GENOMIC APPROACHES TO UNDERSTAND DISEASE SUSCEPTIBILITY AND PATHOGENESIS OF SARS-COV-2

OVERALL PROJECT Summary: The novel coronavirus, SARS-CoV-2, that was first detected in China in December 2019 has now spreadglobally. The Texas Medical Center in Houston, TX, the fourth largest city in the US, and among the top 10 inracial diversity, mounted an aggressive early response to the pandemic, primarily focused on acute care. WithinBaylor College of Medicine, members of the TMC - Genomic Center for Infectious Disease (TMC-GCID) program(https://gcid.research.bcm.edu/overview) are leveraging existing infrastructure, together with an active androbust sample collection stream linked to both clinical and community testing, to characterize SARS-CoV-2virulence and susceptibility across the region. This application requests supplemental funding to the TMC-GCIDto help support SARS-CoV-2 community-wide surveillance, complete viral genome sequencing, nasopharyngealmicrobiome profiling, and targeted host genetic analyses. The primary objective of this supplement will beachieved through the collaborative efforts of a multidisciplinary, integrated team of basic and physician scientistswith a track-record of collaboration and who are already delivering on the primary goals of the TMC-GCID. Theoverall goals of our GCID supplement is to study the biology of SARS-CoV-2 infection, the host andmicrobial genetics associated with disease, and to address community needs, particularly inunderserved communities, through the following aims: i) expand an operational Emergency UseAuthorization- (EUA-) and IRB-compliant COVID-19 qPCR screening/surveillance program featuringonline enrollment and consent as well as HIPAA-compliant return of results, ii) sequence and analyzefull-length SARS-CoV-2 genomes from infected individuals collected from the TMC and surroundingarea, iii) identify microbial co-colonization/co-infections that predict COVID-19 disease severity and/oroutcome, iv) Characterize the host genetic variation with respect to viral titer, disease severity, andoutcome in patients positive for COVID-19, including polymorphisms in human leukocyte antigen (HLA),angiotensin-converting enzyme 2 (ACE2), and natural killer cell immunoglobulin-like receptor (KIR)regions. This supplement will leverage the cutting edge, high-throughput sequencing strategies andtechnologies supplied by the TMC-GCID Sequencing Technology (ST) Core, in generating discoveries, data,tools, and reagents that will be analyzed and disseminated to the infectious disease community through theTMC-GCID Data Management Analysis and Resource Dissemination (DMARD) Core. The result will be acomprehensive genetic profiling of hosts and microbes in SARS-CoV-2 infection that will reveal pathogen geneticvariants associated with individual host response phenotypes that will inform precision medicine-basedtherapeutics and diagnostics, not just for SARS-CoV-2, but for other pandemic threats that we have alreadyobserved to profoundly change the world around us.