4 results on '"Garnier, Lorna"'
Search Results
2. Monitoring monocyte HLA-DR expression and CD4 + T lymphocyte count in dexamethasone-treated severe COVID-19 patients.
- Author
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Monneret, Guillaume, Voirin, Nicolas, Richard, Jean-Christophe, Cour, Martin, Rimmelé, Thomas, Garnier, Lorna, Yonis, Hodane, Coudereau, Remy, Gossez, Morgane, Malcus, Christophe, Wallet, Florent, Delignette, Marie-Charlotte, Dailler, Frederic, Buisson, Marielle, Argaud, Laurent, Lukaszewicz, Anne-Claire, Venet, Fabienne, Pescarmona, Remi, Lombard, Christine, and Perret, Magali
- Subjects
RISK assessment ,PEARSON correlation (Statistics) ,MONOCYTES ,RESEARCH funding ,CRITICALLY ill ,PATIENTS ,CD4 lymphocyte count ,BACTEREMIA ,SCIENTIFIC observation ,FISHER exact test ,HOSPITAL mortality ,MULTIVARIATE analysis ,AGE distribution ,DESCRIPTIVE statistics ,CHI-squared test ,MANN Whitney U Test ,ODDS ratio ,GENE expression profiling ,INTENSIVE care units ,STATISTICS ,PATIENT monitoring ,LENGTH of stay in hospitals ,CONFIDENCE intervals ,COVID-19 ,DEXAMETHASONE ,BIOMARKERS ,HLA-B27 antigen ,COMORBIDITY ,IMMUNOSUPPRESSION ,REGRESSION analysis ,PROPORTIONAL hazards models ,DISEASE risk factors - Abstract
Background: A 10-day dexamethasone regimen has emerged as the internationally adopted standard-of-care for severe COVID-19 patients. However, the immune response triggered by SARS-CoV-2 infection remains a complex and dynamic phenomenon, leading to various immune profiles and trajectories. The immune status of severe COVID-19 patients following complete dexamethasone treatment has yet to be thoroughly documented. Results: To analyze monocyte HLA-DR expression (mHLA-DR) and CD4 + T lymphocyte count (CD4) in critically ill COVID-19 patients after a dexamethasone course and evaluate their association with 28-day ICU mortality, adult COVID-19 patients (n = 176) with an ICU length of stay of at least 10 days and under dexamethasone treatment were included. Associations between each biomarker value (or in combination) measured at day 10 after ICU admission and 28-day mortality in ICU were evaluated. At day 10, the majority of patients presented decreased values of both parameters. A significant association between low mHLA-DR and 28-day mortality was observed. This association remained significant in a multivariate analysis including age, comorbidities or pre-existing immunosuppression (adjusted Hazard ratio (aHR) = 2.86 [1.30–6.32], p = 0.009). Similar results were obtained with decreased CD4 + T cell count (aHR = 2.10 [1.09–4.04], p = 0.027). When combining these biomarkers, patients with both decreased mHLA-DR and low CD4 presented with an independent and significant elevated risk of 28-day mortality (i.e., 60%, aHR = 4.83 (1.72–13.57), p = 0.001). Conclusions: By using standardized immunomonitoring tools available in clinical practice, it is possible to identify a subgroup of patients at high risk of mortality at the end of a 10-day dexamethasone treatment. This emphasizes the significance of integrating immune monitoring into the surveillance of intensive care patients in order to guide further immumodulation approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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3. Recombinant human interleukin-7 reverses T cell exhaustion ex vivo in critically ill COVID-19 patients.
