Adenovirus-based techniques (such ChAdOx1 nCov-19) are one of the unique platforms used for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines, which are based on a variety of different viruses. A new side effect of SARS-CoV-2-targeted adenovirus vaccinations has recently been identified: immunological thrombocytopenia, either alone or in conjunction with thrombosis (then termed VITT).

Low platelet counts and, in the case of VITT, platelet-activating platelet factor 4 antibodies resembling heparin-induced thrombocytopenia were the hallmarks of the condition, which results in a prothrombotic state with clot formation at odd anatomic locations. Following ChAdOx1 nCov-19 immunization, researchers found antiplatelet antibodies targeting platelet glycoprotein receptors in 42% of patients with isolated thrombocytopenia (n=26) and 30% with established VITT (n=27), showing widespread antiplatelet autoimmunity in both clinical entities. They examined potential pathways of these platelet-targeted autoimmune responses that resulted in thrombocytopenia using in vitro and in vivo models. They demonstrated that ChAdOx1 nCov-19 injection administered intravenously (IV) but not intramuscularly, causes platelet-adenovirus aggregation formation and platelet activation.

Following IV injection, the spleen’s macrophages phagocytosed these aggregates, and platelet remnants are discovered in the marginal zone and follicles. A strong B-cell response with the appearance of circulating antibodies attaching to platelets occurs next. Their research advances the knowledge of platelet-related side effects following ChAdOx1 nCov-19 treatment and sheds insight on inadvertent IV injection as a possible platelet-targeted autoimmune mechanism.

Therefore, one potential defense against platelet-associated diseases following immunization would be to avoid IV injection while providing adenovirus-based vaccinations.