Gene-Environment Interaction Analysis Incorporating Sex, Cardiometabolic Diseases, and Multiple Deprivation Index Reveals Novel Genetic Associations With COVID-19 Severity

Increasing evidence indicates that specific genetic variants influence the severity of outcomes after infection with COVID-19. However, it is not clear whether the effect of these genetic factors is independent of the risk due to more established non-genetic demographic and metabolic risk factors such as male sex, poor cardiometabolic health, and low socioeconomic status. We sought to identify interactions between genetic variants and non-genetic risk factors influencing COVID-19 severity via a genome-wide interaction study in the UK Biobank. Of 378,051 unrelated individuals of European ancestry, 2,402 were classified as having experienced severe COVID-19, defined as hospitalization or death due to COVID-19. Exposures included sex, cardiometabolic risk factors [obesity and type 2 diabetes (T2D), tested jointly], and multiple deprivation index. Multiplicative interaction was tested using a logistic regression model, conducting both an interaction test and a joint test of genetic main and interaction effects. Five independent variants reached genome-wide significance in the joint test, one of which also reached significance in the interaction test. One of these, rs2268616 in the placental growth factor (PGF) gene, showed stronger effects in males and in individuals with T2D. None of the five variants showed effects on a similarly-defined phenotype in a lookup in the COVID-19 Host Genetics Initiative. These results reveal potential additional genetic loci contributing to COVID-19 severity and demonstrate the value of including non-genetic risk factors in an interaction testing approach for genetic discovery.

Community versus individual risk of SARS-CoV-2 infection in two municipalities of Louisiana, USA: An assessment of Area Deprivation Index (ADI) paired with seroprevalence data over time

Objective Determine whether an individual is at greater risk of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) infection because of their community or their individual risk factors. Study design and setting 4,752 records from two large prevalence studies in New Orleans and Baton Rouge, Louisiana were used to assess whether zip code tabulation areas (ZCTA)-level area deprivation index (ADI) or individual factors accounted for risk of infection. Logistic regression models assessed associations of individual-level demographic and socioeconomic factors and the zip code-level ADI with SARS-CoV-2 infection. Results In the unadjusted model, there were increased odds of infection among participants residing in high versus low ADI (both cities) and high versus mid-level ADI (Baton Rouge only) zip codes. When individual-level covariates were included, the odds of infection remained higher only among Baton Rouge participants who resided in high versus mid-level ADI ZCTAs. Several individual factors contributed to infection risk. After adjustment for ADI, race and age (Baton Rouge) and race, marital status, household size, and comorbidities (New Orleans) were significant. Conclusions While higher ADI was associated with higher risk of SARS-CoV-2 infection, individual-level participant characteristics accounted for a significant proportion of this association. Additionally, stage of the pandemic may affect individual risk factors for infection.

Greenspace availability or greenspace usability, which matters on PM2.5-related premature deaths: evidence from 360 cities in China

Greenspace exposure is confirmed to reduce air pollution-related negative health impact. However, which type of greenspace exposure matters more on mitigating air pollution-related deaths and whether this effect is regionally different remain unclear. Here we show, greenspace usability exposure plays a more significant role in mitigating PM2.5-related premature deaths in 360 China cities generally speaking. By clustering 360 cities into urban-rural and Deprivation Index groups, we further find that greenspace availability and usability together work on respiratory health in rural regions, and greenspace availability matters more in very low deprived areas or urban and rural regions. Our results that increasing greenspace usability exposure is more helpful in reducing air pollution-related premature deaths may inform more effective and equitable greenspace planning policies in rapidly developing countries like China.

Abstract 1122‐000159: Area Deprivation Index and Transfer Likelihood Offer Insight into Improving Stroke Care Access Equity

Introduction : Time is brain for stroke care. Socioeconomic disparities may have an impact on timely access to stroke care. A well known factor that affects access to thrombectomy is the necessity for transfer from a non‐thrombectomy capable center to a thrombectomy capable center (TSC). The Area Deprivation Index (ADI) is a validated, neighborhood‐level composite measure (scored 1–100) which uses income, education, employment, housing quality, and other factors to identify geographic areas with increased need. We analyzed the association between ADI and requirement of transfer prior to thrombectomy to further understand how establishment of TSCs in areas with higher ADI and severity score bypass protocols can increase access to stroke care across all ranges of socioeconomic need. Methods : We obtained transfer status and the duration of the transfer time for all thrombectomy patients treated between 2016 and 2021 in a large, urban multi‐hospital health system and matched them with their respective census‐tract level ADI scores from Neighborhood Atlas, with a higher ADI score signifying lower socioeconomic status. Preliminary analysis utilized logistic regression to compare the ADI between transfer and non‐transfer cases. Further exploration observed temporal changes to the percentage of patients requiring transfer across 4 ADI ranges. Results : Among 513 cases for which we had a pick up address for between 2016–2021, the average ADI of pick‐up locations was 10.3 (range: 1 ‐ 70.5). ADI was significantly predictive of transfer status (p = 0.0004), with a 1 unit increase in ADI increasing the odds of being transferred by 1.035. Patients requiring transfer took an average of 2.7 hours longer to thrombectomy compared to non‐transfer patients. However, within the transfer population, a higher ADI did not correlate with increased transfer time. Across all ADI ranges, the likelihood of transfer began to decrease in 2018. This is likely due to the establishment of a new TSC in 2018 as well as the implementation of an EMS triage protocol transporting patients with a higher severity of stroke directly to TSCs. Notably, patients in the highest ADI range did not experience decreased likelihood of transfer until 2020, correlating with establishment of another TSC. Conclusions : Across urban census tracts, patients with a higher ADI had an increased likelihood of transfer, and hence delay in access to thrombectomy. Equity to access to thrombectomy improved over time. Expanding thrombectomy access as well as establishing EMS triage protocols appear to correlate with improvement in access to stroke thrombectomy care for patients with higher ADI.

