key: cord-0816062-gw38qh8q authors: Liu, Samuel; Li, Meng title: Ambient air pollutants and their effect on COVID-19 mortality in the United States of America date: 2020-11-20 journal: Rev Panam Salud Publica DOI: 10.26633/rpsp.2020.159 sha: 0fd7f2f937482bbf209676cbc307fd828313053e doc_id: 816062 cord_uid: gw38qh8q OBJECTIVE. To examine the impact of four ambient air pollutants on the COVID-19 mortality rate in the United States of America. METHODS. Using publicly accessible data collected by the United States Census Bureau, Environmental Protection Agency, and other agencies, county-level mortality rates were regressed on concentration values of ground-level ozone, nitrogen dioxide, carbon monoxide, and sulfur dioxide. Four confounder variables were included in the regression analysis: median household income, rate of hospital beds, population density, and days since first confirmed case. RESULTS. Regression analysis showed that ground-level ozone is positively correlated with county-level mortality rates regardless of whether confounders are controlled for. Nitrogen dioxide is also shown to have a direct relationship with county-level mortality rates, except when all confounders are included in the analysis. CONCLUSIONS. High ground-level ozone and nitrogen dioxide concentrations contribute to a greater COVID-19 mortality rate. To limit further losses, it is important to reflect research findings in public policies. In the case of air pollution, environmental restrictions should be reinforced, and extra precautions should be taken as facilities start reopening. The 2019 novel coronavirus (SARS-CoV-2) has negatively impacted a great number of people physically, mentally, and economically. First reported in early December in Wuhan, China, COVID-19 is a respiratory disease with flu-like symptoms and pneumonia. Given its incubation period and modes of transmission, the virus is highly infectious and spread quickly globally, claiming many lives. As of 27 May 2020, the death toll in the United States of America had reached 100 000 (1) . Globally, studies have proved that COVID-19 is more lethal among certain groups, for instance, adults aged ≥65 years and people with underlying respiratory and cardiovascular health conditions (2) . It is crucial to investigate the variables that influence COVID-19 deaths, in order to prevent the mortality rate from increasing. This study aims to evaluate a possible correlation between COVID-19 mortality and four ambient air pollutants. The five major tropospheric air pollutants are ground-level ozone (O 3 ), nitrogen dioxide (NO 2 ), carbon monoxide (CO), sulfur dioxide (SO 2 ), and particulate matter 2.5 microns or less in diameter (PM 2.5 ). All these pollutants are known to be associated with adverse and sometimes fatal effects on health, including lung cancer, stroke, and cardiovascular disease (3) . For example, NO 2 is detrimental to human health by damaging lung linings and stimulating other acute respiratory illnesses (4) . Ground-level ozone also damages cells and airway lining fluid, inducing immune-inflammatory responses in the lungs and the cardiovascular system (5) . Essentially, air pollution dysregulates antiviral immune responses and exacerbates respiratory and cardiovascular conditions (6) . Since these pollution-induced health conditions are the very same conditions that increase the likelihood of COVID-19 death, it is reasonable to hypothesize that higher ambient air pollutant concentrations are associated with higher COVID-19 mortality rates. A study by Wu et al. proved a positive correlation between COVID-19 mortality rates and long-term PM 2.5 exposure using (USDA ERS) website 4 and used their latest 2018 median household income in dollars. The rate of hospital beds is the number of hospital beds per county adjusted for county population. Hospital bed data were obtained from Homeland Infrastructure Foundation-Level Data Geoplatform (HIFLD Open Data). 5 For the population density variable, we divided the county's total 2019 population estimate by its area in square miles, both data being obtained from the U.S. Census Bureau website. 3 For the days since first confirmed case variable, we obtained data from the USAFacts website, 2 which aggregates data from the CDC and reference state and local agencies. For this variable, we set the final date of reported confirmed COVID-19 cases to be 14 May 2020 to ensure consistency with our calculation of mortality rates. All data used in this study are publicly available for further investigation and verification of our results. The descriptive statistics for all of the above variables are presented in Table 1 . It is important to note that although the United States has a total of 3 141 counties including the District of Columbia, only 2 522 counties (80.29%) have complete data for all four confounders, because the rate of hospital beds data source (HIFLD) excludes counties without intensive care hospital beds. The varying number of county observations for each of the four pollutants was due to the fact that the EPA only collects pollutants data for selected counties that validly represent certain regions of the United States, and the counties reported vary for each of the four pollutants. Pearson correlation tests were conducted among all variables except mortality rate for the datasets containing each of the four pollutants. Correlation