Why some COVID vaccines provoked blood clots while others didn’t

Researchers have narrowed in on a reason why the AstraZeneca COVID-19 vaccine causes blood clots in rare cases, while the Pfizer vaccine doesn’t.

The Australian Government says the rates of blood clots per vaccine are around 2 or 3 per 100,000. There were nine confirmed deaths from the vaccine as of December 2021.

A study in Cell Reports Medicine used a technique called multinomics to investigate how people’s immune systems responded after either getting the adenovirus-based AstraZeneca vaccine, or the mRNA-based Pfizer vaccine.

For more on the differences between the vaccines: Explainer: COVID vaccine ingredients: what’s in each jab?

The researchers, who are based at the South Australian Health and Medical Research Institute (SAHMRI) and Flinders University, took blood samples from 102 adult volunteers, both immediately after, and 28 days after, receiving a dose of either vaccine.

The blood samples were all taken while there was no community transmission of COVID-19 in South Australia, where all volunteers were based. This ensured that the immune responses they tracked were influenced only by the vaccines, not COVID infection.

“After the first dose, we were surprised to find the Oxford/AstraZeneca vaccine elicits an unexpected memory-like response in the immune system, recognising the vaccine as if it’s something it’s seen before,” says study lead Professor David Lynn, a researcher at SAHMRI and Flinders.

“This response is targeted against the adenovirus vector in the vaccine, not the spike protein, and the intensity of this response correlates with the expression of proteins that act as a precursor to thrombosis, or blood clotting.”

This means in addition to provoking a response against the spike protein on SARS-CoV-2 like it was supposed to, the AstraZeneca vaccine was also provoking an immune response against the adenovirus “packaging” the vaccine used.

“While vaccine-induced immune thrombotic thrombocytopenia (VITT) is an extremely rare side effect associated with the Oxford/AstraZeneca vaccine that none of the participants developed during the study, this research offers a potential explanation for the connection between the Oxford/AstraZeneca vaccine and the cases of VITT that’ve been reported,” says Lynn.

The study also found that two doses of the AstraZeneca vaccine provoked fewer antibodies and certain immune cells than the Pfizer vaccine.

But a third booster dose of an mRNA vaccine rectified this.

Finally, the researchers found that people who reported side effects after a third dose also had better immune responses.

“People who showed symptoms of fatigue and fever immediately after the third dose were more likely to have better T-cell responses. T-cells play a vital role in vaccine efficacy as they can directly kill viral cells,” says Lynn.