Mononuclear phagocyte differentiation trajectories driving a cytokine storm and tissue damage in COVID-19 (B09*)

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The cause of a cytokine storm in SARS-CoV-2 infection is unclear but severe COVID-19 is associated with myeloid cell dysregulation, indicating mononuclear phagocytes are important players. We have previously studied macrophage differentiation towards pro- versus anti-inflammatory macrophages in mouse models of influenza and in infected organoids and identified type I interferons as major drivers of lung tissue injury in viral pneumonia (SH group). We furthermore recently identified drivers of a macrophage activation syndrome induced by high levels of type I interferons in lupus-prone mice (AT group). Here we propose to employ our current understanding of the pathways leading to macrophage hyperactivation to identify pathways driving a cytokine storm in COVID-19. Our goal is to begin to shed light to the mechanistic underpinnings of mononuclear phagocyte hyperactivation, alveolar damage and endothelial dysfunction in COVID-19.