Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT) is a rare complication associated with adenoviral vector-based COVID-19 vaccines. It is characterized by thrombosis, thrombocytopenia, and anti-PF4 antibodies up to 42 days after vaccination. Evidence suggests that genetic factors may influence susceptibility to the syndrome, but specific data are still scarce.

To investigate rare genetic variants related to the pathophysiology of VITT in individuals vaccinated with ChAdOx1 nCoV-19.

Confirmed cases of VITT were included between 2022 and 2023. Whole genome sequencing and bioinformatics analysis were performed on a dedicated platform, applying quality control criteria, filtering, and variant prioritization. Genetic panels targeting Inborn Errors of Immunity and VITT pathophysiology were used, with subsequent functional enrichment analysis in biological pathway databases.

Thirteen VITT cases were analyzed using adequate-quality genomic DNA. After filtering, rare variants were identified across genes in both panels. Initial functional analysis revealed enrichment in pathways associated with prothrombotic and proinflammatory mechanisms, such as platelet activation, the coagulation cascade, and innate immune signaling.

Variations in VITT incidence worldwide during mass vaccination against COVID-19 are believed to be due to demographic, environmental, and genetic predisposition differences (1). Previous molecular studies have demonstrated the oligoclonality of antibodies anti-PF4 in VITT (2). Our preliminary results suggest that rare genetic variants in genes linked to immunity and hemostasis may be involved in VITT susceptibility. Further analyses, including sample expansion, will be needed to confirm and investigate these findings.