Sex differences in D-dimer and critical illness in patients with COVID-19: A systematic review and meta-analysis

BACKGROUND: Observed sex differences in COVID-19 outcomes suggest that men are more likely to experience critical illness and mortality. Thrombosis is common in severe COVID-19, and D-dimer is a significant marker for COVID-19 severity and mortality. It is unclear whether D-dimer levels differ between men and women, and the effect of D-dimer levels on disease outcomes remains under investigation. OBJECTIVES: We aimed to evaluate the sex difference in the D-dimer level among hospitalized patients with COVID-19 and the effect of sex and D-dimer level on disease outcomes. METHODS: We meta-analyzed articles reporting D-dimer levels in men and women hospitalized for COVID-19, until October 2021, using random effects. Primary outcomes were mortality, critical illness, and thrombotic complications. RESULTS: In total, 11,682 patients from 10 studies were analyzed (N = 5606 men (55.7%), N = 5176 women (44.3%)). Men had significantly higher odds of experiencing mortality (odds ratios (OR) = 1.41, 95% CI: [1.25, 1.59], P ≤ .001, I(2) = 0%) and critical illness (OR = 1.76, 95% CI: [1.43, 2.18], P ≤ .001, I(2) = 61%). The mean D-dimer level was not significantly different between men and women (MD = 0.08, 95% CI: [−0.23, 0.40], P = .61, I(2) = 52%). In the subgroup analysis, men had significantly higher odds of experiencing critical illness compared with women in both the “higher” (P = .006) and “lower” (P = .001) D-dimer subgroups. CONCLUSION: Men have significantly increased odds of experiencing poor COVID-19 outcomes compared with women. No sex difference was found in the D-dimer level between men and women with COVID-19. The diversity in D-dimer reporting impacts data interpretation and requires further attention.