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. 2026 Jan 9:12:1690764.
doi: 10.3389/fmed.2025.1690764. eCollection 2025.

Genetic patterns related to von Willebrand factor: implications on the need for mechanical ventilation, severity, and death in COVID-19

José López Castro  1 , Silvia Diz-de Almeida  2   3   4 , Manuel L López Reboiro  1 , Cristina Sardiña González  1 ; SCOURGE Cohort Group; Jose A Riancho  5   6   7 , Augusto Rojas-Martinez  8 , Pablo Lapunzina  9   10 , Carlos Flores  11   12   13   14 , Raquel Cruz  15   3   4   16 , Angel Carracedo  15   3   4   16
Collaborators, Affiliations

Genetic patterns related to von Willebrand factor: implications on the need for mechanical ventilation, severity, and death in COVID-19

José López Castro et al. Front Med (Lausanne). .

Abstract

Background: Elevated levels of Von Willebrand Factor (VWF) have been associated to an increased need of mechanical ventilation and higher mortality risk in COVID-19 patients, but the hypothesis of a shared genetic background has not been explored.

Methods: Common and low-frequency genetic variants belonging to the VWF, FVIII, and ADAMTS13 genes were tested for association with clinical variables related to severe COVID-19 disease in 9,371 European and 3,495 Latin-American patients. Gene–environment and gene–gene interactions were also explored.

Results: A variant in the VWF gene was associated to the need of invasive mechanical ventilation (IMV) in the Latin-American population. Gene–gene interaction models pointed to an interaction between ADAMTS13 and VWF genes.

Conclusion: Although we did not find significant associations among Europeans, we identified a low-frequency variant belonging to the VWF gene associated with the need of IMV in Latin-Americans.

Keywords: COVID-19 severity; VWF gene; admixed population; invasive mechanical ventilation; von Willebrand factor.

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Conflict of interest statement

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author CF declared that they were an editorial board member of Frontiers at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
Graphical summary of MDR results for (A) European cohort and IMV, and (B) LA cohort and PT. Graphical model (left) and entropy graph (right). The graphical model (left) is a summary of variable combinations associated with high risk genotypes (dark shading) and with low risk genotypes (light shading), along with the corresponding distribution of cases (left bars in boxes) and controls (right bars in boxes). The entropy graph (right) describes the proportion of entropy that is explained by each SNP or pairwise combination within our study population. Schematic coloration used in the visualization tools represents a continuum from synergy (red or orange for strong and moderate) to redundancy (green and blue), whereas positive and negative values correspond to positive and negative interaction, respectively.
See this image and copyright information in PMC

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