Surveillance and identification of variants of concern within circulating SARS-CoV-2 across Kentucky

PROJECT SUMMARY The emergence and circulation of SARS-CoV-2, the virus that causes COVID-19 disease, has led to >125 million infections and more than 2.5 million deaths worldwide in just over 1 year. Global sequencing efforts have identified several viral variants of concern (VOC) and interest (VOI) that result in increased transmission rates and/or increased mortality for those infected with the new SARS-CoV-2 strains. Despite the development of multiple robust and effective vaccines, further viral evolution may result in resistance to current levels of vaccine- mediated protection. Ongoing viral genomic surveillance is necessary to identify and characterize known and new viral variants, to inform both ongoing public health efforts, and future vaccine design strategies. This is a particularly urgent need for Institutional Development Award (IDeA) states, for which knowledge of circulating SARS-CoV-2 variants is extremely limited. The mechanistic forces driving SARS-CoV-2 diversification and variant emergence are certainly multifactorial. Effective natural and vaccine antiviral protection is thought to be mediated by potent, broadly reactive neutralizing antibodies (nAbs). Recently developed genotyping assays have characterized the extensive diversity within immunoglobulin (IG) loci, with increasing evidence suggesting that the collective array of genes that encode antibody repertories differ widely across ethnic populations. Moreover, recent reports suggest that biological sex may impact immunopathogenesis and individual resilience, and that geographically restricted circulation and transmission of variants, along with pre-existing social vulnerabilities may also impact SARS-CoV-2 variant dynamics. It is well documented that COVID-19 disproportionately impacts underrepresented populations, including Black, Indigenous and people of color (BIPOC) and Latinx peoples. Data regarding SARS-CoV-2 circulation and variant profiling in these populations in also underreported in ongoing viral surveillance efforts. Evaluating how viral VOC and VOI are impacted by differential genetic, biological and social backgrounds will be critical for providing equitable representation of the frequency and characteristics of SARS-CoV-2 variants, and act as a first step towards mechanistic hypothesis generation for future studies. Using a robust, high throughput and cost-effective single molecule, real-time sequencing approach, we propose to perform large scale SARS-CoV-2 genomic surveillance from ~7000 samples sourced across Kentucky (KY) to (1) substantially improve data availability regarding SARS-CoV-2 dynamics and variant circulation, (2) evaluate biological and social correlates of variant emergence and evolution, and (3) leverage this pipeline to develop a unique curriculum in pathogen surveillance. To achieve this, we have built a multi- institutional collaborative effort, developing key partnerships among a deep network of academic, healthcare, and industrial stakeholders, positioning this team to establish a pathogen surveillance center for ongoing and future efforts.