Peripheral immune function and Alzheimer's disease: a living systematic review and critical appraisal.

BACKGROUND: A growing body of literature examines the relationship between peripheral immune function and Alzheimer's Disease (AD) in human populations. Our living systematic review summarizes the characteristics and findings of these studies, appraises their quality, and formulates recommendations for future research. METHODS: We searched the electronic databases PubMed, PsycINFO, and Web of Science, and reviewed references of previous reviews and meta-analyses to identify human studies examining the relationship between any peripheral immune biomarkers and AD up to September 7th, 2023. We examined patterns of reported statistical associations (positive, negative, and null) between each biomarker and AD across studies. Evidence for each biomarker was categorized into four groups based on the proportion of studies reporting different associations: corroborating a positive association with AD, a negative association, a null association, and presenting contradictory findings. A modified Newcastle-Ottawa scale (NOS) was employed to assess the quality of the included studies. FINDINGS: In total, 286 studies were included in this review. The majority were cross-sectional (n = 245, 85.7%) and hospital-based (n = 248, 86.7%), examining relationships between 187 different peripheral immune biomarkers and AD. Cytokines were the most frequently studied group of peripheral immune biomarkers. Evidence supported a positive association with AD for six biomarkers, including IL-6, IL-1ß, IFN-γ, ACT, IL-18, and IL-12, and a negative association for two biomarkers, including lymphocytes and IL-6R. Only a small proportion of included studies (n = 22, 7.7%) were deemed to be of high quality based on quality assessment. INTERPRETATION: Existing research on peripheral immune function and AD exhibits substantial methodological variations and limitations, with a notable lack of longitudinal, population-based studies investigating a broad range of biomarkers with prospective AD outcomes. The extent and manner in which peripheral immune function can contribute to AD pathophysiology remain open questions. Given the biomarkers that we identified to be associated with AD, we posit that targeting peripheral immune dysregulation may present a promising intervention point to reduce the burden of AD.

Exposure, Susceptibility, and Recovery: A Framework for Examining the Intersection of the Social and Physical Environments and Infectious Disease Risk.

Despite well-documented evidence that structurally disadvantaged populations are disproportionately affected by infectious diseases, our understanding of the pathways that connect structural disadvantage to the burden of infectious diseases is limited. We propose a conceptual framework to facilitate more rigorous examination and testing of hypothesized mechanisms through which social and environmental factors shape the burden of infectious diseases and lead to persistent inequities. Drawing upon the principles laid out by Link and Phelan in their landmark paper on social conditions (J Health Soc Behav. 1995;(spec no.):80-94), we offer an explication of potential pathways through which structural disadvantage (e.g., racism, sexism, and economic deprivation) operates to produce infectious disease inequities. Specifically, we describe how the social environment affects an individual's risk of infectious disease by 1) increasing exposure to infectious pathogens and 2) increasing susceptibility to infection. This framework will facilitate both the systematic examination of the ways in which structural disadvantage shapes the burden of infectious disease and the design of interventions that can disrupt these pathways.

Identifying patterns of reported findings on long-term cardiac complications of COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Prior reviews synthesized findings of studies on long-term cardiac complications of COVID-19. However, the reporting and methodological quality of these studies has not been systematically evaluated. Here, we conducted a systematic review and meta-analysis on long-term cardiac complications of COVID-19 and examined patterns of reported findings by study quality and characteristics. METHODS: We searched for studies examining long-term cardiac complications of COVID-19 that persisted for 4 weeks and over. A customized Newcastle-Ottawa scale (NOS) was used to evaluate the quality of included studies. Meta-analysis was performed to generate prevalence estimates of long-term cardiac complications across studies. Stratified analyses were further conducted to examine the prevalence of each complication by study quality and characteristics. The GRADE approach was used to determine the level of evidence for complications included in the meta-analysis. RESULTS: A total number of 150 studies describing 57 long-term cardiac complications were included in this review, and 137 studies reporting 17 complications were included in the meta-analysis. Only 25.3% (n = 38) of studies were of high quality based on the NOS quality assessment. Chest pain and arrhythmia were the most widely examined long-term complications. When disregarding study quality and characteristics, summary prevalence estimates for chest and arrhythmia were 9.79% (95% CI 7.24-13.11) and 8.22% (95% CI 6.46-10.40), respectively. However, stratified analyses showed that studies with low-quality scores, small sample sizes, unsystematic sampling methods, and cross-sectional design were more likely to report a higher prevalence of complications. For example, the prevalence of chest pain was 22.17% (95% CI 14.40-32.55), 11.08% (95% CI 8.65-14.09), and 3.89% (95% CI 2.49-6.03) in studies of low, medium, and high quality, respectively. Similar patterns were observed for arrhythmia and other less examined long-term cardiac complications. CONCLUSION: There is a wide spectrum of long-term cardiac complications of COVID-19. Reported findings from previous studies are strongly related to study quality, sample sizes, sampling methods, and designs, underscoring the need for high-quality epidemiologic studies to characterize these complications and understand their etiology.

