COVID-19 and innate immune response : dysregulation of phagocyte functions during SARS-CoV2 infection – COVINNATE

First COVID-19 studies have pointed out an abnormal immune response in patients, particularly in severe cases. High concentrations of proinflammatory cytokines and chemokines, high number of neutrophils with low number of lymphocytes have been associated with the main causes of adverse outcome such as ARDS, kidney failure and coagulopathy. Furthermore, ICU patients frequently develop severe bacterial and fungal infections that are reminiscent of primary innate immune deficiencies like chronic granulomatous disease. These findings strongly suggest a role for neutrophils and monocytes in hyperinflammatory responses in COVID-19 pathogenesis, but also in the late immunodeficiency observed in some patients. Based on these findings we hypothesize that in severe COVID-19 overactivation of the innate system leads first to hyperinflammation and later on an exhaustion of cellular effectors responsible for secondary infections.
The goal of this proposal is to investigate the implication of phagocytes in COVID-19 pathogenesis and immune response, at various stages of the disease. Our project will deeply analyse main molecular effectors and functions of innate immune response in phagocytes during COVID-19 and their correlation with inflammatory markers and adverse clinical outcome. Most of the experiments will be done on fresh blood from the patients. Analysis of these results in terms of clinical severity, and the immunomodulatory drugs used, will allow us to propose adaptations of therapeutic strategies, in particular antibioprophylaxis and use of biologics, according to the innate system status.