Genetics Played Role in Rare Blood Clots Linked to COVID-19 Vaccines, Researchers Find

Rare but deadly blood clots tied to J&J and AstraZeneca's vaccines were caused by an autoimmune reaction that some people are predisposed to, researchers found.

Rare but deadly blood clots tied to Johnson & Johnson and AstraZeneca Plc’s Covid-19 shots were caused by an autoimmune reaction that some people are predisposed to, researchers found, a discovery that they say will shape development of future vaccines.

Adenovirus-based vaccines, like the J&J and AstraZeneca shots that were later pulled from the market, contain a component that, in genetically susceptible people, can trigger the production of unusually structured antibodies against a protein involved in blood clotting, scientists said Wednesday in a letter to the New England Journal of Medicine. Researchers plan to identify the culprit and then try to remove it using genetic engineering.

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An extremely similar deleterious antibody response occurs in susceptible patients after infection with adenoviruses, which often infect the airways and lead to cold-like symptoms, the study found. It’s not known how many people may be susceptible to the complication, said Tom Gordon, head of immunology at Flinders University in South Australia, whose molecular sleuthing led to the finding.

The immune reaction linked to the shot is “a new disease,” he said in an interview. Hematologists and intensive care specialists are likely to spot more cases as they become familiar with it, he said.

“It’s a kind of autoimmunity where we know the trigger,” said immunologist James McCluskey, assistant vice chancellor of the University of Melbourne, who wasn’t involved in the research. “That’s unusual. In most cases we never get a handle on the trigger.”

Vaccines withdrawn

Out of more than 18 million people who received the single-dose J&J vaccine, 60 cases of the clotting disorder were reported and nine people died, according to the Yale School of Medicine. 

A small number of clot-related deaths tied to the AstraZeneca vaccine led to its withdrawal or restriction in Denmark, Norway and other countries in 2021. The complication occurred in about 2-3 people per 100,000 vaccinated with the Astra shot under age 60 in Australia, where it hasn’t been available since March 2023. The European Commission withdrew the marketing authorization for the immunization in March 2024.

“AstraZeneca welcomes any further examination of the possible underlying mechanism of thrombosis with thrombocytopenia syndrome (TTS), given that, despite extensive investigation, we do not yet understand the mechanism that can in very rare cases be a trigger for TTS,” a spokesperson for the company said.

J&J also said it supports research that helps guide development of safe and effective vaccines. 

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“More data are needed to fully understand potential factors that may be associated with this rare event, including its potential relationship with adeno- and other viruses, to draw appropriate conclusions about the underlying pathogenesis,” the company said in an email. 

Both shots played an important role in vaccine programs during the early stages of the pandemic. One analysis found the Astra vaccine saved an estimated 6.3 million lives in 2021.

The mRNA vaccines made by the Pfizer Inc.-BioNTech SE partnership and Moderna Inc. were later found to be more effective at protecting against Covid and have been updated to tackle more recent virus variants.