View clinical trials related to Innate Immunity.
Filter by:The ongoing pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) has infected more than one hundred twenty million peoples worldwide one year after its onset with a case-fatality rate of almost 2%. The disease due to the coronavirus 2019 (i.e., COVID-19) is associated with a wide range of clinical symptoms. As the primary site of viral invasion is the upper respiratory airways, lung infection is the most common complication. Most infected patients are asymptomatic or experience mild or moderate form of the disease (80 %). A lower proportion (15%) develop severe pneumonia with variable level of hypoxia that may required hospitalization for oxygen therapy. In the most severe cases (5%), patients evolve towards critical illness with organ failure such as the acute respiratory distress syndrome (ARDS). At this stage, invasive mechanical ventilation is required in almost 70 % and the hospital mortality rises to 37 %. Immune cells are key players during SARS CoV-2 infection and several alterations have been reported including lymphocytes (T, B and NK) and monocytes depletion, and cells exhaustion. Such alterations were much more pronounced in patients with the most severe form of the disease. Beside, a dysregulated proinflammatory response has also been pointed out as a potential mechanism of lung damage. Finally, COVID-19 is associated with an unexpectedly high incidence of thrombosis which probably results from the viral invasion of endothelial cells. The investigators aim to explore prospectively the alterations of innate and adaptive immune cells during both the acute and the recovery phase of SARS CoV-2 pneumonia. Flow and Spectral cytometry will be used to perform deep subset profiling focusing on T, B, NK, NKT, gamma-gelta T, monocytes and dendritic cells. Each specific cell type will be further characterized using markers of activation/inhibition, maturation/differenciation and senescence as well as chemokines receptors. T-cell memory specificity will be explore using specific SARS CoV-2 pentamer. Platelet activation and circulating microparticles will be explore using flow cytometry. Serum SARS CoV-2 antibodies (IgA, IgM, IgG), serum cytokines, and serum biomarkers of alveolar epithelial and endothelial cells will be analyze using ELISA and correlate with the severity of the disease.
Community acquired pneumonia (CAP) is a major cause of morbidity and mortality worldwide. Despite recent improvement in acute management (specifically for administration of antibiotics) many severe presentations of pneumonia worsen, progressing to Acute Respiratory Distress Syndrome (ARDS), a clinical entity with 40% hospital mortality. Dysregulation of immune response is thought to be largely implicated in severe pneumonia progressing to ARDS. Notably, experimental studies have recently suggested the implication of non-conventional T lymphocytes and innate cells in this immunopathology. However, no data are available in Humans in clinical settings. This study aims to explore the role of non-conventional T cells in pneumonia and ARDS, in participants. For this purpose, 100 participants admitted to Intensive Care Unit (ICU) with a diagnosis of CAP will be included, and 50 "control" participants with no pneumonia nor shock. Presence and functionality of non-conventional T cells and innate cells will be explored using flow-cytometry and ex-vivo stimulation, alongside with cytokines productions. These analyses are conducted in the blood, and, for invasively ventilated participants, in tracheal aspirates or broncho-alveolar fluids if available. For each participants included, the analyses are conducted at different time-points during ICU stay: inclusion, day 3, day 8 and day 15. Moreover, participants with ARDS, for whom a post-ICU follow-up program is normally established after discharge, will have blood analysis from blood samples taken during the follow-up visit up to 8 months after inclusion. Immunophenotypage and functionality of non-conventional T cells and innate cells will be compared to clinical parameters and their evolution, between "CAP" participants and "Control" participants", and for each participants, according to the different time-point of analysis, in order to better understand dynamic of innate immunity during pneumonia and ARDS.