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Health disparities in infectious disease may be driven by poverty, access to care, and social and environmental risk factors. In public health emergencies such as the COVID-19 pandemic, populations at increased risk of severe outcomes are disproportionately impacted by both the direct outcomes of disease and its cascading social and economic consequences. While individual factors, such as comorbidities and health behavior, impact the risk of disease, research on past pandemics reveals the substantial and sometimes greater impact of structural factors, including access to care and social and environmental systems on the disproportionate rates of disease and death in marginalized populations. Within these systems, environmental determinants of infectious disease transmission and severity, including environmental hazards and the impacts of climate, housing, and infrastructure, are a critical area for study and prevention. The intersection of environmental and social stressors has been highlighted by environmental justice advocates and scientific researchers and may manifest through the pathways of structural racism and discriminatory policy, including in high risk settings like the US carceral system.Throughout the COVID-19 pandemic, prisons and jails have experienced alarmingly high rates of disease and mortality and disruptions to critical education, legal, and mental health services. Overcrowding, limited access to medical services and information, in combination with intersecting risks of poverty, lower educational attainment, and racial health disparities, place incarcerated residents and staff at both a higher risk of acquiring COVID-19 and subsequent adverse outcomes including death. Moreover, substantial differences in transmissibility and severity of emergent variants have complicated our understanding of the relative importance of various risk factors as well as of the relative effectiveness of vaccines, a critical public health tool for primary prevention of COVID-related infection and illness. Although incarcerated people remain at high risk of disruptive outbreaks and poor outcomes, robust analytic studies of COVID-19 in this population are limited. It is of urgent public health importance to understand the factors associated with transmission and severity so to develop policy that is both effective and reflects the complexity of the prison system.Outside of prisons, researchers have noted spatially distributed COVID-19 disparities along racial, socioeconomic, and health care access lines. In the broader community, a wide body of research has highlighted the potential role of air pollution in increasing the risk of severe COVID-19 through direct harms to the lungs, through increased risk of other chronic diseases, and through the persistence of viral particles in the air. Oil and gas production activities are a significant and under-examined source of air pollution, including NO2 and PM2.5, in addition to other types of pollution, and have been linked to respiratory and immunologic disease. They are also widespread: across the globe, over 600 million people are estimated to live near oil and gas development, many of whom are also likely to be marginalized populations and disproportionately exposed to both pollutants and social stressors that may cumulatively impact health.To study the intersection between these environmental factors and COVID-19 outcomes, I conducted a series of observational studies in California. In Chapter 1, I relate the results of an outbreak investigation and subsequent analysis of the first large COVID-19 outbreak in the California state prison system following widespread availability of vaccines (May 2021). At the time of the outbreak, around half of residents in the study cohort had received at least one dose of a SARS-CoV-2 vaccine. The results showed that individual vaccine effectiveness against testing positive for SARS-CoV-2 with a PCR test was 86% (Hazard ratio (HR): 0.14, 95% CI: 0.07, 0.25), comparable to estimates in the general population against the Alpha variant (B.1.1.7). In the examination of indirect effects, exposure to a vaccinated cellmate may have conferred some protection to unvaccinated individuals (HR: 0.62, 95% CI: 0.37, 1.04). However, stronger results were found at the building level: higher proportions of vaccinated residents in each building were non-significantly associated with lower building case rate (HR: 0.21, 95% CI: 0.04, 1.16). While the small size of the study increases uncertainty in these findings, these results may suggest that herd immunity plays a stronger role in interrupting transmission than vaccination of close contacts, even when residents are housed in two-person, solid door cells. In Chapter 2, I collected information on door type and housing infrastructure (i.e., cell, dormitory) for California state prisons. Using daily health and residential housing data, I identified a cohort of over 150,000 state prison residents from March 2020 to February 2022 and developed five categories of residential housing based on cell/dormitory infrastructure and the presence of a solid door, of a partial or barred door allowing significant airflow, or no door at all. In this study, most residents lived in celled housing with solid doors or single-room dormitories with no doors. Ordered by population size at baseline, residents also lived in multi-room dormitories (“pods”) with solid doors, multi-room dormitories with partial doors, and celled housing with barred doors. After accounting for individual and prison-level covariates, residents of celled buildings with solid doors had the lowest rates of PCR-positive SARS-CoV-2, with all other types having between 1.5 and 2 times higher rates of infection. However, there was not a clear gradient of risk across housing types based on the separation of residents into rooms of different sizes (with dormitories being larger than cells) and by door type, and we observed moderate differences in the relative rates of infection when time points accounting for seasonal changes and new variants were considered. In comparison to the reported case rates of California, at nearly all time periods, infection rates in even the “safest” housing with the greatest degree of separation (celled housing with solid doors) greatly exceeded the general population. These results suggest that the physical environment of prisons affects respiratory disease transmission above and beyond individual risk factors, and that residents remain at elevated risk of harm, particularly in outbreaks or in times of limited space, testing, or medical resources. Infection control in prisons must address the availability of separated housing, the mental, social, and legal consequences of moving and isolating residents, and must identify and investigate other forms of hazard reduction, including depopulation, to reduce harms.In Chapter 3, I conducted an ecological study to estimate the association between block group level exposure to oil and gas well production and reported COVID-19 case rates and mortality in California. We restricted the study population to residents of block groups within 10 kilometers of an active well using high-resolution geographical population estimates. For block groups within 1 kilometer of active wells, average annual production was estimated for all neighboring oil and gas wells between 2018 and 2020 as a proxy measure of long-term exposure to air pollutants, and production was categorized into tertiles. In our analysis of four-month time periods, in the first (February-March 2020) but not in subsequent time periods, we observed a significant association between production level and both case and mortality rates. As testing was limited at this time, these results suggest that if there is a true effect, it may be on progression to symptomatic and severe disease that would have been more likely to be detected. Across the entire study period, we did not observe an association between estimated production and COVID-19 case and mortality rates, except for mortality at the highest level of production. Overall, after consideration of area-level socioeconomic, urbanicity, and other covariates, we observed inconsistent associations between oil and gas production level and reported COVID-19 elevated case and mortality rates in these communities that was time-specific; our results indicate the need for further research on the geographic and environmental determinants of COVID-19. In summary, this dissertation provides evidence around susceptibility and severity of respiratory disease, and specifically COVID-19, in understudied populations with environmental risk factors. The findings related to vaccination and the high rates of infection across even the “safest” prison setting emphasize the prioritization of the carceral population in vaccination, testing, and public health resource allocation in emergency settings, and revisiting the ways in which the carceral environment negatively and unacceptably affects health. Across all studies, our findings emphasize the specific consideration of social and environmental stressors in equitable pandemic preparedness planning and contribute to the broader literature around environmental determinants of infectious disease and related health disparities.