Putcha, Nirupama

ImportanceIdentifying factors associated with resilience during the COVID-19 pandemic can inform targeted interventions and resource allocation for groups disproportionately affected by systemic inequities.ObjectiveTo examine factors associated with self-reported resilience during the COVID-19 pandemic in racially and ethnically diverse, community-dwelling US adults.Design, Setting, and ParticipantsThis cross-sectional study was conducted as part of the Collaborative Cohort of Cohorts for COVID-19 Research (C4R) study, which assessed the associations of the pandemic with self-reported resilience of participants from 14 established US prospective cohorts since January 2021. This report includes participants who responded to the self-reported resilience question on C4R questionnaires. Data was initially analyzed from October 2023 to May 2024, with updated analyses performed from August 2024 to April 2025.ExposureRace and ethnicity, behavior factors, health conditions, and social determinants of health measurements accessed before and during the COVID-19 pandemic through cohort visits and C4R questionnaires.Main Outcomes and MeasuresSelf-reported resilience was collected via 1 question (from the Brief Resilience Scale) in C4R questionnaires, “I tend to bounce back quickly after hard times.” Participants who answered agree or strongly agree were classified as resilient, and those who reported neutral, disagree, or strongly disagree were classified as not resilient. Modified Poisson regression was performed to estimate prevalence ratios (PRs) and access multivariable-adjusted associations with resilience.ResultsOf 31 045 participants (18 672 [60%] women; 10 746 [34.6%] aged <65 years), 1185 (3.8%) identified as American Indian, 6728 (21.7%) as Black, 293 (0.9%) as East Asian, 6311 (20.3%) as Hispanic, 565 (1.8%) as South Asian, and 15 961 (51.3%) as White; a total of 23 103 participants (74.4%) self-identified as resilient. Compared with White participants, Black and Hispanic participants had higher prevalence of self-reported resilience (adjusted PR [aPR], 1.04; 95% CI, 1.02-1.06; aPR, 1.08; 95% CI, 1.06-1.11; respectively) and American Indian and East Asian participants had lower prevalence (aPR, 0.90; 95% CI, 0.86-0.94; aPR, 0.76; 95% CI, 0.68-0.84; respectively). Higher education, being married or living as married, higher income, and overweight were also associated with higher prevalence of resilience. Being female, having diabetes, and being unemployed were associated with lower prevalence of self-reported resilience. Compared with participants with public insurance only, participants with private insurance had higher prevalence of resilience (aPR, 1.07; 95% CI, 1.03-1.10). COVID-19 vaccination and infection statuses were not significantly associated with resilience. Modification analyses showed important racial and ethnic differences in how factors such as hypertension, marital status, and insurance status were associated with resilience.Conclusions and RelevanceIn this cross-sectional study of 31 045 adults, self-reported resilience varied by race, ethnicity, and sociodemographic factors. These findings highlight the complex interplay of individual and social factors in shaping the perception of resilience.

