Law, policy, biology, and sex: Critical issues for researchers.

Researchers should be aware of how sex-difference science is (mis)applied in legal and policy contexts.

Sex disparities in COVID-19 outcomes in the United States: Quantifying and contextualizing variation.

This paper presents the first longitudinal study of sex disparities in COVID-19 cases and mortalities across U.S. states, derived from the unique 13-month dataset of the U.S. Gender/Sex COVID-19 Data Tracker. To analyze sex disparities, weekly case and mortality rates by sex and mortality rate ratios were computed for each U.S. state, and a multilevel crossed-effects conditional logistic binomial regression model was fitted to estimate the variation of the sex disparity in mortality over time and across states. Results demonstrate considerable variation in the sex disparity in COVID-19 cases and mortalities over time and between states. These data suggest that the sex disparity, when present, is modest, and likely varies in relation to context-sensitive variables, which may include health behaviors, preexisting health status, occupation, race/ethnicity, and other markers of social experience.

Challenging the binary: Gender/sex and the bio-logics of normalcy.

BACKGROUND: We are witnessing renewed debates regarding definitions and boundaries of human gender/sex, where lines of genetics, gonadal hormones, and secondary sex characteristics are drawn to defend strict binary categorizations, with attendant implications for the acceptability and limits of gender identity and diversity. AIMS: Many argue for the need to recognize the entanglement of gender/sex in humans and the myriad ways that gender experience becomes biology; translating this theory into practice in human biology research is essential. Biological anthropology is well poised to contribute to these societal conversations and debates. To do this effectively, a reconsideration of our own conceptions of gender/sex, gender identity, and sexuality is necessary. METHODS: In this article, we discuss biological variation associated with gender/sex and propose ways forward to ensure we are engaging with gender/sex diversity. We base our analysis in the concept of "biological normalcy," which allows consideration of the relationships between statistical distributions and normative views. We address the problematic reliance on binary categories, the utilization of group means to represent typical biologies, and document ways in which binary norms reinforce stigma and inequality regarding gender/sex, gender identity, and sexuality. DISCUSSION AND CONCLUSIONS: We conclude with guidelines and methodological suggestions for how to engage gender/sex and gender identity in research. Our goal is to contribute a framework that all human biologists can use, not just those who work with gender or sexually diverse populations. We hope that in bringing this perspective to bear in human biology, that novel ideas and applications will emerge from within our own discipline.

Sex Disparities in COVID-19 Mortality Vary Across US Racial Groups.

BACKGROUND: Inequities in COVID-19 outcomes in the USA have been clearly documented for sex and race: men are dying at higher rates than women, and Black individuals are dying at higher rates than white individuals. Unexplored, however, is how sex and race interact in COVID-19 outcomes. OBJECTIVE: Use available data to characterize COVID-19 mortality rates within and between race and sex strata in two US states, with the aim of understanding how apparent sex disparities in COVID-19 deaths vary across race. DESIGN AND PARTICIPANTS: This observational study uses COVID-19 mortality data through September 21, 2020, from Georgia (GA) and Michigan (MI). MAIN MEASURES: We calculate age-specific rates for each sex-race-age stratum, and age-standardized rates for each race-sex stratum. We investigate the sex disparity within race groups and the race disparity within sex groups using age-standardized rate ratios, and rate differences. KEY RESULTS: Within race groups, men have a higher COVID-19 mortality rate than women. Black men have the highest rate of all race-sex groups (in MI: 254.6, deaths per 100,000, 95% CI: 241.1-268.2, in GA:128.5, 95% CI: 121.0-135.9). In MI, the COVID-19 mortality rate for Black women (147.1, 95% CI: 138.7-155.4) is higher than the rate for white men (39.1, 95% CI: 37.3-40.9), white women (29.7, 95% CI: 28.3-31.0), and Asian/Pacific Islander men and women. COVID-19 mortality rates in GA followed the same pattern. In MI, the male:female mortality rate ratio among Black individuals is 1.7 (1.5-2.0) while the rate ratio among White individuals is only 1.3 (1.2-1.5). CONCLUSION: While overall, men have higher COVID-19 mortality rates than women, our findings show that this sex disparity does not hold across racial groups. This demonstrates the limitations of unidimensional reporting and analyses and highlights the ways that race and gender intersect to shape COVID-19 outcomes.

Variability of C-reactive protein in first-generation Ecuadorian immigrants living in the United States.

OBJECTIVES: Establish the variability of C-reactive protein (CRP) within a population of first-generation immigrants living in the United States. Prior work has theorized that individuals with high levels of childhood pathogen exposure may have lower CRP levels in adulthood, and therefore that for these individuals, CRP may not be as accurate an index of chronic disease risk related to low-level inflammation as is presumed based on data from wealthy populations. This potentially has major implications for the interpretation of CRP as a biomarker of chronic inflammation. METHODS: This longitudinal study collected a total of 125 dried blood spot (DBS) samples from 31 participants (median 4 samples each) and CRP levels in these DBS were assayed by enzyme-linked immunosorbant assay. Surveys were administered to characterize childhood pathogen exposure, and current illness. Variance was estimated using mixed effects regression models. RESULTS: On average, participants were adults (mean = 41.9 years old) who had immigrated to the United States nearly 20 years prior to the study and had nearly universally experienced childhood helminth infection and other major pathogen exposures. Median serum-equivalent CRP was 0.77 mg/L. Individuals reliably differed in subacute CRP levels, and, depending on whether untransformed or log-transformed CRP was the outcome variable, 45% or 62% of variance in CRP was attributable to between-individual differences. CONCLUSIONS: The variability of CRP levels in individuals with relatively high childhood pathogen exposure is comparable to previously reported studies in North America and Europe. However, CRP values are relatively low. CRP is an appropriate measure of subacute inflammation in this sample.

Energetics and the immune system: Trade-offs associated with non-acute levels of CRP in adolescent Gambian girls.

BACKGROUND AND OBJECTIVES: The human immune system is an ever-changing composition of innumerable cells and proteins, continually ready to respond to pathogens or insults. The cost of maintaining this state of immunological readiness is rarely considered. In this paper we aim to discern a cost to non-acute immune function by investigating how low levels of C-reactive protein (CRP) relate to other energetic demands and resources in adolescent Gambian girls. METHODOLOGY: Data from a longitudinal study of 66 adolescent girls was used to test hypotheses around investment in immune function. Non-acute (under 2 mg/L) CRP was used as an index of immune function. Predictor variables include linear height velocity, adiposity, leptin, and measures of energy balance. RESULTS: Non-acute log CRP was positively associated with adiposity (ß = 0.16, p < 0.001, R2 = 0.17) and levels of the adipokine leptin (ß = 1.17, p = 0.006, R2 = 0.09). CRP was also negatively associated with increased investment in growth, as measured by height velocity (ß = -0.58, p < 0.001, R2 = 0.13) and lean mass deposition ß = -0.42, p = 0.005, R2 = 0.08). Relationships between adiposity and growth explained some, but not all, of this association. We do not find that CRP was related to energy balance. CONCLUSIONS AND IMPLICATIONS: These data support a hypothesis that investment in non-acute immune function is facultative, and sensitive to energetic resources and demands. We also find support for an adaptive association between the immune system and adipose tissue.