In both cases, the blood clots affect very small numbers of people. Regulators are trying to balance the potential risks of the shots against their overwhelming benefits in fighting the pandemic, which has already killed almost 3 million people around the world.
There are other shots available from Moderna, Pfizer-BioNTech, and more. But supplies are limited, meaning that a decision to stop using the AstraZeneca or J&J shots could delay the global immunization campaign.
To understand the risks and benefits of these vaccines, join us on Thursday, April 15, at 11am ET/ 8am PT for a live discussion hosted by Insider Healthcare Editor Zachary Tracer with reporters Aria Bendix and Dr. Catherine Schuster-Bruce.
When coronavirus vaccines were rolled out to the public, regulators knew they would need to watch out for extremely rare reactions. Although clinical trials had shown the shots to be safe among tens of thousands of people, the world was about to vaccinate tens of millions.
Their vigilance paid off earlier this month when European regulators announced that rare blood clots might be an uncommon side effect of AstraZeneca’s vaccine. Then on Tuesday, US regulators recommended a pause in the distribution of Johnson & Johnson’s vaccine due to six reports of the same type of clot among women who’d received that shot.
AstraZeneca’s and J&J’s vaccines share a platform: Both are viral-vector vaccines, which introduce a coronavirus gene into the body using a genetically engineered common-cold virus, called an adenovirus. Some medical experts are now wondering whether that technology itself could be linked to clotting.
“Why are we seeing these few cases for J&J and AstraZeneca? We don’t know. It just makes sense – hey, maybe, it’s how the vector is introduced, because that’s the biggest difference,” Dr. Vivek Cherian, a hospitalist at the University of Maryland St. Joseph Medical Center, told Insider.
Regulators haven’t discovered the same clotting issues with the Pfizer and Moderna vaccines, which rely on a different technology: mRNA that spurs the body to produce one of the coronavirus’ signature proteins, thereby stimulating an immune response.
But scientists are still trying to figure out why only certain people – mostly young women so far – develop these rare clots, and whether all vector vaccines might trigger the same reaction.
A reaction to the adenovirus?
The particular blood clot in question, central venous sinus thrombosis (CVST), forms in the brain – so it can lead to headaches or stroke. In an average year, this condition occurs in about five people out of every million.
By early April, European medical officials had identified 169 CVST cases out of more than 34 million people in the European Union who’d received AstraZeneca’s shot. That’s still just five cases per million shots – about the rate you’d see in a normal population – so researchers weren’t sure whether the clots were caused by the vaccine.
Regulators also noticed a distinct pattern among all the vaccine-related cases: In addition to CVST, the patients had low levels of platelets – colorless blood cells that help clots form.
“This type of a combination of low platelets and blood clots has been very rarely seen in the past in other situations as an autoimmune phenomenon, but it’s very, very rare,” Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said in a Tuesday briefing.
Before the vaccines were authorized, this combination was primarily seen in association with the blood-thinning drug heparin. In rare cases, people taking the medication develop antibodies that bind to a specific platelet, which can make them more susceptible to clots.
In a study of 11 people who developed clots after receiving AstraZeneca’s vaccine, they all tested positive for antibodies against that same platelet.
“Whether there’s some kind of a reactive mechanism based on the adenovirus, and whether that somehow activates these platelets – that’s what they’re trying to look into,” Peter Gulick, an associate professor of medicine at Michigan State University, told Insider, referring to US and European regulators.
Other vector vaccines may not necessarily have the same blood-clot links
Before AstraZeneca’s and J&J’s shots, only a couple viral vector vaccines had ever been authorized in humans: In 2017, China approved an Ebola vaccine that uses an adenovirus, but that shot was only authorized for emergency use, so relatively few people have ever received it. The US and EU approved another viral vector vaccine for Ebola in 2019, but the shot hasn’t been widely administered, either.
For that reason, it’s hard to know whether blood clots may be a rare issue associated with vector vaccines in general, or if the reaction is just related to the specific adenoviruses used in AstraZeneca’s and J&J’s shots.
It’s also possible, of course, that these clots aren’t associated with vaccines at all.
“I don’t think [clotting is] something that we automatically expect with a vector vaccine,” Namandjé Bumpus, director of the pharmacology and molecular sciences department at Johns Hopkins Medicine, told Insider.
Adenoviruses are usually harmless, Bumpus added: They’re disabled before they’re injected so that they won’t replicate inside the body. They’re also engineered to resemble common, naturally occurring viruses, which on their own don’t cause blood clots.
But the adenoviruses used in vaccines can’t be too common either, because then anyone who’d previously been exposed to them would fight them off before they could trigger an immune response. For that reason, AstraZeneca’s shot uses an adenovirus strain only found in chimpanzees. J&J’s shot, meanwhile, uses a modified human adenovirus that’s not easily recognized by the immune system.
It’s possible, Gulick said, that one particular adenovirus might cause blood clots while another might not. The vaccine dose could matter as well: A 2007 study found that high doses of adenoviral vectors triggered low platelet counts in mice. But that reaction usually occurred within 24 hours after the injection, and people who’ve developed CVST after their AstraZeneca and J&J shots usually did so within two weeks.
This suggests the condition wasn’t triggered by the body’s innate immune response (the one that leads to normal vaccine side effects like fatigue or muscle aches), but instead by the adaptive immune response – the one responsible for churning out antibodies.
It’s too soon to say whether the clots are specific to young women
Most of the CVST cases following AstraZeneca’s shot occurred in women under 60, while all six J&J cases were reported in women between 18 and 48.
Cherian noted that young women have higher levels of estrogen, which makes them more likely to have strong immune responses in general. Gulick, meanwhile, pointed out that women have more T-cell receptors, which can also prompt the immune system to react aggressively to foreign invaders.
