Coagulation and inflammatory response after intramuscular or intradermal mRNA-1273 SARS-CoV-2 vaccine – secondary analysis of a randomized trial

Introduction Fractional dosed intradermal vaccination produces antibody concentrations above the proposed proxy for protection against severe disease as compared with intramuscular vaccination and may be associated with a decreased prothrombotic effect. Objectives To assess changes in coagulation following standard dosed intramuscular or fractional dosed intradermal (1/5th of intramuscular) mRNA-1273 SARS-CoV-2 vaccine and to determine the association between the inflammatory response and coagulation. Methods This study was embedded in a randomized controlled trial assessing the immunogenicity of an intradermal fractional dosed mRNA-1273 vaccine. Healthy participants, aged 18-30 years, were randomized (2:1) to receive either two doses of intradermal or intramuscular vaccine. Blood was drawn prior to first and second vaccination dose, one and two weeks after the second dose. The outcomes were changes in coagulation parameters (primary endpoint peak height of the thrombin generation curve) and inflammation (high sensitive-CRP). Results 123 Participants were included (81 intradermal; 42 intramuscular). Peak height increased after vaccination, (intramuscular 28.8 nmol; 95%CI: 6.3, 63.8; intradermal 17.3 nmol; 95%CI:12.5, 47.2) and recovered back to baseline within two weeks. Intramuscular vaccination showed a higher inflammatory response compared with intradermal vaccination (extra increase hs-CRP: 0.92 mg/L; 95%CI 0.2, 1.7). Change in Endogenous Thrombin Potential was associated with change in hs-CRP (Beta 28.0; 95%CI 7.6, 48.3). Conclusions A transient increase in coagulability after mRNA-1273 SARS-CoV-2 vaccination occurred, which was associated with the inflammatory response. While intradermal administration showed antibody concentrations above the proposed proxy for protection against severe disease, it was associated with less systemic inflammation. Hence, intradermal vaccination may be safer.