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An external exposome-wide association study of COVID-19 mortality in the United States.

ABSTRACT: The risk factors for severe COVID-19 beyond older age and certain underlying health conditions are largely unknown. Recent studies suggested that long-term environmental exposures may be important determinants of severe COVID-19. However, very few environmental factors have been studied, often separately, without considering the totality of the external environment (i.e., the external exposome). We conducted an external exposome-wide association study (ExWAS) using the nationwide county-level COVID-19 mortality data in the contiguous US. A total of 337 variables characterizing the external exposome from 8 data sources were integrated, harmonized, and spatiotemporally linked to each county. A two-phase procedure was used: (1) in Phase 1, a random 50:50 split divided the data into a discovery set and a replication set, and associations between COVID-19 mortality and individual factors were examined using mixed-effect negative binomial regression models, with multiple comparisons addressed, and (2) in Phase 2, a multivariable regression model including all variables that are significant from both the discovery and replication sets in Phase 1 was fitted. A total of 13 and 22 variables were significant in the discovery and replication sets in Phase 1, respectively. All the 4 variables that were significant in both sets in Phase 1 remained statistically significant in Phase 2, including two air toxicants (i.e., nitrogen dioxide or NO₂, and benzidine), one vacant land measure, and one food environment measure. This is the first external exposome study of COVID-19 mortality. It confirmed some of the previously reported environmental factors associated with COVID-19 mortality, but also generated unexpected predictors that may warrant more focused evaluation.

SUBMITTER: Hu H

PROVIDER: S-EPMC7788319 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:It is widely recognized that exogenous factors play an important role in the development of hypertensive disorders of pregnancy (HDP). However, only a few external environmental factors have been studied, often separately, with no attempt to examine the totality of the external environment, or the external exposome. We conducted an external exposome-wide association study (ExWAS) using the Florida Vital Statistics Birth Records including 819,399 women with live births in 2010-2013. A total of 5784 factors characterizing women's surrounding natural, built, and social environment during pregnancy from 10 data sources were collected, harmonized, integrated, and spatiotemporally linked to the women based on pregnancy periods using 250 m buffers around their geocoded residential addresses. A random 50:50 split divided the data into discovery and replication sets, and a 3-phase procedure was used. In phase 1, associations between HDP and individual factors were examined, and Bonferroni adjustment was performed. In phase 2, an elastic net model was used to perform variable selection among significant variables from phase 1. In phase 3, a multivariable logistic regression model including all variables selected by the elastic net model was fitted. Variables that were significant in both the discovery and replication sets were retained. Among the 528 and 490 variables identified in Phase 1, 232 and 224 were selected by the elastic net model in Phase 2, and 67 and 48 variables remained statistically significant in Phase 3 in the discovery and replication sets, respectively. A total of 12 variables were significant in both the discovery and replication sets, including air toxicants (e.g., 2,2,4-trimethylpentane), meteorological factors (e.g., omega or vertical velocity at 125mb pressure level), neighborhood crime and safety (e.g., burglary rate), and neighborhood sociodemographic status (e.g., urbanization). This is the first large external exposome study of HDP. It confirmed some of the previously reported associations and generated unexpected predictors within the environment that may warrant more focused evaluation.

Project description:BackgroundFully assessing the mortality burden of the COVID-19 pandemic requires measuring years of life lost (YLLs) and accounting for quality-of-life differences.ObjectiveTo measure YLLs and quality-adjusted life-years (QALYs) lost from the COVID-19 pandemic, by age, sex, race/ethnicity, and comorbidity.DesignState-transition microsimulation model.Data sourcesHealth and Retirement Study, Panel Study of Income Dynamics, data on excess deaths from the Centers for Disease Control and Prevention, and nursing home death counts from the Centers for Medicare & Medicaid Services.Target populationU.S. population aged 25 years and older.Time horizonLifetime.PerspectiveIndividual.InterventionCOVID-19 pandemic through 13 March 2021.Outcome measuresYLLs and QALYs lost per 10 000 persons in the population. The estimates account for the age, sex, and race/ethnicity of decedents, along with obesity, smoking behavior, lung disease, heart disease, diabetes, cancer, stroke, hypertension, dementia, and nursing home residence.Results of base-case analysisThe COVID-19 pandemic resulted in 6.62 million QALYs lost (9.08 million YLLs) through 13 March 2021, with 3.6 million (54%) lost by those aged 25 to 64 years. The greatest toll was on Black and Hispanic communities, especially among men aged 65 years or older, who lost 1138 and 1371 QALYs, respectively, per 10 000 persons. Absent the pandemic, 38% of decedents would have had average or above-average life expectancies for their subgroup defined by age, sex, and race/ethnicity.Results of sensitivity analysisAccounting for uncertainty in risk factors for death from COVID-19 yielded similar results.LimitationEstimates may vary depending on assumptions about mortality and quality-of-life projections.ConclusionBeyond excess deaths alone, the COVID-19 pandemic imposed a greater life expectancy burden on persons aged 25 to 64 years, including those with average or above-average life expectancies, and a disproportionate burden on Black and Hispanic communities.Primary funding sourceNational Institute on Aging.

Project description:ImportanceSARS-CoV-2, which causes COVID-19, poses considerable morbidity and mortality risks. Studies using data collected during routine clinical practice can supplement randomized clinical trials to provide needed evidence, especially during a global pandemic, and can yield markedly larger sample sizes to assess outcomes for important patient subgroups.ObjectiveTo evaluate the association of remdesivir treatment with inpatient mortality among patients with COVID-19 outside of the clinical trial setting.Design, setting, and participantsA retrospective cohort study in US hospitals using health insurance claims data linked to hospital chargemaster data from December 1, 2018, to May 3, 2021, was conducted among 24 856 adults hospitalized between May 1, 2020, and May 3, 2021, with newly diagnosed COVID-19 who received remdesivir and 24 856 propensity score-matched control patients.ExposureRemdesivir treatment.Main outcomes and measuresAll-cause inpatient mortality within 28 days of the start of remdesivir treatment for the remdesivir-exposed group or the matched index date for the control group.ResultsA total of 24 856 remdesivir-exposed patients (12 596 men [50.7%]; mean [SD] age, 66.8 [15.4] years) and 24 856 propensity score-matched control patients (12 621 men [50.8%]; mean [SD] age, 66.8 [15.4] years) were included in the study. Median follow-up was 6 days (IQR, 4-11 days) in the remdesivir group and 5 days (IQR, 2-10 days) in the control group. There were 3557 mortality events (14.3%) in the remdesivir group and 3775 mortality events (15.2%) in the control group. The 28-day mortality rate was 0.5 per person-month in the remdesivir group and 0.6 per person-month in the control group. Remdesivir treatment was associated with a statistically significant 17% reduction in inpatient mortality among patients hospitalized with COVID-19 compared with propensity score-matched control patients (hazard ratio, 0.83 [95% CI, 0.79-0.87]).Conclusions and relevanceIn this retrospective cohort study using health insurance claims and hospital chargemaster data, remdesivir treatment was associated with a significantly reduced inpatient mortality overall among patients hospitalized with COVID-19. Results of this analysis using data collected during routine clinical practice and state-of-the-art methods complement results from randomized clinical trials. Future areas of research include assessing the association of remdesivir treatment with inpatient mortality during the circulation of different variants and relative to time from symptom onset.