COVID-19 associated coagulopathy (CAC), characterized by endothelial dysfunction and
hypercoagulability, evokes pulmonary immunothrombosis in advanced COVID-19 cases.
Elevated von Willebrand factor (vWF) levels and reduced activities of the ADAMTS13
protease are common in CAC. Here, we aimed to determine whether common genetic variants
of these proteins might be associated with COVID-19 severity and hemostatic parameters.
A set of single nucleotide polymorphisms (SNPs) in the vWF (rs216311, rs216321, rs1063856,
rs1800378, rs1800383) and ADAMTS13 genes (rs2301612, rs28729234, rs34024143) were
genotyped in 72 COVID-19 patients. Cross-sectional cohort analysis revealed no association
of any polymorphism with disease severity. On the other hand, analysis of variance
(ANOVA) uncovered associations with the following clinical parameters: (1) the rs216311
T allele with enhanced INR (international normalized ratio); (2) the rs1800383 C allele
with elevated fibrinogen levels; and (3) the rs1063856 C allele with increased red
blood cell count, hemoglobin, and creatinine levels. No association could be observed
between the phenotypic data and the polymorphisms in the ADAMTS13 gene. Importantly,
in silico protein conformational analysis predicted that these missense variants would
display global conformational alterations, which might affect the stability and plasma
levels of vWF. Our results imply that missense vWF variants might modulate the thrombotic
risk in COVID-19.
