Evolution, transmission, and clinical impacts of SARS-CoV-2 variants among urban and rural populations

Project Summary The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has resulted in over 5 million deaths worldwide. As the burdens of the pandemic in the United States (US) shift from urban to rural communities, preliminary studies suggest that rural populations suffer from higher disease severity and mortality rates than urban populations. However, even while 20% of the US population lives in a rural area and rural populations have known risk factors that differ from urban populations, the majority of COVID-19 research has primarily focused on large urban centers, and disease mitigation efforts in rural communities are largely informed by urban-centric data. Thus, it is urgently necessary to understand the evolution, spread, and clinical impacts of SARS-CoV-2 variants in rural areas and the disease interactions among urban and rural regions. However, limited clinical and genomic data, particularly from rural areas, are available, preventing us from fully understanding the disease dynamics of COVID-19. The objectives of this training grant are to determine how SARS-CoV-2 variants emerge and spread among urban and rural communities and to determine the virus, host, and population factors associated with clinical outcomes while training an MD-PhD student in advanced bioinformatics approaches, translational study design, and computational thinking to become an independent physician scientist. The Central Hypotheses are that SARS-CoV-2 variants arise in urban centers and spread into rural environments and that a synergistic set of virus, host, and population factors are associated with disease severity. To test our hypotheses, two specific aims are proposed to determine the genetic diversity and spread of SARS-CoV-2 variants among urban and rural regions (Aim 1) and to model clinical impacts of host, SARS-CoV-2 virus, and population factors (Aim 2). An existing and ongoing multi-year dataset that includes clinical information and whole genome sequencing of COVID-19-positive samples of individuals from urban and rural regions of Missouri will be used in both aims. This proposal is submitted in response to the NIAID Strategic Plan for COVID-19 Research Priority 1, "Assess functional consequences of newly emerging SARS-CoV-2 variants." We expect the results from this study to support this priority in two ways: 1) We will determine the transmission patterns of SARS-CoV-2 variants between urban and rural communities, and 2) We will determine the clinical implications of existing and emerging SARS-CoV-2 variants as they interact with various other virus and host factors. The results from this project will improve the understanding of SARS-CoV-2 transmission dynamics and clinical impacts, particularly among rural populations, which will be important for the mitigation of COVID-19 and future pandemics.