NCT04385017

Role of Inflammasomes in COVID-19 Disease

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 99 (actual)
• Sponsor: Centre Hospitalier Universitaire de Nice · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

As of March 25, 2020, 414,179 cases and 18,440 deaths secondary to Coronavirus 2019 disease (COVID-19) have been reported worldwide. The unfavorable course of the patients is characterized on the immunological level by an intense pro-inflammatory response which can go as far as a cytokinic storm. This pandemic affects a naive world population from an immunological point of view with respect to SARS-CoV-2 responsible for COVID-19. The evolution is favorable without hospitalization in almost 85% of cases. Among patients hospitalized for pneumonia, some will not require ventilatory support while others will need intensive care. To date, two main types of unfavorable evolution have been described. The first is a bi-phasic evolution beginning with a paucisymptomatic form which is worsened secondarily with respiratory distress associated with a decrease in the viral load in the airways. The second is associated with persistent high viral loads in the airways and detection of the virus in the blood. These different clinical profiles could depend on the quantitative and qualitative response of the innate immune system. At the early stage of a viral infection the innate immunity is capable of detecting certain conserved microbial patterns (PAMP, pathogen-associated molecular pattern) recognized by receptors dedicated to these patterns (PRR, pattern recognition receptor). This process allows to initiate the pro-inflammatory response via different signaling pathways. Activating multiprotein complexes called inflammasomes, which cause pro-IL-1β and pro-IL-18 to be transformed into active pro-inflammatory cytokines are one of these pathways. The central role of inflammasomes in the secretion of these pro-inflammatory cytokines deserves an in-depth study of their activation during COVID-19, whereas the inadequate inflammatory response appears to be the determining factor in the unfavorable development of patients. The objective of this project is to analyze the level of activation of the inflammasomes and then to search for inactivating or activating mutations among the genes which code for the proteins constituting the inflammasomes in Covid-19 patients. The identification of mutations in patients with a serious clinical presentation or even death would be followed by fundamental work by analyzing in a cellular model the impact of these mutations on the secretion of IL-1β.

Conditions

• COVID-19 by SARS-CoV-2 Infection

Interventions

Type	Name	Description
OTHER	COVID-19 patients	It will consist in the collection of 2 additional tubes at their blood draw. For DNA analysis, informed consent will be collected in writing

Timeline

• Start date: 2020-05-11
• Primary completion: 2022-02-01
• Completion: 2022-12-30
• First posted: 2020-05-12
• Last updated: 2023-03-22

Locations

2 sites across 1 country: France