New genetic evidence suggests that people with an inherited tendency towards blood clots may be at higher risk of developing long COVID, strengthening theories that abnormal clotting plays a role in persistent symptoms after SARS-CoV-2 infection.
In one of the largest genetic studies of long COVID to date, researchers found that genetic variants linked to venous thromboembolism were also associated with a higher likelihood of long-term post-COVID illness, independent of how severe the initial infection was.
Testing Clotting Risk Genes
Long COVID is characterised by a wide range of symptoms affecting multiple organs, including fatigue, breathlessness and cognitive problems, lasting weeks or months after acute infection. While ongoing inflammation and microvascular damage have been proposed as underlying mechanisms, direct evidence in humans has been limited.
To address this, researchers analysed data from the Long COVID Host Genetics Initiative, including 3,018 people with long COVID and nearly one million controls. They examined whether genetic variants known to increase the risk of venous thromboembolism – a condition involving blood clots in the veins – were also associated with long COVID. Using genetic risk scores, the team assessed lifelong predisposition to clotting, reducing the influence of confounding factors that affect observational studies.
Higher Genetic Risk, Higher Odds
The analysis showed a clear association between clotting risk and long COVID. Each unit increase in the log odds of genetically predicted venous thromboembolism risk was linked to a 21% increase in the odds of developing long COVID. This effect estimate was statistically robust, with a 95% confidence interval of 1.08 to 1.35 and a P value of 1.2 × 10⁻³.
Importantly, the association was independent of acute COVID-19 severity, suggesting that clotting-related mechanisms may contribute to long COVID even in people who did not experience severe initial illness. The findings held up across multiple sensitivity analyses and were replicated in external datasets, strengthening confidence in the results.
Reference
Schuermans A et al. Human genetics implicate thromboembolism in the pathogenesis of long COVID in individuals of European ancestry. 2025;4:1662-76.
