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 >464 million infections and more than 6 million deaths worldwide in just over 2 years. Global sequencing efforts have identified several viral variants of concern (VOC) and interest (VOI) that result in increased transmission, virulence, vaccine escape, and/or increased mortality for those infected. Ongoing viral genomic surveillance is necessary to identify and characterize viral variants, to inform both ongoing public health efforts and future vaccine/treatment design strategies. This is a particularly urgent need for Institutional Development Award (IDeA) states, for which knowledge of circulating SARS-CoV-2 variants is relatively limited. The mechanistic forces driving SARS-CoV-2 diversification and variant emergence are certainly multifactorial. Recent reports suggest that biological sex and age 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 continues to be underreported. 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. Environmental surveillance efforts have also been developed to track SARS-CoV-2 spread at the population/community-level, providing minimally invasive, unbiased VOC detection at low cost. Integration of clinical surveillance data with wastewater (WW) monitoring programs will enrich both datasets, laying the groundwork for modeling how WW data may best be utilized as an early warning system for public health authorities. Despite the development of multiple robust and effective vaccines, ongoing viral evolution has resulted in resistance to current (and waning) levels of vaccine- mediated protection, and this pattern will likely continue with emerging VOCs. 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 ~6000 samples sourced across Kentucky (KY) to (1) substantially improve data availability regarding SARS-CoV-2 dynamics and variant circulation, investigating biological and geographical association with VOC dynamics, (2) integrate wastewater and clinical SARS-CoV-2 surveillance data, and (3) identify mutational signatures associated with clinically relevant SARS-CoV-2 infections.. To achieve this, we have built a multi-institutional collaborative effort, developing key partnerships among a deep network of academic, healthcare, private and public health stakeholders, positioning this team as a pathogen surveillance center for ongoing and future efforts.