key: cord-0789508-ayk0st36
authors: Mendy, Angelico; Wu, Xiao; Keller, Jason L.; Fassler, Cecily S.; Apewokin, Senu; Mersha, Tesfaye B.; Xie, Changchun; Pinney, Susan M.
title: Long-Term Exposure to Fine Particulate Matter and Hospitalization in COVID-19 Patients
date: 2021-01-26
journal: Respir Med
DOI: 10.1016/j.rmed.2021.106313
sha: e250408af188894a1aff638f9045450589596ecf
doc_id: 789508
cord_uid: ayk0st36

BACKGROUND: Ecological evidence suggests that exposure to air pollution affects coronavirus disease 2019 (COVID-19) outcomes. However, no individual-level study has confirmed the association to date. METHODS: We identified COVID-19 patients diagnosed at the University of Cincinnati hospitals and clinics and estimated particulate matter ≤2.5 μm (PM(2.5)) exposure over a 10-year period (2008-2017) at their residential zip codes. We used logistic regression to evaluate the association between PM(2.5) exposure and hospitalizations for COVID-19, adjusting for socioeconomic characteristics and comorbidities. RESULTS: Among the 1,128 patients included in our study, the mean (standard deviation) PM(2.5) was 11.34 (0.70) μg/m(3) for the 10-year average exposure and 13.83 (1.03) μg/m(3) for the 10-year maximal exposures. The association between long-term PM(2.5) exposure and hospitalization for COVID-19 was contingent upon having pre-existing asthma or chronic obstructive pulmonary (COPD) (P(interaction)=0.030 for average PM(2.5) and P(interaction)=0.001 for maximal PM(2.5)). In COVID-19 patients with asthma or COPD, the odds of hospitalization were 62% higher with 1 μg/m(3) increment in 10-year average PM(2.5) (odds ratio [OR]: 1.62, 95% confidence interval [CI]: 1.00-2.64) and 65% higher with 1 μg/m(3) increase in 10-year maximal PM(2.5) levels (OR: 1.65, 95% CI: 1.16-2.35). However, among COVID-19 patients without asthma or COPD, PM(2.5) exposure was not associated with higher hospitalizations (OR: 0.84, 95% CI: 0.65-1.09 for average PM(2.5) and OR: 0.78, 95% CI: 0.65-0.95 for maximal PM(2.5)). CONCLUSIONS: Long-term exposure to PM(2.5) is associated with higher odds of hospitalization in COVID-19 patients with pre-existing asthma or COPD.

Since its occurrence in China in December 2019, the coronavirus disease 2019 caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has rapidly spread into a pandemic and global health crisis by March 2020 [1] . Ecological studies suggest that exposure to ambient air pollutants such as fine particulate matter with an diameter ≤2.5 µm (PM 2.5 ), may contribute to COVID-19 severity and mortality [2, 3] . Possible mechanisms include impaired mucociliary clearance and increased susceptibility to infections as well as the exacerbation of existing respiratory and cardiovascular disease [2, 3] . However, these ecological studies correlating geographic rates of COVID-19 outcomes with geographic PM 2.5 levels suffer from ecological fallacy and require individual-level data for validation [4] . Therefore, we performed the first individual-level study on PM 2.5 exposure and hospitalizations for COVID-19.

We identified all COVID-19 patients diagnosed at the University of Cincinnati healthcare system (UC Health) between March 13, 2020 and July 5, 2020 using the electronic medical record system. UC Health consists of hospitals and clinics located in the greater Cincinnati metropolitan area which has a population of over 2 million people [1] . We identified 1,421 COVID-19 patients and after exclusion of 293 patients with missing data (225 for smoking, 65 for zip code, and 3 for sex), 1,128 participants were included in our study. The University of Cincinnati Institutional Review Board (IRB) exempted the study from IRB approval since it used a de-identified dataset stripped of all Health Insurance Portability and Accountability Act (HIPPAA) identifiers.

J o u r n a l P r e -p r o o f Hospitalization defined as admission for a duration of ≥24 hours to a hospital or clinic within the UC healthcare system for COVID-19 following the diagnosis of the infection. The delay between COVID-19 diagnosis and hospitalization was no more than a week and the diagnosis of COVID-19 was again confirmed at admission to the hospital.

PM 2.5 exposure was estimated on a 0.01°×0.01° grid using a validated exposure prediction model merging satellite, modeled, and monitored PM 2.5 data [5] . Zonal statistics were used to aggregate PM 2.5 exposure estimates at the patients' residential zip codes over the 10year period from 2008 to 2017.

Sociodemographic characteristics such as age at COVID-19 diagnosis, sex, race/ethnicity, and smoking were self-reported. The median household income at residential zip code was estimated using 2018 income statistics from the Census Bureau [6] . Comorbidities were defined using the 10 th revision of the International Classification of Diseases (ICD10) codes. They included obesity (E66), diabetes (E11), asthma (J45), chronic obstructive pulmonary disease (COPD) (J44), chronic kidney disease (N18), cardiovascular disease (I00-I99), and neoplasm or history of neoplasm (C00-D49).