Socioeconomic and race/ethnic differences in immunosenescence: Evidence from the Health and Retirement Study.

BACKGROUND: The COVID-19 pandemic has highlighted the urgent need to understand variation in immunosenescence at the population-level. Thus far, population patterns of immunosenescence have not well described. METHODS: We characterized measures of immunosenescence from the 2016 Venous Blood Study from the nationally representative U.S Health and Retirement Study (HRS) of individuals ages 50 years and older. RESULTS: Median values of the CD8+:CD4+, EMRA:Naïve CD4+ and EMRA:Naïve CD8+ ratios were higher among older participants and were lower in those with additional educational attainment. Generally, minoritized race and ethnic groups had immune markers suggestive of a more aged immune profile: Hispanics had a CD8+:CD4+ median value of 0.37 (95 % CI: 0.35, 0.39) compared to 0.30 in non-Hispanic Whites (95 % CI: 0.29, 0.31). Non-Hispanic Blacks had the highest median value of the EMRA:Naïve CD4+ ratio (0.08; 95 % CI: 0.07, 0.09) compared to non-Hispanic Whites (0.03; 95 % CI: 0.028, 0.033). In regression analyses, race/ethnicity and education were associated with large differences in the immune ratio measures after adjustment for age and sex. CONCLUSIONS: Lower educational attainment and minoritized racial ethnic status were associated with higher levels of immunosenescence. This population variation may have important implications for both risk of age-related disease and vulnerability to emerging pathogens (e.g., SARS-CoV-2).

The Association Between Cytomegalovirus and Disability by Race/Ethnicity and Sex: Results From the Health and Retirement Study.

Recent studies have documented a decline in the overall prevalence of disability in the United States; however, racial/ethnic and sex disparities continue to persist. Cytomegalovirus (CMV) infection, a socially patterned exposure, may be a key mechanism in understanding these previously documented disparities. Using data from a nationally representative study, the 2016 Health and Retirement Study, we employed Poisson log-binomial models to estimate the prevalence of disability in a comparison of CMV-seropositive and -seronegative adults and investigated effect modification by race/ethnicity and sex. Among the 9,029 participants (55% women; mean age = 67.4 years), 63% were CMV-seropositive and 15% were disabled. CMV seropositivity was highest among non-Hispanic Black (88%) and Hispanic (92%) adults as compared with non-Hispanic White adults (57%). We found evidence for effect modification in the association between CMV and disability by sex but not race/ethnicity. While the 95% confidence intervals in the fully adjusted models included the null value, in comparison with seronegative women, our results suggest a greater prevalence of disability among CMV-seropositive women (prevalence ratio = 1.16, 95% confidence interval: 0.97, 1.38) but not among men (prevalence ratio = 0.85, 95% confidence interval: 0.69, 1.06). Results provide initial support for the hypothesis that CMV may be an important determinant of sex disparities in disability.

A Geography of Risk: Structural Racism and Coronavirus Disease 2019 Mortality in the United States.

