronavirus disease 2019 (COVID-19) severity and fatality rate. Mucosal-associated invariant T (MAIT) cells are innate-like involved mucosal immunity protection against viral infections. Here, we studied the immune cell landscape, with emphasis on MAIT cells, cohorts totaling 208 patients various stages of disease. frequency strongly reduced blood. They display a strong activated cytotoxic phenotype that more pronounced lungs. Blood alterations positively correlate activation other innate proinflammatory cytokines, notably interleukin (IL)-18, mortality severe acute respiratory syndrome 2 infection. We also identified monocyte/macrophage interferon (IFN)-α–IL-18 cytokine shift ability infected macrophages to induce cytotoxicity an MR1-dependent manner. Together, our results suggest altered functions due IFN-α–IL-18 imbalance contribute severity, their therapeutic manipulation may prevent deleterious inflammation COVID-19 aggravation. Severe characterized by hyperinflammation, there need for accurate predictive biomarkers progression. Lehuen et al. demonstrate show dramatic loss those do remain highly state.

Language: Английский

Citations

190
MAIT cell activation and dynamics associated with COVID-19 disease severity DOI Creative Commons
Tiphaine Parrot, Jean‐Baptiste Gorin, Andrea Ponzetta

et al.

Science Immunology, Journal Year: 2020, Volume and Issue: 5(51)

Published: Sept. 18, 2020

MAIT cell activation and decline in blood are associated with COVID-19 severity, features that dynamically recover convalescence.

Language: Английский

Citations

186
Mucosal immune responses to infection and vaccination in the respiratory tract DOI Creative Commons
Robert C. Mettelman, E. Kaitlynn Allen, Paul G. Thomas

et al.

Immunity, Journal Year: 2022, Volume and Issue: 55(5), P. 749 - 780

Published: May 1, 2022

Language: Английский

Citations

156
The impact of pre-existing cross-reactive immunity on SARS-CoV-2 infection and vaccine responses DOI Open Access
Sam M. Murray, M. Azim Ansari, John Frater

et al.

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 23(5), P. 304 - 316

Published: Dec. 20, 2022

Language: Английский

Citations

122
γδ T cells: origin and fate, subsets, diseases and immunotherapy DOI Creative Commons
Yi Hu,

Qinglin Hu,

Yongsheng Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 22, 2023

The intricacy of diseases, shaped by intrinsic processes like immune system exhaustion and hyperactivation, highlights the potential renormalization as a promising strategy in disease treatment. In recent years, our primary focus has centered on γδ T cell-based immunotherapy, particularly pioneering use allogeneic Vδ2

Language: Английский

Citations

113
T cell immunity to SARS-CoV-2 following natural infection and vaccination DOI Open Access
Anthony DiPiazza, Barney S. Graham, Tracy J. Ruckwardt

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2020, Volume and Issue: 538, P. 211 - 217

Published: Oct. 23, 2020

Language: Английский

Citations

115