Associations between Neighborhood Deprivation Index, Parent Perceptions and Preschooler Lifestyle Behaviors

Parental perceptions and use of neighborhood facilities are important factors that are related to children’s dietary intake and physical activity. The aim of this study was to examine the association between neighborhood deprivation index, parents’ perceptions of their neighborhood environment, and healthy/unhealthy markers of child dietary intake, physical activity, and TV screen time. This cross-sectional study was conducted in Dublin, Ireland. The lifestyle behaviors among children and parental perceptions of their neighborhood environment were reported by the parents of 276 children aged 3–5 years by using parent-completed questionnaires. Deprivation index was assessed using the geographic information system (GIS). Data were analyzed using binary logistic regression, adjusting for socio-demographic confounders. In adjusted models, high deprivation index was associated with parental perception of the neighborhood as unsafe for walking and cycling due to crime (OR 1.59, 95% CI 1.04–2.43, p = 0.031) and children’s low engagement in structured physical activity (OR 0.35, 95% CI 0.17–0.72, p = 0.004). Parental perceptions of an unsafe neighborhood due to heavy traffic were negatively correlated with children’s active play (OR 0.73, 95% CI 0.55–0.95, p = 0.022). Children whose parents reported high satisfaction with the number of local sit-in and takeaway restaurants were 41% more likely to consume confectionary/sugar sweetened beverages (SSBs) weekly. In this age group, parents play an important role in children’s lifestyle behaviors; therefore, a better understanding of parents’ perceptions and their use of neighborhood facilities could contribute to creating a healthy environment for this age group.

Racial, Socioeconomic, and Demographic Disparities in the Management of Meniscal Tears (179)

Objectives: Meniscal surgery, repair or debridement, makes up about a third of all arthroscopic related surgery. In the adult population, there is much debate about which patients should undergo surgical intervention and which should be treated nonoperatively. There seems to be a paucity of literature related to how a patient’s demographics, insurance status, socioeconomic status, and race impact the likelihood of undergoing surgical intervention. In the present study, we sought to determine how these factors influence whether a patient undergoes surgical intervention following a meniscal injury. Methods: From 2009-2018, claims for adult (≥18 years of age) patients who were diagnosed with a primary meniscus injury were identified in the New York Statewide Planning and Research Cooperative System (SPARCS) database. SPARCS is a comprehensive all-payer database collecting all inpatient and outpatient pre-adjudicated claims in New York. ICD 9/10 CM codes were used to identify the initial diagnosis for each patient. ICD9/10 PCS and Current Procedural Terminology (CPT) codes were used to identify subsequent meniscus surgery. The procedures identified were linked with the initial diagnosis and patients were noted as either having meniscus surgery, or not having meniscus surgery. After missing data was removed, logistic regression analysis was performed to determine the effect of patient factors on the likelihood of having surgery after a diagnosis of meniscus injury. Results: Of 394,007 adult meniscus injury diagnoses, 84.7% proceeded to undergo surgical intervention. The median age for no surgery was 51 (mean: 49.4) and the median age for surgery was 52 (mean: 50.2) (p<.0001) (Table 1). Females relative to males (OR=0.757, p<.0001), increased social deprivation index (SDI) (OR=0.994, p<.0001), African American compared to white race (OR=0.822, p<.0001), hispanic relative to non-hispanic ethnicity (OR=0.682, p<.0001), federal relative to private insurance (OR=0.459, p<.0001), and self-pay relative to private insurance (OR=0.437, p<.0001) were all associated with decreased odds of undergoing meniscus surgery. Older patients (OR=1.009, p<.0001), worker’s compensation relative to private insurance (OR=1.284, p<.0001) and patients with a charlson comorbidity index (CCI) score ≥1 had increased odds of undergoing surgery (OR=1.129, p<.0001) (Table 2). Conclusions: Multiple demographic, insurance status, socioeconomic status, and race factors influence the decision to manage meniscal tears surgically. Females, those with increased social deprivation index, African-Americans, Hispanics, or those with federal insurance or self-pay (when compared to private insurance) were less likely to undergo surgical intervention for meniscal tears. Those with workers’ compensation, who were of older age and higher CCI were more likely to undergo surgical intervention. Further research is ultimately needed to elicit causes for disparities between demographic groups.