Coronavirus disease 2019 (COVID-19) is disproportionately burdening racial and ethnic minority groups in the United States. Higher risks of infection and mortality among racialized minorities are a consequence of structural racism, reflected in specific policies that date back centuries and persist today. Yet our surveillance activities do not reflect what we know about how racism structures risk. When measuring racial and ethnic disparities in deaths due to COVID-19, the Centers for Disease Control and Prevention statistically accounts for the geographic distribution of deaths throughout the United States to reflect the fact that deaths are concentrated in areas with different racial and ethnic distributions from those of the larger United States. In this commentary, we argue that such an approach misses an important driver of disparities in COVID-19 mortality, namely the historical forces that determine where individuals live, work, and play, and that consequently determine their risk of dying from COVID-19. We explain why controlling for geography downplays the disproportionate burden of COVID-19 on racialized minority groups in the United States. Finally, we offer recommendations for the analysis of surveillance data to estimate racial disparities, including shifting from distribution-based to risk-based measures, to help inform a more effective and equitable public health response to the pandemic.

Association Between Immune Response to Cytomegalovirus and Cognition in the Health and Retirement Study.

Chronic infections and the subsequent immune response have recently been shown to be risk factors for cognitive decline and Alzheimer disease and related dementias (ADRD). While some studies have shown an association between cytomegalovirus (CMV), a chronic and highly prevalent infection, and cognition and/or ADRD, these studies have been limited by nonrepresentative and small samples. Using 2016 data on 5,617 adults aged 65 years or more from the Health and Retirement Study, we investigated the cross-sectional associations of both CMV serostatus and immunoglobulin G (IgG) antibody response with cognitive function using linear regression models adjusting for age, sex, race/ethnicity, and educational attainment. We further investigated potential effect-measure modification by educational attainment. Overall, both CMV seropositivity and higher IgG antibody response were associated with lower cognitive function, though the relationship was not statistically significant in adjusted models. Among participants with less than a high school diploma, CMV seropositivity and being in the first tertile of IgG response, relative to seronegative persons, were associated with lower scores on the Telephone Interview for Cognitive Status (-0.56 points (95% confidence interval: -1.63, 0.52) and -0.89 points (95% confidence interval: -2.07, 0.29), respectively), and the relationship was attenuated among those with higher education. Our results suggest that CMV may be a risk factor for cognitive impairment, particularly among persons with fewer educational resources.

Pathogen burden and leukocyte telomere length in the United States.

BACKGROUND: Prior studies in humans have suggested that telomere shortening may be accelerated by infection, but research on multiple pathogens and use of large population-based study samples has been limited. We estimated cross-sectional associations between seropositivity to five persistent pathogens (Herpes Simplex Virus Type-1 (HSV-1), Herpes Simplex Virus Type-2 (HSV-2), cytomegalovirus (CMV), Helicobacter pylori (H.pylori), and Hepatitis B) as well as total pathogen burden and leukocyte telomere length. Data were derived from the National Health and Nutrition Examination Survey (1999-2000) for individuals 20-49 years of age, N = 1708. We analyzed the influence of each pathogen separately, a pathogen count score and a latent class model of pathogen burden on log telomere length using linear regression models, adjusted for covariates. RESULTS: Individuals in a latent pathogen burden class characterized by high probabilities of infection with HSV-1, CMV, and H. pylori, had significantly decreased log telomere length (- 0.30 [95% CI: - 0.36, - 0.24]) compared to those in a latent class characterized by low probabilities of all five infections. There were limited significant associations using other pathogen measures. CONCLUSIONS: These results suggest that infection with specific combinations of pathogens may be one mechanism contributing to accelerated cellular senescence with possible origins early in the life course.

Social patterning of acute respiratory illnesses in the Household Influenza Vaccine Evaluation (HIVE) Study 2014-2015.

