Thrombosis with thrombocytopenia syndrome (TTS) is a rare but potentially severe adverse event following immunization with adenovirus vector-based COVID-19 vaccines such as Ad26.COV2.S (Janssen) and ChAdOx1 (AstraZeneca). However, no case of TTS has been reported in over 1.5 million individuals who received a second immunization with Ad26.COV2.S in the United States. Here we utilize transcriptomic and proteomic profiling to compare individuals who receive two doses of Ad26.COV2.S with those vaccinated with BNT162b2 or mRNA-1273. Initial Ad26.COV2.S vaccination induces transient activation of platelet and coagulation and innate immune pathways that resolve by day 7; by contrast, patients with TTS show robust upregulation of these pathways on days 15-19 following initial Ad26.COV2.S vaccination. Meanwhile, a second immunization or a reduced initial dose of Ad26.COV2.S induces lower activation of these pathways than does the full initial dose. Our data suggest a role of coagulation and proinflammatory pathways in TTS pathogenesis, which may help optimize vaccination regimens to reduce TTS risk.
Aid, Malika; Stephenson, Kathryn E.; Collier, Ai-Ris Y.; Nkolola, Joseph P.; Michael, James V.; McKenzie, Steven E.; and Barouch, Dan H., "Activation of Coagulation and Proinflammatory Pathways in Thrombosis with Thrombocytopenia Syndrome and Following COVID-19 Vaccination" (2023). Cardeza Foundation for Hematologic Research. Paper 75.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Peer Review File_MOESM2_ESM.pdf (43 kB)
Description of Additional Supplementary Files_MOESM3_ESM.pdf (179 kB)
Supplemental Data 1_MOESM4_ESM.xlsx (21 kB)
Supplemental Data 2_MOESM5_ESM.xlsx (9 kB)
Reporting Summary_MOESM6_ESM.pdf (227 kB)
Source Data_MOESM7_ESM.xlsx (101 kB)