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.
We hypothesize that there are patterns in the immune responses seen in COVID-19 patients that define those that are susceptible to developing ARDS. We will apply multiplexed CITE-seq and scRNA-seq to tracheal aspirates and blood, assay for NETS, and measure immune cell activation status in single cells taken from patients. These studies provide unique insights into the systemic immune system in patients that resolve or succumb to COVID-19.
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