COVID19 Admin Supplement to Rapidly Translate Immunobiology for Patient Benefit

This is an administrative supplement to the parent R01 AI052116 "SPATIOTEMPORAL CONTROL OF T CELLSYNAPSE STABILIZATION AND SIGNALING" which for my entire career has been my central grant forstudies of T cell interactions leading to tolerance or activation. Here, we apply our considerable immune andtissue-immune experience towards generating and exploiting a RapidPath platform to find rapid actionableimmunotherapeutic targets for COVID-19 patients for limiting damage due to SARS-CoV-2 infections.In aim 1 of this study, we will build a lung plus virus plus immune platform in which the role of specific T cells ofdifferent activation status -alone and through their modulation of myeloids cells-will be assessed in theresponse of damage to lung epithelium plus/minus endothelium (organoid, with Roose/Gordon and lung slicewith Looney). This supplement will interact intensely with parallel studies of those labs and also with ongoingstudies that will also leverage RapidPath but are not in this first cohort of applications. This will provide `best inclass' model systems in human biology and will leverage our collective expertise. In aim 2 of this study, wewill test a panel of immunomodulatory drugs to determine if acute exposure to them can modulate lungdamage, likely through modulating myeloid biology. The net result will be validated immunotherapeuticpaths in robust pre-clinical human systems that recapitulate key features of COVID-19.