Social patterning of infectious diseases is increasingly recognised. Previous studies of social determinants of acute respiratory illness (ARI) have found that highly educated and lower income families experience more illnesses. Subjective social status (SSS) has also been linked to symptomatic ARI, but the association may be confounded by household composition. We examined SSS and ARI in the Household Influenza Vaccine Evaluation (HIVE) Study in 2014-2015. We used SSS as a marker of social disadvantage and created a workplace disadvantage score for working adults. We examined the association between these measures and ARI incidence using mixed-effects Poisson regression models with random intercepts to account for household clustering. In univariate analyses, mean ARI was higher among children <5 years old (P < 0.001), and females (P = 0.004) at the individual level. At the household level, mean ARI was higher for households with at least one child <5 years than for those without (P = 0.002). In adjusted models, individuals in the lowest tertile of SSS had borderline significantly higher rates of ARI than those in the highest tertile (incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 0.98-1.92). Households in the lowest tertile of SSS had significantly higher ARI incidence in household-level models (IRR 1.46, 95% CI 1.05-2.03). We observed no association between workplace disadvantage and ARI. We detected an increase in the incidence of ARI for households with low SSS compared with those with high SSS, suggesting that socio-economic position has a meaningful impact on ARI incidence.

Understanding the intersection of race and place: the case of tuberculosis in Michigan.

BACKGROUND: Race and place intersect to produce location-based variation in disease distributions. We analyzed the geographic distribution of tuberculosis (TB) incidence in Michigan, USA to better understand the complex interplay between race and place, comparing patterns in Detroit, Wayne County and the state of Michigan as a whole. METHODS: Using cross-sectional TB surveillance data from the Michigan Department of Health and Human Services, multivariable statistical models were developed to analyze the residence patterns of TB incidence from 2007 through 2012. Two-way interactions among the residence location and race of cases were assessed. RESULTS: Overall, Detroit residents experienced 58% greater TB incidence than residents of Wayne County or the state of Michigan. Racial inequalities were less pronounced in Detroit compared to both Wayne County and the state of Michigan. Blacks in Detroit had 2.01 times greater TB incidence than Whites, while this inequality was 3.62 times more in Wayne County and 8.72 greater in the state of Michigan. CONCLUSION: Our results highlight how race and place interact to influence patterns of TB disease, and the ways in which this interaction is context dependent. TB elimination in the U.S. will require strategies that address the local social environment, as much as the physical environment.

The Modern Profile of Tuberculosis: Developing the TB Social Survey to understand contemporary social patterns in tuberculosis.

Social disparities in tuberculosis have been documented for decades, yet to date there has not been a comprehensive study to examine the contemporary causes of these disparities. Local public health departments, and particularly public health nursing staff are charged with delivering directly observed therapy to individuals with tuberculosis disease. As a result of the frequency and duration of treatment, practitioners delivering therapy are often well-acquainted with the lives and challenges of their constituents. Thus, through these practitioners there exists a deep repository of knowledge on the drivers of social disparities in tuberculosis disease. Partnering with local public health departments, we developed a survey instrument aimed at understanding the social profile of individuals with tuberculosis disease in metropolitan Detroit, Michigan. We discuss the development and implementation of the survey instrument as well as challenges in developing partnerships between academic researchers and local public health practitioners. This study can serve as a framework for both academic researchers and public health practitioners interested in addressing social disparities in infectious disease.

Race and nativity are major determinants of tuberculosis in the U.S.: evidence of health disparities in tuberculosis incidence in Michigan, 2004-2012.

BACKGROUND: The incidence of TB in Michigan was 1.5 per 100,000 people in 2012, roughly half the U.S. incidence. Despite successes in TB control, disparities in TB still exist in Michigan, particularly by race, age, and nativity. A major challenge in understanding disparities in TB burden is distinguishing between TB cases resulting from recent transmission and those resulting from reactivation of latent TB infection, information critical to tailoring control strategies. We examined nine-year trends in tuberculosis (TB) incidence patterns for the entire population of Michigan, and within demographic subgroups. METHODS: Using a cross-sectional study of TB surveillance data, we analyzed 1254 TB cases reported in Michigan during 2004-2012. Cases included were those for whom both spoligotyping and 12-locus-MIRU-VNTR results were available. Using a combination of the genotyping information and time of diagnosis, we then classified cases as resulting from either recent transmission or reactivation of latent TB infection. We used multivariable negative binomial regression models to study trends in the TB incidence rate for the entire population and by race, nativity, gender, and age. RESULTS: Overall, the incidence rate of TB declined by an average of 8% per year-11% among recently transmitted cases, and 9% among reactivation cases. For recently transmitted disease, Blacks had an average incidence rate 25 times greater than Whites, after controlling for nativity, gender, and age. For disease resulting from latent TB infection Asians had an average incidence rate 24 times greater than Whites, after controlling for nativity, gender, and age. CONCLUSIONS: Disparities in incidence persist despite ongoing TB control efforts. Greater disparities were observed by race and nativity demonstrating some of the ways that TB incidence is socially patterned. Reducing these disparities will require a multi-faceted approach encompassing the social and environmental contexts of high-risk populations.

