The main idea behind this project is to interrogate SARS-CoV-2 infection using an integrated cross-disciplinary approach that includes characterizing and modeling host-virus interactions to addressing how these shape virus pathogenesis and evolution in vivo. Our team has different expertise and backgrounds, ranging from hardware and software engineering for animal monitoring, virus evolution and single-cell transcriptomics to mathematical modeling. The significance is twofold: (1) To better understand SARS-CoV-2 interactions and lead to new and much-needed therapies to control SARS-CoV-2 infections and (2) to establish a new animal model paradigm for studying SARS-CoV-2-host dynamics in an integrative fashion.

We use experimental and computational platforms that will merge system immunology, virus replication and disease progression modeling, and external monitoring with virus replication, evolution, and pathogenesis studies. Linking these different but complementary approaches will yield a powerful platform to understand and dissect the fundamental principles of SARS-CoV-2 pathogenesis and strategies that drive virus evolution and diversity. Ultimately, the goal of this project is to use animal models, such as Ace2-tg mice and Golden Syrian hamsters (SARS-CoV-2 Spike protein binds to hACE2 receptor for viral entry in the cell) to accelerate the development of effective and safe SARS-CoV-2 vaccine strategies and antiviral drugs.

We work with the laboratory of Dr. Hiten Madhani to also generate, validate, and utilized a pseudotyped version of the SARS-CoV-2 virus.

We have identified a representative cohort of 300 individuals (100 confirmed coronavirus disease 2019 [COVID-19] cases from the Departments of Public Health [DPH]; 200 contacts of cases) in the San Francisco Bay Area. After enrolling a case, we will recruit the case’s household in order to identify contacts who are at high risk for COVID-19. We intend to identify uninfected, exposed individuals as close to a SARS-CoV-2 exposure as possible so that we can determine when viral shedding starts. We will use contact tracing to enrich our sample with special populations.