Descriptive analyses were performed and logistic regression was used to estimate the odds ratios (OR) and corresponding 95% confidence intervals (CI) for hospitalization associated with 1 µg/m 3 increase in average and maximal PM 2.5 concentrations. The models were adjusted for age and median household income used as continuous variables as well as sex, J o u r n a l P r e -p r o o f race/ethnicity, cigarette smoking, and comorbidities (obesity, diabetes, asthma, COPD, cardiovascular disease, chronic kidney disease, and neoplasm or history of neoplasm) used as categorical variables. To identify subgroups of patients vulnerable to COVID-19 hospitalization in relation to PM 2.5 exposure, we tested each covariate for effect modification with a multiplicative interaction term included in the model one at a time and calculated the interaction P-values (P interaction ). The analyses were performed using SAS Version 9.4 (SAS Institute, Cary, NC) and p-values <0.05 were considered statistically significant.

The 1,128 patients included in our study had median age of 46 years (interquartile range: 32 to 62 years). They were mostly residents of Ohio (96.6%) and the remaining 3.4% Table 1 , PM 2.5 levels were higher in women, in non-Hispanic Blacks, in participants with a median household income below $50,000, and in patients with diabetes, asthma, or COPD.

In logistic regression analysis adjusted for covariates, the association of long-term exposure to PM 2.5 with COVID-19 hospitalization was contingent upon the presence of a preexisting respiratory disease (i.e. asthma or COPD) (P interaction =0.030 for average PM 2.5 and J o u r n a l P r e -p r o o f P interaction =0.001 for maximal PM 2.5 ). In COVID-19 patients with respiratory disease, the odds of hospitalization were increased by 62% with 1 µg/m 3 (Figure 1 ).

In analysis stratified by asthma and COPD, the odds hospitalization for COVID-19 associated with 1 µg/m 3 of maximal PM 2.5 was 82% higher in patients with asthma (OR: 1.82, 95% CI: 1.13-2.93) (169 COVID-19 patients, including 55 hospitalized) (P interaction =0.008 for effect modification by asthma) and 65% higher in those with COPD (OR: 1.65, 95% CI: 1.05-2.60) (107 COVID-19 patients, including 57 hospitalized) (P interaction =0.017 for effect modification by COPD) (Figure 1) . PM 2.5 association with COVID-19 hospitalization did not differ by the other covariate.

The unadjusted estimates for the association between exposure to PM 2.5 and COVID-19 hospitalization overall and by pre-existing respiratory disease are reported in Supplementary   Tables 1 

This is the first individual-level study on PM 2.5 and COVID-19 outcomes. The results suggest that long-term exposure to PM 2.5 is associated with higher odds of hospitalization in COVID-19 patients with pre-existing asthma or COPD.

These results are consistent with reports that PM 2.5 exposure may exacerbate asthma and COPD by causing airway inflammation through the release of proinflammatory cytokines and free radicals from activated alveolar macrophages [3, 7, 8] . In addition to causing airway oxidative stress and mucosal damage, PM 2.5 can impair mucociliary clearance of pathogens and natural killer cell response and increase susceptibility to COVID-19 and COVID-19 severity [3, 7, 8] . The reason for the inverse association between maximal PM 2.5 and hospitalization in COVID-19 patients without respiratory disease is unclear and should be further investigated. It is possible that in this population, healthier patients who had lower risk of COVID-19 hospitalization tended to live in areas of higher PM 2.5 exposure or that we were unable to account for unmeasured potential confounders. Limitations of our study include the estimation of PM 2.5 exposure at the residential zip-code level and from 2008 to 2017 since data for more precise locations and for the years 2018 and 2019 was not available. However, if exposure misclassification exists from estimating PM 2.5 exposure at the zip-code level, it is expected to be non-differential, attenuating the associations [9] .

In conclusion, long-term exposure to PM 2.5 was associated with higher odds of hospitalization in COVID-19 patients with pre-existing asthma or COPD. Independent 12 *P < 0.05 **P < 0.01 Figure 1 : Odds ratios (OR) and 95% confidence interval (CI) for association of 1µ µ µ µg/m 3 increase in average and maximal PM 2.5 exposure with COVID-19 hospitalization In Panels A and B, OR (95% CI) reported for 1µg/m 3 increase in average (panel A) and maximal (panel B) PM 2.5 in all participants and in participants with and without respiratory disease. In Panels C and D, OR (95% CI) reported for 1µg/m 3 increase in average (panel C) and maximal (panel D) PM 2.5 in participants with and without asthma or with and without COPD. PM 2.5 association with COVID-19 hospitalization was different by respiratory disease for average PM 2.5 (panel A) and for maximal PM 2.5 (panels B and D). Models adjusted for age, sex, race/ethnicity, median household income, cigarette smoking, and comorbidities (obesity, diabetes, asthma, COPD, cardiovascular disease, chronic kidney disease, and neoplasm or history of neoplasm) J o u r n a l P r e -p r o o f

Factors associated with hospitalization and disease severity in a racially and ethnically diverse population of COVID-19 patients. medRxiv

Air pollution and COVID-19 mortality in the United States: Strengths and limitations of an ecological regression analysis

Air pollution, racial disparities, and COVID-19 mortality

The ecological fallacy strikes back

Regional estimates of chemical composition of fine particulate matter using a combined geoscience-statistical method with information from satellites, models, and monitors

US census bureau, current population reports. income and poverty in the United States

Synergistic association of house endotoxin exposure and ambient air pollution with asthma outcomes

Motor vehicle air pollution and asthma in children: A meta-analysis

Exposure measurement error in PM 2.5 health effects studies: a pooled analysis of eight personal exposure validation studies

The authors would like to acknowledge Matthew Benjamin Sabath for his assistance in the PM 2.5 data collection.J o u r n a l P r e -p r o o f