Contribution of the Elevated Thrombosis Risk of Males to the Excess Male Mortality Observed in COVID-19: An Observational Study

Abstract

Background: The mortality rate of COVID-19 is elevated in males compared to females.Objective: Determine the extent that the elevated thrombotic risk in males relative to females contributes to excess COVID-19 mortality in males.Design: Observational study.Setting: Data sourced from electronic medical records from over 200 US hospital systems.Participants: 60,877 patients hospitalized with COVID-19.Exposure: Exposure variable: biological sex; key variable of interest: thrombosis.Main outcome measures: Primary outcome was COVID-19 mortality. We measured: 1) mortality rate of males relative to females, 2) rate of thrombotic diagnoses occurring during hospitalization for COVID-19 in both sexes, and 3) mortality rate when evidence of thrombosis was present.Results: The COVID-19 mortality rate of males was 29.9% higher than that of females. Males had a 35.8% higher rate of receiving a thrombotic diagnosis compared to females. The mortality rate of all patients with a thrombotic diagnosis was 40.0%— over twice that of COVID-19 patients without a thrombotic diagnosis (adjusted OR 2.50 [2.37 to 2.64], p-value < .001). When defining thrombosis as either a documented thrombotic diagnosis or a D-dimer level ≥ 3.0 μg/mL, 16.4% of the excess mortality in male patients could be explained by increased thrombotic risk. Conclusions and Relevance: Our findings suggest the higher COVID-19 mortality rate in males may be significantly accounted for by the elevated risk for thrombosis among males. Understanding the mechanisms that underlie increased male thrombotic risk may allow for the advancement of effective anticoagulation strategies that reduce COVID-19 mortality in males.

Associations between SARS-CoV-2 infections and thrombotic complications necessitating surgical intervention: A systematic review

“…Several studies have attempted to quantify mortality related to thromboembolic events in COVID-19 patients. One study found that COVID-19 patients with a thromboembolic event had a 40% mortality rate, over twice that of COVID patients without a thrombotic event[ 44 ]. Another study, a meta-analysis of 8271 patients, found that patients with COVID-19 who had thromboembolic events had a pooled mortality rate of 23%, with thromboembolism significantly increasing the odds of mortality by as high as 74%[ 45 ].…”