Abstract Rationale: Adverse social determinants of health (SDOH) are common in COPD and associated with increased mortality. However, cause-specific mortality is understudied. We evaluated associations of neighborhood-level SDOH with all-cause and cause-specific mortality among individuals with or at-risk for COPD. Methods: SPIROMICS is an ongoing, multi-center, longitudinal observational study of individuals across the US with current or former personal smoking histories (≥20 pack-years), with or without spirometrically-defined COPD. We established geocoded neighborhood-level SDOH at baseline using 2010 census tract data, including specifically, area deprivation index (ADI) (range 0-100, 100 = most disadvantaged), poverty level (percentage of households below the poverty line), poor food access (>1/3 of residents with no access to fresh food stores within 1 mile in urban areas and 10 miles in rural areas), and food desert (low income plus poor food access). We ascertained all-cause and cause-specific mortality through 12/31/2021 using the National Death Index. Using Cox proportional hazards models, we evaluated the risk of all-cause mortality for each SDOH. We utilized competing-risk regression models to evaluate the risk of cardiovascular, respiratory, COPD (a subset of respiratory), and neoplastic causes of death individually with each SDOH. Models were adjusted for demographics, smoking status, pack-years, BMI categories, coronary heart disease, FEV1% predicted and study site. Effect modification by lung function was assessed using multiplicative interactions between SDOH and FEV1% predicted. Results: Among 2977 participants, mean ADI was 40.1±27.8. Within a participant's neighborhood, on average 10.4±10.4% of households were below the poverty line, 933 (31.3%) had poor food access, and 220 (7.4%) resided in a food desert. During a median follow-up of 7.8 years (IQR 5.6-9.2), 744 (25.0%) participants died, most commonly from respiratory causes including COPD. Neither ADI nor neighborhood poverty level were associated with all-cause mortality or any specific cause of death (Table). Despite lack of associations between food access and mortality (Table), individuals residing in a food desert had elevated risks of all-cause (HR: 1.36 [95%CI: 1.03-1.79]) and cardiovascular (HR: 2.62 [95%CI: 1.5-4.35]) deaths. There was no significant effect modification by lung function. Conclusions: In a large cohort of individuals with personal smoking histories, with or without COPD, living in a food desert was associated with increased all-cause and cardiovascular mortality. However, neighborhood poverty level and food access, the two components of food desert, were not independently associated with mortality, suggesting the association of multimodal SDOH variables with mortality in this population.

Abstract Rationale: We have previously shown reduced total IgG, IgG subclasses, and levels/function of pneumococcal-specific antibodies are associated with increased risk for exacerbations of COPD (ECOPD). The binding of IgG to its receptor, the Fc receptor for IgG (FcγR) on immune cells, has a critical role in determining antibody levels and function. In addition to our research demonstrating that IgG heavy chain gene (IGHG) variants are associated with ECOPD, single nucleotide variants (SNVs) in genes encoding FcγR (FCGR1-3, which encode receptor subtypes FcγRI, FcγRIIa/b/c, and FcγRIIIa/b) may also result in antibody deficiency and increased exacerbation risk. Due to technical challenges in accurately identifying SNVs in FCGR, this region has not been well-characterized. The limited data that exist are from people of European descent, and prior studies have not included African American participants. We therefore sought to investigate the hypothesis that distinct SNVs in genes encoding FcγR are associated with disease severity and history of exacerbations in African American people with COPD. Methods: We developed a novel pipeline to identify SNVs in the coding (CDS) regions of chromosome 1 using short-read whole genome sequence data. The pipeline was benchmarked using paired long-read samples from Genome in a Bottle. SNVs were called within CDS regions and analyzed in a meta-analysis of self-reported African American participants in SPIROMICS and COPDGene (n=3063). Genetic variants were tested for association with COPD severity (GOLD spirometry stage 1-2 vs 3-4) as well as COPD exacerbations, adjusting for age, sex and principal components controlling for population structure. Results: Eight SNVs were significantly associated with frequent ECOPD (≥2 in one year) in the meta-analysis of African American COPDGene and SPIROMICS participants (Table). Seven of these 8 SNVs were found in FCGR3; 4 in the activating FCGR3A subtype, and 3 in FCGR3B. Seven of 11 SNVs associated with COPD severity were in FCGR3 (4 in FCGR3A; 3 in FCGR3B). One SNV (rs371849) was associated with both frequent exacerbations (P=0.002) and COPD severity (P=0.044). Conclusions: We used a cutting-edge variant calling pipeline to identify multiple SNVs in FCGR, primarily involving FcγRIII receptor subtypes, associated with COPD severity and exacerbations in African American participants in SPIROMICS and COPDGene. FcγRIII variants are known to cause impaired antibody levels and function in people of European descent. The structural and functional importance of newly recognized variants in African American cohorts require further study, as they may represent immunogenetic risk factors for antibody deficiency and exacerbations.