PB0088 - Alterations in thrombin generation after SARS-CoV-2 vaccination and the relation with inflammation

Background: In the first months in which SARS-CoV-2 vaccines were administered, thrombotic events following vaccination were reported. However, reports on the effect of SARS-CoV-2 vaccination various coagulation parameters have shown contradictory results.

Aims: To assess changes in coagulation parameters following intramuscular (IM) or intradermal (ID) SARS-CoV-2 primary immunization using the mRNA-1273 LPN (Moderna) vaccine and to assess the association between potential coagulation changes and the inflammatory response.

Methods: This study was embedded in a randomized trial studying the non-inferiority of ID fractional dose administration of the Moderna vaccine [Roozen, MedRxiv 2021]. Healthy unvaccinated participants, 18-30 years, with no history of COVID-19, were randomized between 1/5th fractional dose ID and standard dose IM. Informed consent was obtained and this study protocol was approved by the local medical ethical committee. Blood was drawn at baseline (prior to vaccination; Day(D)1) and one week after the second dose (D36). Changes in coagulation parameters (thrombin generation (TG); primary endpoint Peak height) and the inflammatory response (hsCRP) were assessed between both timepoints using linear regression analysis.

Results: The analyses included 123 participant. Peak height increased after vaccination, especially in the IM group (table 1). Other parameters of thrombin generation also indicated an increased coagulability after vaccination. HsCRP increased only after IM vaccination (table 2). There was no association between the change in peak height and the change in hsCRP (Beta 1.6; 95%CI -3.5 – 6.6). However, change in several secondary TG endpoints were associated with change in hsCRP (e.g., ETP: Beta 28; 95%CI 7.6-48.3). IgG binding antibodies against SARS-Cov-2 spike and RBD proteins were similar in ID and IM vaccinated participants.

Conclusion(s): These results indicate an increase in coagulability after SARS-CoV-2 vaccination, which was associated with the inflammatory response. While ID administration induced a similar efficacy as IM administration, ID administration was associated with less thrombin activation and inflammation.