PROJECT SUMMARY/ABSTRACT We propose to rapidly apply key assays of patient samples derived from IMPACC studies to understand the critical features that characterize hospitalized patients with COVID-19, a pandemic disease characterized by immune exacerbations of lung injury. These proposed studies are a natural and focused extension of the work we are performing in the parent U19 award adapted to the urgent medical need to better understand the pathogenesis of severe, life-threatening COVID-19 disease. We propose 5 site-specific studies that are highly complementary to assays being performed by the IMPACC national immunophenotyping cores here at UCSF and elsewhere. These include studies that focus on both airway cells and blood immune cells (including neutrophils) and utilize a set of innovative methods that allow for a detailed understanding of the nature and activation states of specific cell types within the airway and the blood. These studies promise to yield new insights relevant for understanding COVID-19 immunopathogenesis and predicting disease outcome and response to therapy, and could lead to novel therapeutic targets for this devastating disease.