State variation in neighborhood COVID-19 burden across the United States.

BACKGROUND: A lack of fine, spatially-resolute case data for the U.S. has prevented the examination of how COVID-19 infection burden has been distributed across neighborhoods, a key determinant of both risk and resilience. Without more spatially resolute data, efforts to identify and mitigate the long-term fallout from COVID-19 in vulnerable communities will remain difficult to quantify and intervene on. METHODS: We leveraged spatially-referenced data from 21 states collated through the COVID Neighborhood Project to examine the distribution of COVID-19 cases across neighborhoods and states in the U.S. We also linked the COVID-19 case data with data on the neighborhood social environment from the National Neighborhood Data Archive. We then estimated correlations between neighborhood COVID-19 burden and features of the neighborhood social environment. RESULTS: We find that the distribution of COVID-19 at the neighborhood-level varies within and between states. The median case count per neighborhood (coefficient of variation (CV)) in Wisconsin is 3078.52 (0.17) per 10,000 population, indicating a more homogenous distribution of COVID-19 burden, whereas in Vermont the median case count per neighborhood (CV) is 810.98 (0.84) per 10,000 population. We also find that correlations between features of the neighborhood social environment and burden vary in magnitude and direction by state. CONCLUSIONS: Our findings underscore the importance that local contexts may play when addressing the long-term social and economic fallout communities will face from COVID-19.

A lack of data on the geographic location of COVID-19 cases in the U.S has limited our ability to examine how COVID-19 burden has been distributed across neighborhoods within U.S. states. It may be that certain neighborhoods have borne a disproportionate burden of COVID-19 and are more likely to experience greater long-term social and economic consequences from the pandemic. We used data from 21 states to examine the distribution of COVID-19 cases across neighborhoods and states in the U.S. We find that the distribution of COVID-19 varies widely both within neighborhoods in a state, and between states. We also find that the features of the neighborhood social environment that are correlated with neighborhood COVID-19 burden vary by state. Our findings show that the local neighborhood may play an important role in addressing long-term social and economic consequences from COVID-19.

The association between incarceration and housing insecurity and advanced immune age during late life.

Emerging evidence suggests that psychosocial stress ages the immune system. Accordingly, immune aging may be an important potential mechanism linking psychosocial stress to aging-related decline and disease. Incarceration and housing insecurity represent severe and complex experiences of a multitude of psychosocial stressors, including discrimination, violence, and poverty. In this study, we investigated the association between incarceration and/or housing insecurity and advanced immune age in adults aged 55 and older. Our sample was derived from the Health and Retirement Survey (HRS), with n = 7003 individuals with valid housing insecurity data and n = 7523 with valid incarceration data. From 2016 Venous Blood Study data, we assessed immune aging using a comprehensive set of immune markers including inflammatory markers (IL-6, CRP, s-TNFR1), markers of viral control (CMV IgG antibodies), and ratios of T cell phenotypes (CD8+:CD4+, CD+ Memory: Naïve, CD4+ Memory: Naïve, CD8+ Memory: Naïve ratios). We found that both incarceration and housing insecurity were strongly associated with more advanced immune aging as indicated by increased inflammation, reduced viral control, and reduction in naïve T cells relative to memory T cells. Given that those who experienced incarceration, housing insecurity, and/or are racialized minorities were less likely to be included in this study, our results likely underestimated these associations. Despite these limitations, our study provided strong evidence that experiencing incarceration and/or housing insecurity may accelerate the aging of the immune system.

The embodiment of the neighborhood socioeconomic environment in the architecture of the immune system.

