A recent study published in Scientific Reports suggests that autoantibodies targeting protein S may explain rare cases of coagulopathy observed following COVID-19 vaccination. The research, which compared patients experiencing coagulation-related adverse events following immunization (AEFIs) with healthy controls and individuals with other AEFIs, offers a potential mechanism for these rare but serious complications.
Study Design and Methodology
The exploratory study, conducted as part of the SWEDEGENE project, analyzed samples from individuals who experienced AEFIs after receiving COVID-19 vaccines, including Comirnaty (Pfizer), Spikevax (Moderna), and Vaxzevria (AstraZeneca). Causality assessment for AEFIs was performed according to World Health Organization (WHO) criteria. The study involved two subsets of patients, with the second subset including both newly-received samples and unthawed samples from the first subset. Autoantibody responses were assessed using a multiplex bead-based immunoassay and confirmed via ELISA. Functional analyses were also performed to assess the physiological impact of the identified autoantibodies.
Key Findings
The researchers identified autoantibodies against several coagulation-related proteins, including protein S, in patients with coagulation-related AEFIs. Further analysis confirmed the presence of protein S autoantibodies in a subset of these patients. Functional assays indicated that these autoantibodies could impair protein S activity, potentially contributing to the observed coagulopathy. The study defined ‘coagulation-related AEFI’ as patients with thrombosis, bleeding, thrombocytopenia or myocardial/cerebral infarction.
Autoantibody Detection Methods
The study employed a combination of bead-based immunoassays and in-house/commercial ELISA assays to detect autoantibodies. The bead-based assay screened for autoantibodies against coagulation-related proteins like Factor V, Protein S, Protein C, Prothrombin, PF4, ApoH, and Antithrombin III. Positive results were confirmed by ELISA, demonstrating elevated responses relative to healthy blood donors and patients with myocarditis. Commercial assays were used to detect antibodies against PF4-polyanion complexes (PF4C) and antiphospholipid antibodies.
Implications and Future Directions
These findings suggest that the development of autoantibodies against protein S may be a contributing factor in the rare cases of coagulopathy observed following COVID-19 vaccination. Further research is needed to fully elucidate the mechanisms underlying this phenomenon and to identify individuals at higher risk of developing these autoantibodies. The study highlights the importance of continued monitoring and investigation of AEFIs to improve vaccine safety and inform clinical management strategies. According to the original article, the study was approved by the Swedish Ethics Review Board (ethical permit: #2021-06262-01) and all recruitment/analytical processes conformed to the Declaration of Helsinki.
