Thrombocytopenia and splenic platelet directed immune
responses after intravenous
ChAdOx1 nCov-19 administration.
Summary paragraph
Vaccines against SARS-CoV-2 are based on a range of novel vaccine platforms, with adenovirus-based approaches (like ChAdOx1 nCov-19)
being one of them. Recently a rare and novel complication of SARS-CoV-2 targeted adenovirus vaccines has emerged:
•
Thrombosis with
•
Thrombocytopenia syndrome (TTS).
TTS is characterized by low platelet counts, clot formation at unusual anatomic sites and platelet-activating PF4-polyanion antibodies
reminiscent of heparin-induced thrombocytopenia.
Here, we employ in vitro and in vivo models to characterize the possible mechanisms of this platelet-targeted autoimmunity.
We show that intravenous but not intramuscular injection of ChAdOx1nCov-19 triggers platelet-adenovirus aggregate formation and platelet
activation. After intravenous injection, these aggregates are phagocytosed by macrophages in the spleen and platelet remnants are found in
the marginal zone and follicles. This is followed by a pronounced B-cell response with the emergence of circulating antibodies binding to platelet.
Our work contributes to the understanding of TTS and highlights accidental intravenous injection as potential mechanism for
post-vaccination TTS.
Hence, safe intramuscular injection, with aspiration prior to injection, could be a potential preventive measure when administering
adenovirus-based vaccines.