Consequences of the timing the of type I interferons response on the clinical course and immune response to SARS-CoV-2 infection. – TIMING

Type I interferons are the main antiviral cytokines. They stimulate the expression of antiviral effectors and regulate the activation of various immune cells. However, type I interferons may not always be beneficial during a viral infection, as they can cause an excessive inflammation leading to immunopathology. In the case of COVID-19, the balance between the beneficial and the detrimental effects of type I interferons could be very precarious. Experimental studies in SARS-CoV-1 infected mice and clinical investigations in COVID-19 patients indicate that an early type I interferon response could be beneficial, while a delayed type I interferon response could be detrimental to the host. Thus, the timing of the type I interferon production could be a critical determinant of the pathophysiology of SARS-CoV-2 infection. The aim of the TIMING project is to test this hypothesis in an animal model of SARS-CoV-2 infection. We will administer type I interferon at various time points post-infection and investigate how the timing of the type I interferon response modulates the clinical course of infection. By combining virological analyses with profiling of the immune response, our project will lead to a better understanding of the pathophysiology of COVID-19 and may lead to the identification of biological markers that correlate with type I interferon therapeutic efficacy.