Temporal changes in biomarkers of neutrophil extracellular traps and NET‐promoting autoantibodies following adenovirus‐vectored, mRNA, and recombinant protein COVID‐19 vaccination

Abstract

AbstractNeutrophil extracellular traps (NETs) play a role in innate pathogen defense and also trigger B‐cell response by providing antigens. NETs have been linked to vaccine‐induced thrombotic thrombocytopenia. We postulated a potential link between NET biomarkers, NET‐promoting autoantibodies, and adverse events (AEs) after COVID‐19 vaccine boosters. Healthy donors (HDs) who received ChAdOx1‐S (A), mRNA‐1273 (M), or recombinant protein (MVC–COV1901) vaccines at the National Taiwan University Hospital between 2021 and 2022 were recruited. We measured serial NET‐associated biomarkers, citrullinated‐histone3 (citH3), and myeloperoxidase (MPO)‐DNA. Serum citH3 and MPO‐DNA were significantly or numerically higher in HDs who reported AEs (n = 100, booster Day 0/Day 30, p = 0.01/p = 0.03 and p = 0.30/p = 0.35, respectively). We also observed a positive correlation between rash occurrence in online diaries and elevated citH3. A linear mixed model also revealed significantly higher citH3 levels in mRNA‐1273/ChAdOx1‐S recipients than MVC‐COV1901 recipients. Significant positive correlations were observed between the ratios of anti‐heparin platelet factor 4 and citH3 levels on Booster Day 0 and naïve and between the ratios of anti‐NET IgM and citH3 on Booster Day 30/Day 0 in the AA‐M and MM‐M group, respectively. The increased levels of citH3/MPO‐DNA accompanied by NET‐promoting autoantibodies suggest a potential connection between mRNA‐1273/ChAdOx1‐S vaccines and cardiovascular complications. These findings provide insights for risk assessments of future vaccines.