Abstract
BACKGROUND: Men have consistently experienced higher COVID-19 mortality than women across most countries and time periods, prompting widespread investigation into potential biological causes. Early research focused on sex-related genetic, hormonal, and immunological mechanisms to explain these disparities. MAIN BODY: This narrative review traces the evolution of scientific explanations for women/men mortality differences in COVID-19, from early biological hypotheses to more nuanced gendered and intersectional models. While some studies suggest sex-linked genetic variants, chromosomal mechanisms, or hormone-regulated expression of viral entry receptors might partially explain men's higher mortality, the overall evidence remains inconsistent and inconclusive. Increasingly, attention has shifted to social and structural factors, including occupational exposure, pre-existing health conditions, healthcare access, and behaviors, that can differently shape vulnerability to COVID-19 in women and men. Data disaggregated by gender and race further revealed significant heterogeneity in outcomes, underscoring the influence of intersecting axes of inequality. International comparisons suggested that gender inequality at the societal level was associated with wider women/men COVID-19 mortality gaps. Analyses that overlook the interaction between sex- and gender-related factors and their intersection with racial disparities and socioeconomic status risk obscuring the underlying drivers of COVID-19 disparities. CONCLUSION: Sex-related biological factors may have influenced COVID-19 outcomes, but they do not adequately account for the observed differences in mortality between women and men. Approaching the study of health inequities through a gendered, intersectional framework is essential for accurately identifying and addressing underlying risk factors, and for better understanding how sex- and gender-related factors may interact, not only in COVID-19, but across a broad range of health conditions.