Countries of the world have been racing one another, trying to develop and distribute vaccines for COVID-19. In this whirlwind of activity, we’ve focused on learning more about this new virus, seen new technologies and techniques used to create a vaccine, and experienced faster-than-normal developments and approvals of medicines, all in the name of combatting this novel coronavirus.
While we marvel at the medical expertise used to respond so quickly to a global pandemic, we can also wonder whether we have traded one danger for another. Recently, regulators in the EU, U.S., and elsewhere have expressed concerns over the AstraZeneca and Johnson & Johnson (J&J) vaccines, regarding the same problematic side effect: an unusual blood clotting disorder.
These concerns have caused a lot of confusion for healthcare providers and patients alike. Some have paused distribution on these vaccines to await more information and research out of an abundance of caution, while others continue the use them in their immunization effort, sometimes with added restrictions on who can be given the vaccines.
Throughout the last couple of months, as these concerns have been raised, researchers and regulators have stressed the benefits of the vaccine over the risks. Much of the confusion may be down to the need to act urgently and decisively while using incomplete and perhaps convoluted real-world data. While scientists rush to investigate the link between the vaccines and this rare clotting disorder, regulators are forced to make decisions without knowing the results of these investigations.
What is the scope of the problem?
For both vaccines, this side effect is rare indeed. Out of nearly 7-million doses of the J&J vaccine, and 34-million first doses of AstraZeneca, 8 (0.0000011%) and 222 (0.0000065%) people have suspected or confirmed cases of this disorder (although the exact number of cases is uncertain). These clots resemble a rare reaction to the anticoagulant heparin, a condition called heparin-induced thrombocytopenia (HIT), even though these patients weren’t on the drug.
In patients who use heparin, HIT is thought to be triggered when the heparin binds to a protein called platelet factor 4. This stimulates an immune response that ultimately results in the release of clot-promoting material. The question is what could be triggering this response in absence of heparin.
Because there have been so few cases, researchers have not been able to identify specific high-risk categories, although a disproportionate number of these cases have affected women. However, this could be the result of many countries prioritizing vaccination for healthcare workers, who are predominantly female.
Dr. Andreas Greinacher, a clotting expert from the University of Greifswald, lead a study that offers one explanation for the rare reaction. The AstraZeneca and J&J vaccines are adenovirus-based vaccines. Greinacher speculates that some of the billions of virus particles administered in each dose might break apart. This would release a bit of negatively charged DNA that can bind to the positively charged platelet factor 4 protein. This, in turn, triggers an immune response from the body which can lead to the formation of more dangerous clots. The teams involved in producing this study are calling this syndrome, vaccine-induced immune thrombotic thrombocytopenia (VITT).
Researchers at the University of Oxford conducted a large study looking at the risks of developing blood clots in the brain from COVID-19 compared to the vaccines. People who had COVID-19 were 8-10 times more likely to develop clots than people who had taken the vaccine, and about 100 times more likely than people who neither received the vaccine nor were infected with COVID-19.
What is being done?
Researchers and regulators are developing different mitigation strategies to reduce the risks. Broadly, researchers are starting to recommend people under 30 should be offered an alternative vaccine. Researchers in the European Union are also investigating halving the dose of the AstraZeneca vaccine. Regulators are also using the time created by these pauses to educate healthcare providers and patients regarding the newly discovered risks and how to effectively treat them.
Throughout this process, researchers and health authorities have continuously stressed that the benefits of the vaccines outweigh the risks. Science is an ongoing process. As new data comes to light, the most we can do is incorporate the new data and adjust our efforts accordingly. These pauses don’t necessarily mean anything is wrong, it’s just the scientific process working as it should.