Sociodemographic Differences in Population-Level Immunosenescence in Older Age (preprint)

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 are not well described. Methods We characterized measures of immunosenescence from newly released venous blood data from the nationally representative U.S Health and Retirement Study (HRS) of individuals ages 56 years and older. Findings 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 Whites (95% CI: 0.29, 0.31). Blacks had the highest median value of the EMRA:Naïve CD4+ ratio (0.08; 95% CI: 0.07, 0.09) compared to 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. For example, each additional level of education was associated with roughly an additional decade of immunological age, and the racial/ethnic differences were associated with two to four decades of additional immunological age. Interpretation Our study provides novel insights into population variation in immunosenescence. This has implications for both risk of age-related disease and vulnerability to novel pathogens (e.g., SARS-CoV-2). Funding This study was partially funded by the U.S. National Institutes of Health, National Institute on Aging R00AG062749. AEA and GAN acknowledge support from the National Institutes of Health, National Institute on Aging R01AG075719. JBD acknowledges support from the Leverhulme Trust (Centre Grant) and the European Research Council grant ERC-2021-CoG-101002587 Research in context Evidence before this study Alterations in immunity with chronological aging have been consistently demonstrated across human populations. Some of the hallmark changes in adaptive immunity associated with aging, termed immunosenescence, include a decrease in naïve T-cells, an increase in terminal effector memory cells, and an inverted CD8:CD4 T cell ratio. Several studies have shown that social and psychosocial exposures can alter aspects of immunity and lead to increased susceptibility to infectious diseases. Add value of this study While chronological age is known to impact immunosenescence, there are no studies examining whether social and demographic factors independently impact immunosenescence. This is important because immunosenescence has been associated with greater susceptibility to disease and lower immune response to vaccination. Identifying social and demographic variability in immunosenescence could help inform risk and surveillance efforts for preventing disease in older age. To our knowledge, we present one of the first large-scale population-based investigations of the social and demographic patterns of immunosenescence among individuals ages 50 and older living in the US. We found differences in the measures of immunosenescence by age, sex, race/ethnicity, and education, though the magnitude of these differences varied across immune measures and sociodemographic subgroup. Those occupying more disadvantaged societal positions (i.e., minoritized race and ethnic groups and individuals with lower educational attainment) experience greater levels of immunosenescence compared to those in less disadvantaged positions. Of note, the magnitude of effect of sociodemographic factors was larger than chronological age for many of the associations. Implications for practice or policy and future research The COVID-19 pandemic has highlighted the need to better understand variation in adaptive and innate immunity at the population-level. While chronological age has traditionally been thought of as the primary driver of immunological aging, the magnitude of differences we observed by sociodemographic factors suggests an important role for the social environment in the aging human immune system.

A Global Study of COVID-19 Vaccination Intentions: The Role of Personal Experiences and Risk Perceptions (preprint)

Background: The COVID-19 pandemic presents an opportunity to assess the impact of personal experiences on vaccine decision-making. The aim of this study was to examine the associations between experiences with COVID-19 and intention to vaccinate against COVID-19. Methods We administered 28 repeated cross-sectional, online surveys between June 2020 and June 2021 in the US and Asia. The main exposures were three types of experiences: COVID-19 diagnosis, knowing a friend/family member with COVID-19, and exposures to media containing COVID-19 patients. A series of logistic regression models estimated the association between each experience and acceptance of a hypothetical COVID-19 vaccine. We also explored perceived susceptibility as a potential mediator. Results Intent to vaccinate was lowest in the US and Taiwan, and highest in India, Indonesia, and China. Personal diagnosis with COVID-19 had the greatest impact on intentions to vaccinate across country sites compared to those who experienced a friend or family member diagnosed with COVID-19 or exposures to personal stories reported through media. In India participants that reported a personal diagnosis with COVID-19 had 12.95 times the odds (95% CI: 4.89, 34.28) of accepting a COVID-19 vaccine compared to those with no diagnosis. Higher risk perceptions were associated with higher intention to vaccinate against COVID-19. Conclusions Proximity and seriousness of experiences are influential factors for intention to vaccinate against COVID-19. This study highlights the numerous ways in which pandemic experiences may influence intention to vaccinate against COVID-19 across geographies and cultures, where the course of the pandemic differed.

Inequality in acute respiratory infection outcomes in the United States: A review of the literature and its implications for public health policy and practice (preprint)

Seasonal and pandemic respiratory viruses such as influenza and the novel coronavirus (SARS-COV-2) currently sweeping the globe have often been described as ‘equal opportunity infectors’, implying little socioeconomic disparity in susceptibility. However, early data from the COVID-19 pandemic has underscored that the burden of respiratory viruses actually reflect and magnify existing socioeconomic inequalities. We review the literature on socioeconomic and racial disparities in acute respiratory infection (ARI), as well as ARI-associated hospitalization and mortality. Our goal is to identify key principles of the relationship between socioeconomic inequality and ARI outcomes, as well as highlighting poorly understood areas that need to be addressed by research and policy in the wake of the COVID-19 pandemic. We find that there has been descriptive work in this area, but that there is a distinct lack of cohesive methodology in the literature exploring social determinants and ARI. We propose the fundamental cause theory is a useful framework for guiding future research of disparities in ARI and for the design of interventions to alleviate these disparities.