Antigen specific T cell responses to two different strains of SARS-CoV-2

PROJECT SUMMARYCoronavirus disease 2019 (COVID-19) is an emerging infectious disease that is caused by the SARS-CoV-2virus. The disease has caused illness in more than 1.2 million Americans within the last 4 months. However,there are almost no data on human cellular immune response towards this virus. Monitoring the kinetics andbreadth of cellular immune responses associated with clinical resolution of COVID-19 should shed insight on thehuman immune response towards this pathogen during natural infection. We will evaluate SARS-CoV-2 antigenspecific immune responses in subjects with different degree of disease severity that are infected by either theUSA-WAS2/2020 like strain or the FR-HF1465/2020 like strain, the 2 major strains that circulated in Washingtonstate. We will test the hypothesis that coordinated CD4+ and CD8+ antigen specific responses are responsiblefor clearing of the virus. We will also test the hypothesis that subjects that have severe disease and those thatsuccumb to the disease have dysfunctional CD4+T cell responses. We will use transcriptomics analysis toevaluate whole blood, bulk T cells and antigen specific CD4+ and CD8+ T cells. Data will be stratified accordingto the viral strains and disease severity. There will be 3 major aims: 1. Characterize of antigen specific immuneresponses in COVID-19 subjects with severe pneumonia, moderate disease and mild disease, infected by eitherthe USA-WAS2/2020 strain or the FR-HF1465/2020 strain. 2. Characterize epitope specific immune responsein subjects with COVID-19. The hypothesis that the functional defect of antigen specific CD4+ T cells in subjectswith severe disease will be tested. 3. Characterize host RNA-seq signatures of COVID-19 respiratory infectionin whole blood PBMC, bulk and viral antigen-specific CD4+ and CD8+ T cells from COVID-19 subjects infectedby either the USA-WAS2/2020 strain or the FR-HF1465/2020 like strain. A better understanding of antigenspecific immune responses in human should facilitate the identification of effective drug candidates for treatmentand developing new vaccine to prevent infection.