Disregulation of inflammasome' activation in neutrophil and endothelium in response to SARS-Cov-2 and contribution to severe COVID-19

The COVID 19 pandemic is caused by the emerging virus SARS-COV-2 and is responsible for more than 1 million deaths worldwide. The immunopathology of COVID-19 is characterized by a systemic inflammation with significant hematological changes such as neutrophilia and lymphopenia and an exacerbated production of inflammatory cytokines responsible for a viral sepsis in the most severe cases of the disease. IL 1² and IL 18 stand out among the cytokines markedly deregulated during the infection by SARS-COV-2 and both are produced with inflammasome activation The inflammasome is a multiprotein complex activated in response to several PAMPs and DAMPs pathogen and damage associated molecular pattern which are recognized by different cytosolic receptors as NLRP3 the most well known and studied. In the context of SARS COV 2 infection, recent data point to a direct NLRP3 activation in macrophages, however little is known about a possible activation of NLRP3 in other cell types such as neutrophils or endothelial cells. Recent studies indicate that both cells are capable of activating the NLRP3 inflammasome and are involved in the pathogenesis of several infectious diseases, inflammatory and coagulopathies similar to COVID-19 manifestations. In this sense, we intend to investigate the profile of activation of NLRP3 inflammasome complex in neutrophils and endothelial cells with a focus on the severity of the disease as well as the role of inflammasome genetics in the interindividual variability of clinical manifestation, enabling not only a better understanding of the disease's immunopathogenesis but also the identification of possible therapeutic targets helping to face the pandemic.