Mediation of the sex disparity in COVID-19 mortality by arterial and venous thromboembolism: a multicenter cohort study the Dutch COVID & Thrombosis Coalition.

Authors

Daniek A M Meijs, Chantal Visser, Mark J R Smeets, Eva K Kempers, Lloyd Brandts, Bernard J van Varik, Chahinda Ghossein-Doha, Iwan C C van der Horst, Marieke J H A Kruip, Hugo Ten Cate, Suzanne C Cannegieter, Bas C T van Bussel, Dutch COVID & Thrombosis Coalition

Published in

Journal of thrombosis and haemostasis : JTH. Sep 21, 2026. Epub Sep 21, 2026.

Abstract

Previous studies have demonstrated a notable sex difference in Coronavirus Disease 2019 (COVID-19) mortality without a clear explanation. Concurrent thrombosis could underlie this sex disparity.
To investigate whether differentially occurring venous and arterial thromboembolic events (VTE and ATE, respectively) explain the association between sex and mortality in COVID-19 patients.
A multicenter cohort study in the Netherlands was conducted between February 2020 and May 2022. Suspected or confirmed COVID-19 patients admitted to the ward or Intensive Care Unit (ICU) were included. All-cause mortality, VTE, and ATE were the primary outcomes. Counterfactual mediation analyses with a random intercept for center were performed to decompose the total effect of sex on mortality into the natural direct effect (NDE; i.e. the effect of sex on mortality not operating through VTE/ATE) and natural indirect effect (NIE; i.e. the effect of sex on mortality mediated by VTE/ATE), and to estimate the proportion mediated (PM; fraction of the total effect explained by VTE/ATE) through VTE and ATE.
3255 COVID-19 patients were included. Females showed lower cumulative incidences of mortality (15 vs. 22%), VTE (10 vs. 16%), and ATE (1.4 vs. 3%) than males. Females demonstrated lower OR for mortality (OR 0.59 (95%CI 0.49-0.72)), VTE (OR 0.57 (95%CI 0.46-0.72)) and ATE (OR 0.64 (95%CI 0.39-1.03)) than males. Counterfactual mediation analyses showed that the proportions mediated were 7.95% (95%CI 3.01-17.63%) for VTE and 3.28% (95%CI 0.42-8.68%) for ATE, respectively.
The lower incidence of VTE and ATE in females explains the sex difference in mortality in hospitalized COVID-19 patients, only to a minor extent. Further investigation is warranted to unravel sex-related factors in COVID-19.

PMID:
42767509
Bibliographic data and abstract were imported from PubMed on 22 Sep 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.