OVERALL PROJECT SUMMARY The novel coronavirus, SARS-CoV-2, that was first detected in China in December 2019 has now spread globally. The Texas Medical Center in Houston, TX, the fourth largest city in the US, and among the top 10 in racial diversity, mounted an aggressive early response to the pandemic, primarily focused on acute care. Within Baylor 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 and robust sample collection stream linked to both clinical and community testing, to characterize SARS-CoV-2 virulence and susceptibility across the region. This application requests supplemental funding to the TMC-GCID to help support SARS-CoV-2 community-wide surveillance, complete viral genome sequencing, nasopharyngeal microbiome profiling, and targeted host genetic analyses. The primary objective of this supplement will be achieved through the collaborative efforts of a multidisciplinary, integrated team of basic and physician scientists with a track-record of collaboration and who are already delivering on the primary goals of the TMC-GCID. The overall goals of our GCID supplement is to study the biology of SARS-CoV-2 infection, the host and microbial genetics associated with disease, and to address community needs, particularly in underserved communities, through the following aims: i) expand an operational Emergency Use Authorization- (EUA-) and IRB-compliant COVID-19 qPCR screening/surveillance program featuring online enrollment and consent as well as HIPAA-compliant return of results, ii) sequence and analyze full-length SARS-CoV-2 genomes from infected individuals collected from the TMC and surrounding area, iii) identify microbial co-colonization/co-infections that predict COVID-19 disease severity and/or outcome, iv) Characterize the host genetic variation with respect to viral titer, disease severity, and outcome 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 and technologies 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 the TMC-GCID Data Management Analysis and Resource Dissemination (DMARD) Core. The result will be a comprehensive genetic profiling of hosts and microbes in SARS-CoV-2 infection that will reveal pathogen genetic variants associated with individual host response phenotypes that will inform precision medicine-based therapeutics and diagnostics, not just for SARS-CoV-2, but for other pandemic threats that we have already observed to profoundly change the world around us.