On Tuesday, the CDC and FDA recommended that states pause the administration of the Johnson & Johnson Covid-19 vaccine after six rare blood clots that were potentially linked to the vaccine were reported. Earlier this week, the European Medicines Association (EMA) reported it was investigating four cases of blood clots related to the Johnson & Johnson vaccine, and the company said in a statement that it would be pausing its rollout into Europe.
These announcements have come on the heels of an ongoing controversy over the AstraZeneca vaccine, which has also been paused or restricted in multiple countries after reports of extremely rare blood clots among people who had received it. Both vaccines use a similar technology, which is distinct from the mRNA vaccines developed by Pfizer and Moderna. Here’s what’s known about the blood clotting risks so far, and how public health experts intend to manage these risks to continue the response against the pandemic.
Though Extremely Rare, It’s Likely The Clots Are Related To The Vaccines
So far, these blood clots are extremely rare. The risk of a blood clot occuring after the Johnson & Johnson vaccine is so far about one in a million, while the risk from the AstraZeneca vaccine has been found to be closer to 1 in 250,000 in the U.K. Both of these risks are far lower than the risk of getting a blood clot from Covid-19 itself, which one paper found occurs in about 20% of Covid-19 patients.
But scientists do have good reason to suspect that the clots are linked to the vaccines. The types of clots that have been reported after vaccination are “extraordinarily unusual and bizarre,” says John Kelton, a researcher at McMaster University in Ontario, occurring in parts of the body that aren’t normally known for experiencing clots. The patients that are getting these blood clots also have low numbers of cells that normally help the body to clot when damaged, called platelets. Low platelets usually means that the body can’t form clots — but in these recently vaccinated patients, clots are popping up in seemingly random areas.
The combination of unusual clots and low platelets is actually one that Kelton first saw about 40 years ago in a disease that’s now called heparin induced thrombocytopenia. It can occur when patients who take heparin, a popular blood thinning medication, spontaneously develop rare blood clots. In rare occasions the same phenomenon has been documented in patients who haven’t taken heparin: low platelets, but unusual clots. It’s an easily identifiable condition, Kelton says, because “this is a very dramatic reaction.” It can also be confirmed through a chemical test.
Kelton and his team recently received eight samples from patients who had gotten blood clots after getting the AstraZeneca vaccine — and one sample in particular stood out. “It was exactly the syndrome that we’ve seen before,” he says.
The Clots May Be Related To The Underlying Vaccine Technologies
Though scientists strongly suspect these vaccines may be linked to this extremely rare clotting disorder, they don’t yet know why. Both vaccines work in a similar fashion: they deliver genetic material to cells that instructs them to create a portion of the coronavirus called the spike protein, which stimulates the immune system to produce Covid-19 antibodies. Additionally, both vaccines deliver those genes to patients using a common cold virus, called an adenovirus, that’s been genetically modified to not make people sick. Similar blood clotting has not been observed in either the Pfizer or Moderna mRNA vaccines, which rely on a different technology.
There are several hypotheses for why these adenovirus vaccines might cause clots, says Maria Sundaram, a postdoctoral researcher at theInstitute for Clinical Evaluative Sciences in Ontario. It could be that the positively-charged particles of viral DNA in the vaccines are breaking apart and attaching to a negatively-charged protein in the body called platelet factor 4. This could potentially induce blood clots to form. But, she says, “that doesn’t seem very likely due to the lab studies we’ve been doing.” Another potential explanation is that the body’s immune system could be triggered to attack this type of vaccine because it recognizes it as a foreign entity in the body.
Still other researchers hypothesize that it’s the adenovirus vector itself that could be causing the clots. While these have been studied for decades, the AstraZeneca and Johnson & Johnson Covid-19 vaccines are the first that have used the technology on a massive scale of millions of people. The only other adenovirus vaccine that is commercially authorized is one for Ebola, also manufactured by Johnson & Johnson, which has only been given to a few hundred thousand people in West Africa — which may not be enough people for the rare clotting effect to be observed.
How Public Health Experts And Vaccine Makers Can Reduce These Rare Risks
If it turns out the rare blood clotting is related to the vaccine’s adenovirus vector, says Paul Offit, Director of the Vaccine Education Center at the Children’s Hospital of Philadelphia, “you might be able down the line to alter that vector” in a way that prevents it from causing blood clots. But, Offit says, that could take months or years of more research.
“If it’s one protein in that vector that’s being produced and you could modify that, maybe,” says Bill Moss, Executive Director of the International Vaccine Access Center at Johns Hopkins. “ But it will really take some more detective work to figure out what components of those vaccines are creating those [clotting] antibodies.”
Researchers like Kelton are already looking into this by requesting more samples from people who have gotten blood clots after getting vaccinated. “We have got the back half of the reaction — we know how it binds to platelets, we’ve studied that for decades,” he says, “what we don’t know is the front end.”
In the meantime, the CDC’s Advisory Committee on Immunization Practices (ACIP) will hold an emergency meeting on April 14th to discuss whether the Johnson & Johnson vaccine rollout should continue to be paused. They might, like other countries in the EU and Canada, recommend that adenovirus vector vaccines only be given to people who are over a certain age. Most of the patients that have gotten these unusual blood clots are young women, so some nations have ordered that only people ages 55 and older can get the AstraZeneca or Johnson & Johnson vaccine.
Sundaram and Kelton both add a note of caution about these patient restrictions, however: The age and gender association in clots could be a red herring. Both scientists pointed out that the majority of people who have received these vaccines, particularly in the EU, are teachers and healthcare workers; and the majority of teachers and healthcare workers are young women. “It’s pretty hard to tell,” if age and gender are risk factors for these blood clots, says Sundaram, particularly since the clots appear so rarely.
Luckily when these rare blood clots do occur they are often easily treated, as long as they are caught early enough. The CDC says that if a patient experiences symptoms including severe headache, leg pain, shortness of breath or abdominal pain within three weeks of getting the Johnson & Johnson vaccine, they should contact their healthcare providers. Often, Kelton says, these clots can be treated in the hospital with blood thinners — though he advises these rare patients stay away from heparin.
Scientists and public health officials have another daunting task going forward: communicating to the public that these pauses are actually a good thing, and shouldn’t make people afraid of the vaccine. “These side effects are extremely rare, so you’re not taking a big risk,” Offit says. Meanwhile, “there’s nothing theoretical” about the risks of Covid-19.
Moss says that numerically, the risk of using these vaccines is much smaller than the reward. “The calculus I think is pretty straightforward,” he says, “the public health messaging is the tricky part. Maintaining trust and confidence is very hard.”