Cause-Specific Excess Mortality in the US During the COVID-19 Pandemic (preprint)

The COVID-19 pandemic was a significant shock to United States mortality, and it is important to understand how the pandemic impacted other causes of death. We estimated monthly excess mortality in the US by cause of death, age, and sex, for official deaths at ages 15 and older. Data come from the CDC Wonder Multiple Cause of Death database. We used a compositionally robust Generalized Additive Model (GAM) to estimate expected mortality counts in March 2020-December 2022 for eight causes of death: accidents, cardiovascular diseases, cancer, diabetes, influenza and pneumonia, substance-related (drugs and alcohol), suicide, and residual (including COVID-19 related deaths). Analyses were stratified by sex and 15-year age groups from 15-29 to 75+. Excess mortality was calculated as observed deaths minus expected deaths. From March 2020 to December 2022, we estimated 1 298 763 total excess deaths (95% CI: 1 226 542 to 1 370 804). While there were fewer deaths than expected due to some causes like flu/pneumonia and suicide, the largest number of excess deaths, excluding COVID-19, were attributed to cardiovascular diseases (115 765 deaths, 95% CI:  98 697 to 133 783) and substance use (86 637 deaths, 95% CI: 79 273 to 93 690). Percent excess substance-related mortality was high across all ages, while percent excess from cardiovascular diseases was highest at midlife ages. Some of these excess cardiovascular deaths were likely due to undercounted COVID-19 deaths, but others may reflect indirect impacts of the pandemic on healthcare utilization or longer-term effects of COVID-19 infections.

Coding of Obesity-related Mortality Impacts Estimates of Obesity on U.S. Life Expectancy (preprint)

Background High levels of obesity remain an important population health problem in the U.S. and a possible contributor to stalling life expectancy. However, reliable estimates of the contribution of obesity to mortality in the U.S. are lacking, because of inconsistent coding of obesity-related causes of death. Methods We compare five International Classification of Diseases version 10 (ICD-10) coding schemes for obesity-related mortality used in the literature and examine how the magnitude of obesity-related mortality burdens varies across different schemes. We use U.S. multiple cause of death data and population estimates for the Black, white, and Latino population in the years 2010, 2015, and 2020. In sex- and race/ethnic-stratified analyses, we estimate the potential years of life expectancy gained if obesity-related mortality had not occurred as measured by each coding scheme. Results We estimate that obesity-related mortality contributes to up to 78 months (6.5 years) of lost U.S. life expectancy, though estimates range from as low as 0 months, with a median contribution across ICD-10 coding schemes of about 20 months (1.7 years). Despite substantial variation across coding schemes, obesity-related mortality consistently contributes more to life expectancy deficits for Black Americans compared to white and Latino Americans. Across all ICD-10 coding schemes, the age pattern of obesity follows a J-shaped curve, suggesting exponential increases in obesity-related mortality after age 25. Conclusions The estimation of the burden of obesity-related mortality on life expectancy in the United States varies widely depending on the causes of death used in analyses. This inconsistency may obscure our understanding of the contribution of obesity-related mortality to trends in life expectancy. We propose a standardization of the coding of obesity-related mortality for future studies and outline which causes should be included.

Significant impacts of the COVID-19 pandemic on race/ethnic differences in USA mortality (preprint)

The COVID-19 pandemic triggered declines in life expectancy at birth around the world. The United States of America (USA) was hit particularly hard among high income countries. Early data from the USA showed that these losses varied greatly by race/ethnicity in 2020, with Hispanic and Black Americans suffering much larger losses in life expectancy compared to white people. We add to this research by examining trends in lifespan inequality, average years of life lost, and the contribution of specific causes of death and ages to race/ethnic life expectancy disparities in the USA from 2010 to 2020. We find that life expectancy in 2020 fell more for Hispanic and Black males (4.5 years and 3.6 years, respectively) compared to white males (1.5 years). These drops nearly eliminated the previous life expectancy advantage for the Hispanic compared to white population, while dramatically increasing the already large gap in life expectancy between Black and white people. While the drops in life expectancy for the Hispanic population were largely attributable to official COVID-19 deaths, Black Americans additionally saw increases in cardiovascular disease and 'deaths of despair' over this period. In 2020, lifespan inequality increased slightly for Hispanic and white populations, but decreased for Black people, reflecting the younger age pattern of COVID-19 deaths for Hispanic people. Overall, the mortality burden of the COVID-19 pandemic hit race/ethnic minorities particularly hard in the USA, underscoring the importance of the social determinants of health during a public health crisis.

