Proteomic signatures of Post-Vaccination/Post-Infection Syndrome (PV/PIS): Insights into immune dysregulation and coagulopathy

During the global rollout of COVID-19 vaccines a subset of individuals reported persistent symptoms following vaccination, with clinical presentations overlapping those of Long COVID requiring individualised treatment decisions. Distinguishing between vaccine-related adverse events and post-infectious sequelae remains challenging, particularly given the possibility of asymptomatic or mild SARS-CoV-2 infection prior to or after vaccination. To avoid this complexity, we define this patient group as presenting with Post-Vaccination/Post-Infection Syndrome (PV/PIS). In this study, we performed a proteomic analysis of plasma from 30 individuals with PV/PIS compared to healthy controls. Using mass spectrometry, we identified significant alterations in coagulation factors, acute phase proteins, and immune response modulators in the PV/PIS group. Notably, elevated levels of serum amyloid A1 and A2, attractin, and coagulation factors X and XI were observed, alongside downregulation of immune-regulatory proteins. These findings suggest that PV/PIS is characterized by persistent immune dysregulation and coagulopathy, with proteomic signatures only partially overlapping those previously reported in prior proteomics analysis on Long COVID samples collected prior to vaccination availability. Our results highlight the complex interplay between immune activation, endothelial dysfunction, and coagulation pathologies in PV/PIS, while also highlighting distinct differences between these systems in Long COVID and PV/PIS, paving the way for more targeted protein research in these conditions.