Serum HDL subfractions are impaired by COVID-19 vaccine in patients with thymic epithelial tumors

Patients with thymic epithelial tumors (TET), who have a high risk of developing immunological disorders such as immunodeficiency and autoimmunity, were included among frail patients eligible for the COVID-19 vaccinal program. We previously found an increase of serum biomarkers of inflammation in 25 of 44 (56,8%) TET patients after the second dose (T2) of mRNA vaccine (BNT162b2 from Pfizer-BioNTech), although none developed immune-related complications at this time point. In this study we have investigated the metabolic process of high-density lipoproteins (HDL) that are among the main players in inflammatory and immune modulation. To verify the impact of the vaccine on HDL metabolism in TET patients, we prospectively evaluated serum HDL and HDL subfractions at baseline and T2. Among the 45 TET patients, we observed two different trends: 24 ones (53.3%, subgroup 1) showed a significant decrease of serum small HDL (p < 0.0001) class and/or HDL 10 subfraction (HDL 10) (p < 0.0001) at T2 as compared to baseline values (T0), the other 21 patients (subgroup 2) did not show significant variations. Serum values of small HDL class in subgroup 1 at T2 were inversely correlated with serum interleukin (IL)-6, activated T lymphocytes and regulatory T cells. These findings suggested that the COVID-19 vaccine-related inflammation induces the HDL remodeling with a reduction of anti-inflammatory small HDL class. Further studies need to clarify why the vaccine causes inflammation in about 50% of TET patients and whether such response is peculiar to COVID-19 vaccine or if it would be induced also by other mRNA vaccines.