Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry

Art Schuermans; Andreas Verstraete; Vilma Lammi; Tomoko Nakanishi; Maddalena Ardissino; Jef Van den Eynde; Benjamin B. Sun; Marios K. Georgakis; Beatriz Guillén‐Guío; Louise V. Wain; Christopher Edward Brightling; PHOSP-COVID Collaborative Group; Johan Van Weyenbergh; Adam J. Lewandowski; Betty Raman; Hugo Zeberg; Hanna Maria Ollila; Stephen Burgess; Pradeep Natarajan; Michael C. Honigberg; Kathleen Freson; Thomas Vanassche; Peter B. Verhamme

doi:10.1038/s44161-025-00749-4

Genetic & Genomic MedicineNature Cardiovascular ResearchDec 16, 2025

Peer-reviewed journal article

Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry

Art Schuermans iD, Andreas Verstraete iD, Vilma Lammi iD, Tomoko Nakanishi iD, Maddalena Ardissino iD, Jef Van den Eynde iD, Benjamin B. Sun iD, Marios K. Georgakis iD, Beatriz Guillén‐Guío iD, Louise V. Wain iD, Christopher Edward Brightling iD, PHOSP-COVID Collaborative Group, Johan Van Weyenbergh iD, Adam J. Lewandowski iD, Betty Raman iD, Hugo Zeberg iD, Hanna Maria Ollila iD, Stephen Burgess iD, Pradeep Natarajan iD, Michael C. Honigberg iD, Kathleen Freson iD, Thomas Vanassche iD, Peter B. Verhamme iD

Abstract

SARS-CoV-2 infection can result in long COVID, characterized by post-acute symptoms from multiple organs. Current hypotheses on mechanisms underlying long COVID include persistent inflammation and thromboembolism; however, compelling evidence from humans is limited and causal associations remain unclear. Here, we tested the association of thromboembolism-related genetic variants with long COVID in the Long COVID Host Genetics Initiative (ncases=3,018; ncontrols=994,582). Primary analyses revealed that each unit increase in the log-odds of genetically predicted venous thromboembolism risk was associated with 1.21-fold odds of long COVID (95%CI: 1.08-1.35; P=1.2x10-3). This association was independent of acute COVID-19 severity, robust across genetic instruments and methods, and replicated in external datasets for both venous thromboembolism and long COVID. Downstream analyses using gene-specific instruments, along with protein and gene expression data, suggested the protease-activated receptor 1 (PAR-1) as a potential molecular contributor to long COVID. These findings provide human genetic evidence implicating thromboembolism in long COVID pathogenesis.

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