2025 Theses Doctoral

The Role of Cardiovascular Morbidity in the Relationship between Ambient Air Pollution Exposure and Adverse COVID-19 Outcomes

Kannoth, Sneha

The COVID-19 pandemic elucidated geographical disparities in COVID-19 burden on a globalscale. Geographical disparities in adverse COVID-19 outcomes may suggest population-level drivers of disease, such as environmental exposures. Epidemiological literature provides strong evidence that greater exposure to ambient air pollution, an environmental exposure, is associated with a greater risk of COVID-19 hospitalization and fatality. The pathways by which ambient air pollution exposure influences adverse COVID-19 outcomes are currently unknown. I propose that cardiovascular morbidity is relevant in this pathway, given that cardiovascular morbidity is a predominant risk factor of adverse COVID-19 outcomes, and there are strong and consistent associations between air pollution and cardiovascular morbidity. I suggest that the role of cardiovascular morbidity will be different for historical air pollution (period > 30 days) and short-term air pollution (period < 30 days). By proposing clear causal structures for the relationship between air pollution and adverse COVID-19 outcomes, we can explicate how air pollution leads to greater COVID-19 burden and address the larger goal of reducing geographic disparities in adverse COVID-19 outcomes.

This dissertation is comprised of three specific aims. For the first aim, I performed a systematic review of the literature that examined the relationship between ambient air pollution and individual-level adverse COVID-19 outcomes. I identified if and how researchers conceptualized the causal role of comorbidities, specifically cardiovascular morbidities, in the relationship between air pollution and adverse COVID-19 outcomes. For the second aim, I examined if cardiovascular morbidity mediates the relationship between historical air pollution and adverse COVID-19 outcomes. For the third aim, I examined if there was evidence of synergistic interaction between short-term air pollution and cardiovascular morbidity in influencing the risk of adverse COVID-19 outcomes, suggesting that the effect of both short-term air pollution and cardiovascular morbidity on adverse COVID-19 is greater than the sum of the individual effects.

In conducting the first aim, I used Covidence, a software used to manage systematic reviewstudies, to identify studies that examined the relationship between ambient air pollution exposure and individual-level adverse COVID-19, using the Embase, MEDLINE, and Web of Science databases. In conducting the empirical aims, I used a retrospective cohort study design using INSIGHT-Clinical Research Network (CRN) data, a harmonized repository of inpatient electronic health records in New York City (NYC) across metropolitan healthcare systems (3/1/2020-2/28/2021). INSIGHT-CRN included data pertaining to sociodemographics, diagnoses, outcomes, and residential ZIP Code to link air pollution exposure.

For the second aim, I used the New York City Community Air Survey (NYCCAS) to estimate historical air pollution exposure to particulate matter (PM2.5), black carbon (BC), nitrogen dioxide (NO₂), and ozone (O₃) on a ZIP Code level (2009-2019). For the third aim, I used the 2020 Environmental Protection Agency (EPA) Community Multiscale Air Quality (CMAQ) downscaler modeled data, which estimated 2020 daily exposure to PM2.5 and O3 on a census tract level. I aggregated the census tract data to ZIP Code using a spatial weighting approach and estimated short-term air pollution as a 7-day average of daily PM2.5 and O3 exposure prior to patient hospitalization.

For the first aim, the systematic review included 42 studies that examined the relationship between ambient air pollution, such as exposures to PM2.5, NO₂, and O₃, and individual-level adverse COVID-19, such as hospitalization, intensive care unit (ICU) admission, intensive respiratory support (IRS), and fatality. The studies were primarily retrospective cohort study designs, and were conducted in the United States and Europe (2020 to 2021). The majority of studies adjusted for cardiovascular morbidity without causal role specification, whereas some studies identified cardiovascular morbidity as a mediator or an effect modifier.

For the second aim, I found evidence of cardiovascular morbidity mediating the relationship between historical air pollution and risk of acute respiratory distress syndrome (ARDS), dialysis use, ventilation use, and COVID-19 fatality, but not risk of pneumonia from March to June 2020, within areas of greater hospital catchment. Indirect effects suggest that historical air pollution increases the risk of atrial fibrillation and myocardial infarction, which increases risk of adverse COVID-19.

For the third aim, I found evidence of synergistic interaction between short-term PM2.5 and presence of cardiovascular morbidities for only risk of COVID-19 pneumonia, in the latter half of 2020. Overall, there was evidence that cardiovascular morbidity mediates the relationship betweenhistorical air pollution and more severe COVID-19 outcomes, while cardiovascular morbidity synergistically interacts with short-term air pollution for risk of acute respiratory infections, such as pneumonia. This dissertation assesses the pathways by which air pollution may influence risk of adverse COVID-19, in better examining the causal role of cardiovascular morbidity. Knowledge gained could be used to mitigate population-level vulnerabilities to air pollution, and encourage population-level pandemic preparedness in the future.