matrices are presented in Table 2 . Using R statistical software, we regressed mortality rate on O 3 , NO 2 , CO, and SO 2 concentrations using the following model: Y (Mortality rate ) = α + β 1 X 1 (Pollutant concentration) + β 2 X 2 (Median household income) + β 3 X 3 (Rate of hospital beds) + β 4 X 4 (Population density) + β 5 X 5 (Days since first case) This model was run for the dataset containing each pollutant separately, with X 1 representing O 3 , NO 2 , CO, and SO 2 concentrations, respectively. Table 3 summarizes the regression results with all confounders included in the model. Out of the four air pollutants, only ground level ozone (O 3 ) shows a significant and positive correlation with COVID-19 United States county-level data, showing that an increase of 1 μg/m 3 in PM 2.5 is associated with an 8% increase in the COVID-19 mortality rate (7) . Recent studies evaluating the correlation of NO 2 and mortality rates in northern Italy (8) and regions of England (9) also showed a direct relationship. Surprisingly, a study analyzing ground-level ozone levels in regions of England found an inverse relationship between ozone and COVID-19 mortality rates (9) . The authors argued that the unexpected relationship might have been caused by the conversion of ozone into secondary hazardous gaseous species. Therefore, lower levels of ozone could be linked to higher levels of ozone oxidation products, and subsequently a higher COVID-19 mortality rate. Besides the study on PM 2.5 by Wu et al., there has not been any study evaluating the effect of the other four main air pollutants on mortality rates in the United States. This paper fills the gap by exploring the relationship between U.S. Environmental Protection Agency (EPA) county-level design values of O 3 , NO 2 , CO, and SO 2 with the county-level COVID-19 mortality rate. We obtained county-level air pollutant design values for O 3 , NO 2 , CO, and SO 2 from the EPA website. 1 For mortality rates, we obtained the number of COVID-19 deaths from the USAFacts website, 2 which aggregates data from the U.S. Centers for Disease Control and Prevention (CDC) and reference state and local agencies, and expressed each county's total COVID-19 deaths up until 14 May 2020 as a percentage of the county's total 2019 population estimate, as obtained from the U.S. Census Bureau website. 3 We included multiple confounder variables in our linear regression analysis. From the 20 county-level variables evaluated by Wu et al., we selected the four variables that showed significance in their analysis: median household income, rate of hospital beds, population density, and days since first confirmed case. We obtained median household income data from the U.S. Department of Agriculture's Economic Research Service mortality rates, with an increase of 1 ppm in ozone concentration associated with an increase of 0.382% in mortality rate. To account for collinearity between independent variables, confounders that show significant correlation from the Table 2 matrices were excluded from the regression analysis. The regression analysis results are presented in Table 4 . With correlated variables excluded, both O 3 and NO 2 concentrations show significant relationships with COVID-19 mortality rate. Specifically, when concentrations of O 3 increase by 1 ppm, the mortality rate increases by 0.857%. When concentrations of NO 2 increase by 1 ppb, the mortality rate increases by 0.002%. This finding for NO 2 is consistent with studies conducted in northern Italy (8) and London (9) , which also found a positive relationship between NO 2 and increased risk of COVID-19 death. The regression results for CO and SO 2 remain insignificant, suggesting no impact on COVID-19 mortality rate. As a robustness test, an unadjusted regression analysis was conducted to evaluate the relationship between pollutant concentrations and mortality rate. These results are presented in Table 5 . Excluding all confounders, both O 3 and NO 2 concentrations still show significant relationships with COVID-19 mortality rate. When concentrations of O 3 increase by 1 ppm, the mortality rate increases by 0.836%. When concentrations of NO 2 increase by 1 ppb, the mortality rate increases by 0.002%. It is important to note that ground-level ozone and stratospheric ozone are very different in their effects and formation. While stratospheric ozone makes up the ozone layer that blocks out harmful ultraviolet radiation from the sun and is formed from natural chemical processes, ground-level ozone is a constituent of smog and is formed from nitrogen oxides (NO x ) commonly emitted into the atmosphere through manmade processes such as industrial emissions and motor vehicle exhaust. Given that NO 2 is a form of nitrogen oxide (NO x ), it explains the dual significance of the impact of O 3 and NO 2 on the COVID-19 mortality rate. Multiple studies conducted on ground-level ozone have described its direct association with negative respiratory and cardiovascular health outcomes. In China, where high levels of smog have created hazardous living conditions, an estimated 230 000 to 403 000 respiratory-related deaths were attributable to long-term O 3 exposure in 2016 (10) . The preexisting adverse health effects caused by exposure to O 3 render individuals more susceptible to COVID-19-related death, due to weakened respiratory, cardiovascular, and immune functions. This