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

Dec 16, 2025Nature cardiovascular research

Genetic Links Between Blood Clots and Long COVID in People of European Descent

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Long Covid on OpenScience ↗PubMed ↗DOI ↗

Abstract

Each unit increase in the log odds of genetically predicted venous thromboembolism risk was associated with 1.21-fold odds of long COVID.

The study included data from 3,018 individuals with long COVID and 994,582 controls.
The association between thromboembolism-related genetic variants and long COVID was independent of the severity of acute COVID-19.
Findings were validated through various sensitivity analyses and in external datasets.
Gene-specific analyses indicated that the protease-activated receptor 1 (PAR-1) may play a role in the development of long COVID.
These results suggest a potential link between thromboembolism mechanisms and long COVID.

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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. In this study, we tested the association of thromboembolism-related genetic variants with long COVID in the Long COVID Host Genetics Initiative (n = 3,018; n = 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% confidence interval (CI): 1.08-1.35; P = 1.2 × 10). This association was independent of acute COVID-19 severity, was robust across various sensitivity analyses and was replicated in external datasets. 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 shared pathogenetic pathways in thromboembolism and long COVID. cases controls -3