There is growing recognition of the importance of immune health for understanding the origins of ageing-related disease and decline. Numerous studies have demonstrated consistent associations between the social determinants of health and immunosenescence (i.e. ageing of the immune system). Yet few studies have interrogated the relationship between neighborhood socioeconomic status (nSES) and biologically specific measures of immunosenescence. We used data from the US Health and Retirement Study to measure immunosenescence linked with neighborhood socioeconomic data from the National Neighborhood Data Archive to examine associations between indicators of nSES and immunosenescence. We found associations between both the ratio of terminally differentiated effector memory to naïve (EMRA:Naïve) CD4+ T cells and cytomegalovirus (CMV) immunoglobulin G (IgG) levels and nSES. For the CD4+ EMRA:Naïve ratio, each 1% increase in the neighborhood disadvantage index was associated with a 0.005 standard deviation higher value of the EMRA:Naïve ratio (95% CI: 0.0003, 0.01) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.05 higher standardized value of the CD4+ EMRA:Naïve ratio. The results were fully attenuated when adjusting for both individual-level SES and race/ethnicity. For CMV IgG antibodies, a 1% increase in neighborhood disadvantage was associated a 0.03 standard deviation higher value of CMV IgG antibodies (ß = 0.03; 95% CI: 0.002, 0.03) indicating that living in a neighborhood that is 10% higher in disadvantage is associated with a 0.3 higher standardized value of CMV. This association was attenuated though still statistically significant when controlling for individual-level SES and race/ethnicity. The findings from this study provide compelling initial evidence that large, nonspecific social exposures, such as neighborhood socioeconomic conditions, can become embodied in cellular processes of immune ageing.

Comparison of two area-level socioeconomic deprivation indices: Implications for public health research, practice, and policy.

OBJECTIVES: To compare 2 frequently used area-level socioeconomic deprivation indices: the Area Deprivation Index (ADI) and the Social Vulnerability Index (SVI). METHODS: Index agreement was assessed via pairwise correlations, decile score distribution and mean comparisons, and mapping. The 2019 ADI and 2018 SVI indices at the U.S. census tract-level were analyzed. RESULTS: Index correlation was modest (R = 0.51). Less than half (44.4%) of all tracts had good index agreement (0-1 decile difference). Among the 6.3% of tracts with poor index agreement (≥6 decile difference), nearly 1 in 5 were classified by high SVI and low ADI scores. Index items driving poor agreement, such as high rents, mortgages, and home values in urban areas with characteristics indicative of socioeconomic deprivation, were also identified. CONCLUSIONS: Differences in index dimensions and agreement indicated that ADI and SVI are not interchangeable measures of socioeconomic deprivation at the tract level. Careful consideration is necessary when selecting an area-level socioeconomic deprivation measure that appropriately defines deprivation relative to the context in which it will be used. How deprivation is operationalized affects interpretation by researchers as well as public health practitioners and policymakers making decisions about resource allocation and working to address health equity.

State Variation in Neighborhood COVID-19 Burden: Findings from the COVID Neighborhood Project.

A lack of fine, spatially-resolute case data for the U.S. has prevented the examination of how COVID-19 burden has been distributed across neighborhoods, a known geographic unit of both risk and resilience, and is hampering efforts to identify and mitigate the long-term fallout from COVID-19 in vulnerable communities. Using spatially-referenced data from 21 states at the ZIP code or census tract level, we documented how the distribution of COVID-19 at the neighborhood-level varies significantly within and between states. The median case count per neighborhood (IQR) in Oregon was 3,608 (2,487) per 100,000 population, indicating a more homogenous distribution of COVID-19 burden, whereas in Vermont the median case count per neighborhood (IQR) was 8,142 (11,031) per 100,000. We also found that the association between features of the neighborhood social environment and burden varied in magnitude and direction by state. Our findings underscore the importance of local contexts when addressing the long-term social and economic fallout communities will face from COVID-19.

Biological expressions of early life trauma in the immune system of older adults.

BACKGROUND: Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. METHODS: Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. FINDINGS: Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (ß = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (ß = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. INTERPRETATION: Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.