relationship was discovered during the 2002 SARS outbreak, in which a study showed that SARS patients from Chinese regions with moderate air pollution index (API, in which ozone is included) had an 84% increased risk of dying than those from regions with low APIs (11) . With the recent mandated lockdowns and stay-at-home orders, there has been a global improvement in air quality due to the temporary closure of factories and the decrease in vehicle usage. Despite the reduction in NO x and PM (12) . As countries such as the United States reopen, pollution levels will slowly start to return to pre-COVID-19 levels. Despite a semi-centennial shift toward a cleaner atmosphere and greener alternatives, air pollutants still play a large role in causing adverse health effects, and stricter measures must be taken to limit emissions. Ozone has been overlooked when it comes to regulation. In the United States in 2016, 90% of noncompliance to the national ambient air quality standards was in relation to ozone, whereas only 10% was in relation to particulate matter and other pollutants (5) . The COVID-19 pandemic only more clearly highlights the significant and detrimental outcomes of air pollution, which has been a looming problem for decades. Very recently, to combat the economic crisis, United States air pollutant restrictions are being eased to allow recovery and incentivize production. It is extremely difficult to balance economic vitality with COVID-19 casualties, but taking preventive measures by further limiting pollution may be more economically and socially effective in the long run. A recent study by Wang et al. estimated that if drastic measures are taken to reduce greenhouse gas emissions and air pollution in California, there will be a projected 14 000 premature deaths prevented in the state in 2050, as well as reduced respiratory and cardiovascular related hospital visits (13) . By adopting measures such as implementing more green energy alternatives and incentives for electric vehicle ownership, ground-level ozone can be significantly reduced alongside other pollutants. This study provides empirical evidence that ground-level ozone is positively correlated with COVID-19 mortality rate, regardless of whether the confounders are controlled for. NO 2 is also significantly correlated with the COVID-19 mortality rate except when all confounders are included in the regression analysis. This study was subject to multiple limitations that could result in inaccuracies. There are still other confounder variables that were not accounted for, such as racial demographic, education level, and days since stay-at-home order. The sample size was also small, as the number of county-level observations extracted from the EPA public data was a fraction of the United States' total 3 141 counties. Within this limited number of counties there were outliers that resulted from the geographic and demographic diversity, ranging from extremely densely populated hotspot counties to isolated and sparsely populated counties. Given these and other limitations, further study and research on the correlation of air pollution and COVID-19 should be conducted to bring about a thorough understanding of this novel virus, as a possible second wave is on the horizon. Author contributions. SL computed and analyzed data and wrote the paper. ML assisted, provided guidance, and edited the paper. Both authors reviewed and approved the final version. 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Authors hold sole responsibility for the views expressed in the manuscript, which may not necessarily reflect the opinion or policy of the RPSP/PAJPH and/or PAHO. Objetivo. Examinar el impacto de cuatro contaminantes del aire ambiental en la tasa de mortalidad por la COVID-19 en los Estados Unidos de América. Métodos. Utilizando datos de acceso público recopilados por la Oficina del Censo de los Estados Unidos, la Agencia para la Protección del Medio Ambiente y otros organismos, se llevó a cabo análisis de regresión para evaluar la relación entre las concentraciones de ozono, dióxido de nitrógeno, monóxido de carbono y dióxido de azufre a nivel del suelo y las tasas de mortalidad a nivel de condado. En el análisis de regresión se incluyeron cuatro variables confusoras: la mediana de los ingresos familiares, la tasa de camas de hospital, la densidad de población y los días transcurridos desde el primer caso confirmado. Resultados. El análisis de regresión mostró que el ozono a nivel del suelo se correlaciona de manera positiva con las tasas de mortalidad a nivel de condado, independientemente de si los factores de confusión están controlados. El dióxido de nitrógeno también tiene una relación directa con las tasas de mortalidad a nivel de condado, excepto cuando se incluyen todos los factores de confusión en el análisis. Conclusiones. Las concentraciones elevadas de ozono y dióxido de nitrógeno a nivel del suelo contribuyen a una mayor tasa de mortalidad por COVID-19. Para limitar los daños, es importante que los resultados de investigación se reflejen en las políticas públicas. En el caso de la contaminación del aire ambiental, deben reforzarse las restricciones ambientales y deben tomarse precauciones adicionales cuando los establecimientos empiecen a reabrirse. Infecciones por coronavirus; contaminación del aire; mortalidad; ozono; dióxido de nitrógeno; Estados Unidos.