- Author
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Bidar, Frank, Hamada, Sarah, Gossez, Morgane, Coudereau, Remy, Lopez, Jonathan, Cazalis, Marie-Angelique, Tardiveau, Claire, Brengel-Pesce, Karen, Mommert, Marine, Buisson, Marielle, Conti, Filippo, Rimmelé, Thomas, Lukaszewicz, Anne-Claire, Argaud, Laurent, Cour, Martin, Monneret, Guillaume, Venet, Fabienne, RICO Study Group, Pescarmona, Remi, and Garnier, Lorna
- Subjects
COVID-19 ,T cells ,MONONUCLEAR leukocytes ,INTERLEUKIN-7 ,CRITICALLY ill ,T-cell exhaustion - Abstract
Background: Lymphopenia is a hallmark of severe coronavirus disease 19 (COVID-19). Similar alterations have been described in bacterial sepsis and therapeutic strategies targeting T cell function such as recombinant human interleukin 7 (rhIL-7) have been proposed in this clinical context. As COVID-19 is a viral sepsis, the objectives of this study were to characterize T lymphocyte response over time in severe COVID-19 patients and to assess the effect of ex vivo administration of rhIL-7. Results: Peripheral blood mononuclear cells from COVID-19 patients hospitalized in intensive care unit (ICU) were collected at admission and after 20 days. Transcriptomic profile was evaluated through NanoString technology. Inhibitory immune checkpoints expressions were determined by flow cytometry. T lymphocyte proliferation and IFN-γ production were evaluated after ex vivo stimulation in the presence or not of rhIL-7. COVID-19 ICU patients were markedly lymphopenic at admission. Mononuclear cells presented with inhibited transcriptomic profile prevalently with impaired T cell activation pathways. CD4 + and CD8 + T cells presented with over-expression of co-inhibitory molecules PD-1, PD-L1, CTLA-4 and TIM-3. CD4 + and CD8 + T cell proliferation and IFN-γ production were markedly altered in samples collected at ICU admission. These alterations, characteristic of a T cell exhaustion state, were more pronounced at ICU admission and alleviated over time. Treatment with rhIL-7 ex vivo significantly improved both T cell proliferation and IFN-γ production in cells from COVID-19 patients. Conclusions: Severe COVID-19 patients present with features of profound T cell exhaustion upon ICU admission which can be reversed ex vivo by rhIL-7. These results reinforce our understanding of severe COVID-19 pathophysiology and opens novel therapeutic avenues to treat such critically ill patients based of immunomodulation approaches. Defining the appropriate timing for initiating such immune-adjuvant therapy in clinical setting and the pertinent markers for a careful selection of patients are now warranted to confirm the ex vivo results described so far. Trial registration ClinicalTrials.gov identifier: NCT04392401 Registered 18 May 2020, http:// clinicaltrials.gov/ct2/show/NCT04392401. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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4. Correction to: Recombinant human interleukin-7 reverses T cell exhaustion ex vivo in critically ill COVID-19 patients.
- Author
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Bidar, Frank, Hamada, Sarah, Gossez, Morgane, Coudereau, Remy, Lopez, Jonathan, Cazalis, Marie-Angelique, Tardiveau, Claire, Brengel-Pesce, Karen, Mommert, Marine, Buisson, Marielle, Conti, Filippo, Rimmelé, Thomas, Lukaszewicz, Anne-Claire, Argaud, Laurent, Cour, Martin, Monneret, Guillaume, Venet, Fabienne, RICO Study Group, Pescarmona, Remi, and Garnier, Lorna
- Subjects
COVID-19 ,T cells ,INTERLEUKIN-7 ,CRITICALLY ill ,HUMAN beings - Abstract
RNA extracted from PBMCs of COVID-19 patients at day 0 and day 20 (n = 10) and healthy volunteers (HV, n = 10) was analyzed through NanoString technology. a Volcano plots of differentially expressed genes between patients sampled at D0 or at D20 and HV are showed. Reference 1 Bidar F, Hamada S, Gossez M, Coudereau R, Lopez J, Cazalis M-A, Tardiveau C, Brengel-Pesce K, Mommert M, Buisson M, Conti F, Rimmelé T, Lukaszewicz A-C, Argaud L, Cour M, Monneret G, Venet F. Recombinant human interleukin-7 reverses T cell exhaustion ex vivo in critically ill COVID-19 patients, for the RICO study group. [Extracted from the article]
- Published
- 2022
- Full Text
- View/download PDF
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