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Scientists say they now know why AstraZeneca’s COVID-19 vaccine may cause blood clots. 

AstraZeneca’s clinical trials last year and its subsequent vaccine rollout earlier this year were clouded by rare, but sometimes deadly, blood clots. After one participant in the clinical trials experienced neurological symptoms, countries around the world put their AstraZeneca trials on pause. Then, when two Austrians experienced blood clotting after vaccination, the European Union temporarily suspended the use of the vaccine. Although the vaccine is now widely used around the world, including in Canada, India, and throughout Europe, the United States has not approved it. 

In a new Science Advances study, researchers say they have found the mechanism that triggers those potentially fatal blood clots. AstraZeneca, like Johnson & Johnson, uses an adenovirus vector in its COVID vaccine to deliver coronavirus immunity instructions to human cells. AstraZeneca’s vaccine adenovirus sometimes binds to a protein in the blood named “platelet factor 4.” That binding can trigger a reaction in which immune cells start to attack the protein, causing clotting, or what clinicians call vaccine-induced immune thrombotic thrombocytopenia (VITT).

[Related: What went wrong with AstraZeneca’s COVID vaccine data?]

“We’ve been able to prove the link between the key smoking guns of adenoviruses and platelet factor four,” Alan Parker, a co-author of the new paper who studies virotherapies at Cardiff University in Wales, told BBC News. But he added that uncovering exactly how that binding causes clumps to form will require further research—“what we have is the trigger, but there’s a lot of steps that have to happen next.”

AstraZeneca reminded The Washington Post that while the vaccine may induce clotting in rare occurrences, blood clots are actually more likely to happen in people with COVID-19 infections. “Although the research is not definitive, it offers interesting insights,” the company added, “and AstraZeneca is exploring ways to leverage these findings as part of our efforts to remove this extremely rare side effect.”

VITT has been linked to 73 deaths out of nearly 50 million AstraZeneca doses in the United Kingdom, according to the UK Health Security Agency. Meanwhile, the agency added, the vaccine has helped prevent more than 80,000 deaths. 

Though the benefits of the AstraZeneca vaccine may still far outweigh the risks of blood clots, understanding the mechanism of this potentially severe side effect is important, Parker said in a statement. “Establishing a mechanism could help to prevent and treat this disorder,” he said. Future scientists who understand how these rare side effects occur could create even safer iterations of these drugs and “turn the tide on this global pandemic.”

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