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

May 27, 2024medRxiv : the preprint server for health sciences

Genetic links to blood clots in long COVID among people of European background

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Abstract

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

A total of 3,018 individuals were analyzed for the association between thromboembolism-related genetic variants and long COVID.
The association between thromboembolism risk and long COVID was independent of the severity of acute COVID-19.
Results were consistent across various genetic analysis methods and replicated in external datasets.
Gene-specific analyses indicated that protease-activated receptor 1 (PAR-1) may play a role in the development of 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. Here, we tested the association of thromboembolism-related genetic variants with long COVID in the Long COVID Host Genetics Initiative (=3,018;=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;=1.2 × 10). 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. . n n P cases controls -3

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

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