Publication date: Dec 01, 2025
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 cD7 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.
| Concepts | Keywords |
|---|---|
| Covid | COVID-19 |
| Genetic | Female |
| Implicating | Humans |
| Thromboembolism | Male |
| Middle Aged | |
| Polymorphism, Single Nucleotide | |
| Risk Factors | |
| Venous Thromboembolism | |
| White People |
Semantics
| Type | Source | Name |
|---|---|---|
| disease | MESH | thromboembolism |
| disease | MESH | long COVID |
| disease | MESH | SARS-CoV-2 infection |
| pathway | REACTOME | SARS-CoV-2 Infection |
| disease | MESH | inflammation |
| disease | MESH | venous thromboembolism |
| disease | MESH | Genetic Predisposition to Disease |