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.

Estimating the burden of COVID-19 on mortality, life expectancy and lifespan inequality in England and Wales: A population-level study (preprint)

ObjectiveTo determine the impact of the COVID-19 pandemic on mortality, life expectancy and lifespan inequality in the first half of 2020 (from week 1 to week 26 starting June 22) in England and Wales. DesignDemographic analysis of all-cause mortality from week 1 through week 26 of 2020 using publicly available death registration data from the Office for National Statistics. Setting and populationEngland and Wales population by age and sex in 2020. Main outcome measureAge and sex-specific excess mortality risk and deaths above a baseline adjusted for seasonality in the first half of 2020. We additionally provide estimates of life expectancy at birth and lifespan inequality defined as the standard deviation in age at death. ResultsWe estimate that there have been 53,937 (95% Prediction Interval: 53,092, 54,746) excess deaths in the first half of 2020, 54% of which occurred in men. Excess deaths increased sharply with age and men experienced elevated risks of death in all age groups. Life expectancy at birth dropped 1.7 and 1.9 years for females and males relative to the 2019 levels, respectively. Lifespan inequality also fell over the same period. ConclusionsQuantifying excess deaths and their impact on life expectancy at birth provides a more comprehensive picture of the full COVID-19 burden on mortality. Whether mortality will return to - or even fall below - the baseline level remains to be seen as the pandemic continues to unfold and diverse interventions are put in place. Summary boxesO_ST_ABSWhat is already known on this topicC_ST_ABSCOVID-19 related deaths may be misclassified as other causes of death thereby underestimating the full impact of the pandemic on mortality. Excess mortality, the difference between observed deaths and what would have been expected in the absence of the pandemic, is a useful metric to quantify the overall impact of the pandemic on mortality and population health. Life expectancy at birth and lifespan inequality assess the cumulative impact of the pandemic on population health. What this study addsWe examine death registration data from the Office for National Statistics from 2015 to week 26 (mid-year) in 2020 to quantify the impact of the COVID-19 pandemic on mortality in England and Wales thus far. We estimate excess mortality risk by age and sex, and quantify the impact of excess mortality risk on excess deaths, life expectancy and lifespan inequality. During weeks 10 through 26 of 2020, elevated mortality rates resulted in 53,937 additional deaths compared with baseline mortality. Life expectancy at birth for males and females in the first half of 2020 was 78 and 81.8 years, which represent a decline of 1.9 and 1.7 years of life lost relative to the year 2019. Lifespan inequality, a measure of the spread or variation in ages at death, declined due to the increase of mortality at older ages.

Social network-based distancing strategies to flatten the COVID 19 curve in a post-lockdown world (preprint)

Social distancing and isolation have been introduced widely to counter the COVID-19 pandemic. However, more moderate contact reduction policies become desirable owing to adverse social, psychological, and economic consequences of a complete or near-complete lockdown. Adopting a social network approach, we evaluate the effectiveness of three targeted distancing strategies designed to 'keep the curve flat' and aid compliance in a post-lockdown world. These are limiting interaction to a few repeated contacts, seeking similarity across contacts, and strengthening communities via triadic strategies. We simulate stochastic infection curves that incorporate core elements from infection models, ideal-type social network models, and statistical relational event models. We demonstrate that strategic reduction of contact can strongly increase the efficiency of social distancing measures, introducing the possibility of allowing some social contact while keeping risks low. This approach provides nuanced insights to policy makers for effective social distancing that can mitigate negative consequences of social isolation.

Demographic science aids in understanding the spread and fatality rates of COVID-19 (preprint)

Governments around the world must rapidly mobilize and make difficult policy decisions to mitigate the COVID-19 pandemic. Because deaths have been concentrated at older ages, we highlight the important role of demography, particularly how the age structure of a population may help explain differences in fatality rates across countries and how transmission unfolds. We examine the role of age structure in deaths thus far in Italy and South Korea and illustrate how the pandemic could unfold in populations with similar population sizes but different age structures, showing a dramatically higher burden of mortality in countries with older versus younger populations. This powerful interaction of demography and current age-specific mortality for COVID-19 suggests that social distancing and other policies to slow transmission should consider both the age composition of local and national contexts as well as the social connectedness of older and younger generations. We also call for countries to provide case and fatality data disaggregated by age and sex to improve real-time targeted nowcasting.