Mechanism of COVID-19 adenovirus vaccines’ blood clotting adverse events unveiled by Canadian scientists

In Canada, this reaction has been reported to occur in one of every 60,000 people who received the AstraZeneca vaccine. This publication in Nature describes how unusual vaccine-triggered antibodies stick to components from blood platelets causing them to trigger clot formation. These findings allow for a better diagnosis and treatment of individuals with this clotting disorder, while adding to the literature to work towards safer vaccines in the future.

The COVID-19 adenovirus-based vaccines, namely AstraZeneca and Johnson & Johnson, are associated with a clotting disorder known as vaccine-induced immune thrombotic thrombocytopenia (VITT). Current rapid tests for this disorder lead to many false-negative results; testing also requires time-consuming methodologies.

Key points:

• Samples from five VITT patients were studied; individuals were between 35 and 72 years old and had received either AstraZeneca or Covishield vaccines 14 to 40 days prior to developing clotting disorders (thrombocytopenia and thrombosis).
• The samples revealed that antibodies bound to the platelet protein called platelet factor 4 (PF4) in a unique orientation, which enabled other antibodies and platelets to aggregate, triggering the clotting cascade.
• This particular and unique binding orientation also explains why rapid competition assay tests frequently fail: these uniquely oriented antibodies are not recognized by the internal control antibody used in the test, as those in the test bind to a different region. This information may be useful to improve diagnostic testing.

Despite this rare side effect, viral vector vaccines remain an effective method of conferring protection against SARS-CoV2.