RFA-CK-22-008, TRANSMIT: Training Research Acumen in Students Modeling Infectious Threats

PROJECT SUMMARY/ABSTRACT The ongoing COVID-19 pandemic has overwhelmed healthcare and public health systems, underscoring the need to anticipate disease outbreaks and prepare resources such as hospital beds and staff. One cost-effective and timely way to prepare resources to respond to these outbreaks is through the use of mathematical modeling. Models can act as a virtual laboratory to explore a variety of scenarios, interventions, or applications in a timely manner to inform policy interventions. While the COVID-19 pandemic highlighted the gaps that models can fill, it also highlighted a considerable gap in modeling: there is a lack of modeling professionals trained in developing and applying transmission models to healthcare settings. In this proposal, we detail three projects aimed to train three predoctoral fellows in different aspects of mathematical modeling of healthcare associated pathogens. These projects tackle different pathogens and components of disease transmission in a healthcare setting; and, while each project is distinct, they dovetail nicely, resulting in a cohesive research program. Project 1 tackles a critical component of disease transmission in healthcare settings: COVID-19 in long-term care facilities (LTCFs). Throughout the pandemic, LTCFs bore a disproportionate burden of mortality. Yet, while it is clear that LTCFs important with regards to disease outcomes, whether or not they exert selective forces on SARS-CoV-2 that have shaped global patterns of pathogen evolution is not yet known. Here, we will develop models to quantify the phylogenetic relationships between community and long-term care facility lineages to understand the viral diversification attributable to healthcare settings. Project 2 explores the risk factors of patients hospitalized with SARS-CoV-2 for acquiring multi-drug resistant organisms (MDROs). The rapid spread of SARS-CoV-2 has changed to hospital infection control and antimicrobial stewardship policies. One such change has been widespread potentially unnecessary antibiotic use among hospitalized patients. Here, we will identify the characteristics of the sub-population disproportionately impacted by co-infections with MDROs for patients hospitalized with SARS- CoV-2. Project 3 integrates with both Project 1 and 2, to explore the evolution of antibiotic resistance due to variable dose and off-target antibiotic use in healthcare settings. Patients in hospitals and residents of LTCFs are exposed to a wide range of pathogens and treatments, and many of these organisms have themselves been exposed to a wide range of environmental antibiotics. Here, we will develop models of evolution to investigate the conditions that lead to the most intractable infections.