Rare blood clots discussed

Nature has an article about that rare, but sometimes deadly, AstraZeneca blood clotting side effect I still have to have a tiny concern about for another couple of weeks:    

Something in the vaccine or the body’s response to it must be binding to PF4 — but what? VITT has been linked to two COVID-19 vaccines, both of which use disabled adenoviruses as a ‘vector’ to shuttle a gene encoding a coronavirus protein, called spike, into human cells. Once there, the gene is expressed and the protein is made. The immune system detects spike and generates antibodies against it that are crucial for protection against coronavirus infection.

Some researchers have proposed that impurities in the vaccines left over from the manufacturing process — such as snippets of DNA floating around in the solution, or proteins in the broth used to grow the virus — are interacting with PF4 to generate the clumps that are then targeted by antibodies⁶.

Others think the culprit could be the adenovirus itself. Previous work has shown that adenoviruses can bind to platelets and trigger their depletion in mice⁷. It’s conceivable that those mice might also have developed clots if they had been followed for longer, says Maha Othman, who studies blood clotting at Queen’s University in Kingston, Canada, and was lead author of the study.

Before the COVID-19 pandemic, adenovirus-based vaccines were being developed against infections such as HIV and Ebola, but had not yet been used in large populations. There have been no reports that these vaccines produced a VITT-like condition; however, they were not tested in nearly as many people as have received the Oxford–AstraZeneca COVID-19 vaccine.

 Haematologist Mitesh Borad at the Mayo Clinic in Phoenix, Arizona, and his colleagues have analysed the structure of the chimpanzee adenovirus used in the Oxford–AstraZeneca vaccine and determined that it has a strong negative charge. Molecular simulations suggest that this charge, combined with aspects of the virus’s shape, could allow it to bind to the positively charged PF4 protein⁸. If so, it could then set off a cascade much like the rare reaction to heparin, says Borad, although it remains to be seen whether this happens.

Even if the adenovirus is to blame, Borad says he would not advocate that vaccine developers stop using adenoviruses in vaccines. Some adenoviruses could be engineered to reduce their negative charge, he says, and some are less negatively charged than others; the Ad26 adenovirus used in the J&J COVID-19 vaccine does not have as much of a charge as the chimpanzee virus, which might explain why VITT seems to be less common in recipients of the J&J vaccine. And so far, no link to VITT has been reported for the Sputnik V COVID-19 vaccine, which uses both Ad26 and another adenovirus called Ad5 that has still less negative charge, he adds.

There are other theories, explained in the article, but I have probably copied as much as I should.