Published
12 December 2024
  • Journal article

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

Authors
Schuermans, Art; 
Verstraete, Andreas; 
Lammi, Vilma; 
Nakanishi, Tomoko; 
Ardissino, Maddalena; 
Van den Eynde, Jef; 
Sun, Benjamin B.; 
Georgakis, Marios K.; 
Guillen-Guio, Beatriz; 
Wain, Louise V.; 
Brightling, Christopher E. ; 
van Weyenbergh, Johan ; 
Lewandowski, Adam J.; 
Raman, Betty ; 
Zeberg, Hugo ; 
Ollila, Hanna M.; 
Burgess, Stephen; 
Natarajan, Pradeep; 
Honigberg, Michael C.; 
Freson, Kathleen; 
Vanassche, Thomas; 
Verhamme, Peter; 
The PHOSP-COVID Collaborative Group
Source
MedRXiv

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 ( n cases =3,018; n controls =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 =1.2×10 -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.

Rights

The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.

Cite as

Schuermans, A., Verstraete, A., Lammi, V., Nakanishi, T., Ardissino, M., Van den Eynde, J., Sun, B., Georgakis, M., Guillen-Guio, B., Wain, L., Brightling, C., van Weyenbergh, J., Lewandowski, A., Raman, B., Zeberg, H., Ollila, H., Burgess, S., Natarajan, P., Honigberg, M., Freson, K., Vanassche, T., Verhamme, P. & The PHOSP-COVID Collaborative Group 2024, 'Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry'. To be published in MedRXiv [Preprint]. Available at: https://doi.org/10.1101/2024.05.17.24307553

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Topics
Coronavirus (COVID-19)
Keywords
COVID-19 Pandemics Long term conditions Genomics Long term Covid syndrome
Publisher
MedRxiv
Source repository
University of Glasgow
Last updated: 16 December 2025
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