Characteristics and comparative clinical outcomes of prisoner versus non-prisoner populations hospitalized with COVID-19

Prisons in the United States have become a hotbed for spreading COVID-19 among incarcerated individuals. COVID-19 cases among prisoners are on the rise, with more than 143,000 confirmed cases to date. However, there is paucity of data addressing clinical outcomes and mortality in prisoners hospitalized with COVID-19. An observational study of all patients hospitalized with COVID-19 between March 10 and May 10, 2020 at two Henry Ford Health System hospitals in Michigan. Clinical outcomes were compared amongst hospitalized prisoners and non-prisoner patients. The primary outcomes were intubation rates, in-hospital mortality, and 30-day mortality. Multivariable logistic regression and Cox-regression models were used to investigate primary outcomes. Of the 706 hospitalized COVID-19 patients (mean age 66.7 ± 16.1 years, 57% males, and 44% black), 108 were prisoners and 598 were non-prisoners. Compared to non-prisoners, prisoners were more likely to present with fever, tachypnea, hypoxemia, and markedly elevated inflammatory markers. Prisoners were more commonly admitted to the intensive care unit (ICU) (26.9% vs. 18.7%), required vasopressors (24.1% vs. 9.9%), and intubated (25.0% vs. 15.2%). Prisoners had higher unadjusted inpatient mortality (29.6% vs. 20.1%) and 30-day mortality (34.3% vs. 24.6%). In the adjusted models, prisoner status was associated with higher in-hospital death (odds ratio, 2.32; 95% confidence interval (CI), 1.33 to 4.05) and 30-day mortality (hazard ratio, 2.00; 95% CI, 1.33 to 3.00). In this cohort of hospitalized COVID-19 patients, prisoner status was associated with more severe clinical presentation, higher rates of ICU admissions, vasopressors requirement, intubation, in-hospital mortality, and 30-day mortality

A microRNA profile of human CD8(+) regulatory T cells and characterization of the effects of microRNAs on Treg cell-associated genes.

Recently, regulatory T (Treg) cells have gained interest in the fields of immunopathology, transplantation and oncoimmunology. Here, we investigated the microRNA expression profile of human natural CD8(+)CD25(+) Treg cells and the impact of microRNAs on molecules associated with immune regulation. We purified human natural CD8(+) Treg cells and assessed the expression of FOXP3 and CTLA-4 by flow cytometry. We have also tested the ex vivo suppressive capacity of these cells in mixed leukocyte reactions. Using TaqMan low-density arrays and microRNA qPCR for validation, we could identify a microRNA 'signature' for CD8(+)CD25(+)FOXP3(+)CTLA-4(+) natural Treg cells. We used the 'TargetScan' and 'miRBase' bioinformatics programs to identify potential target sites for these microRNAs in the 3'-UTR of important Treg cell-associated genes. The human CD8(+)CD25(+) natural Treg cell microRNA signature includes 10 differentially expressed microRNAs. We demonstrated an impact of this signature on Treg cell biology by showing specific regulation of FOXP3, CTLA-4 and GARP gene expression by microRNA using site-directed mutagenesis and a dual-luciferase reporter assay. Furthermore, we used microRNA transduction experiments to demonstrate that these microRNAs impacted their target genes in human primary Treg cells ex vivo. We are examining the biological relevance of this 'signature' by studying its impact on other important Treg cell-associated genes. These efforts could result in a better understanding of the regulation of Treg cell function and might reveal new targets for immunotherapy in immune disorders and cancer

Evaluation of an anti-inflammatory dendrimer to topically treat psoriasis

International audiencePsoriasis is an auto-immune disease resulting from a chronic and exaggerated inflammation of the skin and hyperproliferation of keratinocytes. Conventional topical treatments for this disease, such as anti-inflammatory drugs, present low efficiency, and systemic administration of synthetic drugs or biologic immunomodulators can present severe side effects and/or are highly expensive. So, there is an unmet need to develop new drugs that could provide sustainable therapeutic effects. In this study, we evaluated the potential efficacy of anti-inflammatory dendrimers for the topical treatment of psoriasis. Dendrimers are hyperbranched and perfectly defined macromolecules of nanometer size, constituted of branches grafted on a central core. IMD-006, a phosphorus-based dendrimer capped with azabisphosphonate groups, has strong immuno-modulatory effects towards different immune cell types. Wetested the effects of IMD-006 in two psoriasis models: the imiquimod- induced murine model and a reconstructed human epidermis (RHE) model, in which cocktails of pro-inflammatory cytokines are used to induce psoriasis-associated changes. IMD-006 presented dose-dependent therapeutic efficacies, significantly reducing lesions and histopathological changes associated with psoriasis. Moreover, we show that IMD-006 is rapidly taken up by kerati-nocytes in 2D culture, decreasing their proliferation and increasing their differentiation. In keratinocytes in 2D culture, IMD-006 associated with mitochondria, increased mitochondrial ROS production and ultimately lysosomal degradation of these organelles. Therefore, the anti-psoriatic effect of dendrimers is, at least in part, the result of a direct effect on keratinocytes. Our results demonstrate that anti-inflammatory dendrimers are good candidates forthe topical treatment of psoriasis with a broad effect on multiple cell types involved in the development and progression of the disease

Evaluation of an anti-inflammatory dendrimer to topically treat psoriasis

International audiencePsoriasis is an auto-immune disease resulting from a chronic and exaggerated inflammation of the skin and hyperproliferation of keratinocytes. Conventional topical treatments for this disease, such as anti-inflammatory drugs, present low efficiency, and systemic administration of synthetic drugs or biologic immunomodulators can present severe side effects and/or are highly expensive. So, there is an unmet need to develop new drugs that could provide sustainable therapeutic effects. In this study, we evaluated the potential efficacy of anti-inflammatory dendrimers for the topical treatment of psoriasis. Dendrimers are hyperbranched and perfectly defined macromolecules of nanometer size, constituted of branches grafted on a central core. IMD-006, a phosphorus-based dendrimer capped with azabisphosphonate groups, has strong immuno-modulatory effects towards different immune cell types. Wetested the effects of IMD-006 in two psoriasis models: the imiquimod- induced murine model and a reconstructed human epidermis (RHE) model, in which cocktails of pro-inflammatory cytokines are used to induce psoriasis-associated changes. IMD-006 presented dose-dependent therapeutic efficacies, significantly reducing lesions and histopathological changes associated with psoriasis. Moreover, we show that IMD-006 is rapidly taken up by kerati-nocytes in 2D culture, decreasing their proliferation and increasing their differentiation. In keratinocytes in 2D culture, IMD-006 associated with mitochondria, increased mitochondrial ROS production and ultimately lysosomal degradation of these organelles. Therefore, the anti-psoriatic effect of dendrimers is, at least in part, the result of a direct effect on keratinocytes. Our results demonstrate that anti-inflammatory dendrimers are good candidates forthe topical treatment of psoriasis with a broad effect on multiple cell types involved in the development and progression of the disease