“My guess is it lies somewhere in how our immune system is responding in a very, very select set of individuals to that vaccine,” Cherian said.
But Bumpus cautioned against associating the clots with any particular group yet.
“It’s just such a rare event in such a small group,” she said. “Even though it’s a bit tempting to think that it’s specific to a subgroup, we have to be unbiased a little bit and just look at the data.”
Ultimately, she added, it could take years of research to determine why some people developed clots after either shot.
“There are many medicines that we take safely and confidently, that we still all the time – even after decades of use – are learning more and more about their mechanisms and their impact on cells,” Bumpus said. “It’s just with these [vaccines], it’s all unfolding in real time in front of our eyes.”
The remaining 3 children will have to wait for vaccination to be expanded to younger populations.
Getting the Pfizer vaccine to the tiny island would have been a logistical nightmare, BBC Scotland’s Jen Stout reported. The shot, which until recently required ultra-low storage temperatures, would have been very difficult to get on the tiny airplanes and boats that go to the windy territory, part of the Shetland Islands.
The AstraZeneca vaccine, however, could be transported in two-seater airplane in a cold box.
“Fair Isle was one of those areas in the UK where there were no confirmed Covid cases so we thought it was really important to continue that as a statistic moving forward,” the director of health and community care in the area told BBC radio Scotland’s “Good Morning Scotland.”
Fair Isle is the most remote inhabited part of the United Kingdom. It is not connected to the main electricity grid, and has only had reliable electricity since 2018, which comes from a system of solar panels and wind turbines. It is 3 miles long and 1.5 miles wide.
The island is know for its observatory, which watches migratory birds, and its particular style of woolen sweaters.
Alex Penn, Assistant Warden at the Fair Isle Bird observatory, snapped a picture of the tiny island on Monday:
For the first time in the US’s vaccine rollout, regulators have pumped the breaks on an authorized coronavirus shot.
On Tuesday, the Centers for Disease Control and Prevention and the Food and Drug Administration together recommended a temporary pause in the distribution of Johnson & Johnson’s vaccine while regulators investigate six reports of unusual blood clots.
All six of those cases involved women between 18 and 48 who developed central venous sinus thrombosis, an exceedingly rare type of clot in the brain. One of the women died and another is in critical condition.
“Instead of taking away confidence from other vaccines, this should actually inspire further confidence in the oversight of these vaccines and definitely should not deter individuals scheduled for either Pfizer and Moderna vaccines to go through with their appointments,” Dr. Vivek Cherian, an internal-medicine physician in Baltimore, told Insider.
Roughly 68 million American have been fully vaccinated with either Pfizer’s or Moderna’s shot since December, and nearly 185 million doses have been administered in total. In that time, US regulators haven’t discovered any significant safety concerns among people who’ve gotten those vaccines. (The CDC tracks vaccine side effects through a tool called V-safe and healthcare providers are required to report adverse reactions via an online system called VAERS.)
“There’s a lot of close scrutiny of these vaccines,” Peter Gulick, an associate professor of medicine at Michigan State University, told Insider.
He added that Pfizer’s and Moderna’s shots are “months ahead of J&J” in their production and rollout, and regulators have yet to see any red flags. Even his HIV patients, Gulick said, haven’t reported severe reactions.
J&J’s vaccine, by contrast, was introduced more recently: It was authorized in late February and has been administered to just under 7 million Americans so far.
“When you start vaccinating people, you have a much, much, much larger sample size – in the millions,” Cherian said. J&J’s clinical trial, by contrast, had just under 44,000 people. “So when you have these exceedingly rare complications, sometimes you don’t see that until you actually start.”
Pfizer’s and Moderna’s shots carry ‘virtually no risk’ of clotting
J&J’s vaccine hasn’t come close to exceeding these normal background levels yet, with fewer than one CVST case for every 1 million doses reported so far. But researchers have also seen some CVST cases among people who got AstraZeneca’s coronavirus vaccine, which bears many similarities to J&J’s.
Both AstraZeneca’s and J&J’s shot are viral-vector vaccines, which introduce a coronavirus gene into the body using a genetically engineered common-cold virus. Some scientists are wondering whether the platform itself could be linked to clotting.
Pfizer’s and Moderna’s vaccines, on the other hand, rely on mRNA technology, which uses a snippet of the coronavirus’ genome to trigger an immune response.
At an American Medical Association webinar on Tuesday, Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said the US has identified just three CVST cases among the 68 million people who got the double-dose mRNA vaccines.
In a Tuesday statement, Moderna also said it had carried out its own comprehensive analysis and found no association between its shot and CVST or other types of clotting.
“It’s safe to say there’s virtually no risk in individuals who received mRNA-based [vaccines], but we don’t really have that information yet as far as the viral-vector,” Cherian said.
But he added that even with the viral vector vaccines, “far, far less than even 1% of individuals are actually having these side effects.”
By comparison, a November study found that 20% of hospitalized COVID-19 patients developed blood clots in their veins.
The US rollout of Johnson & Johnson’s COVID-19 vaccine is on pause as experts evaluate six cases of severe blood clots in the brain possibly linked to the shots.
It’s unclear if the vaccines lead to these clots or if it’s just a coincidence.
On one hand, the type of blood clot seen in conjunction with another blood condition in the six J&J cases is so rare in the general population its prevalence is unknown. That raises red flags that the shot could play a role.
On another hand, all six cases of post-J&J shot clots were in women between the ages of 18 and 48, a group at higher risk of blood clots anyway.
Similarly, most blood clot cases that occurred after AstraZeneca’s COVID-19 vaccine in Europe were in women under 55. The European Medicines Agency has said the shots themselves weren’t the cause.
Young women are at a higher risk of developing certain types of blood clots regardless of their vaccine status, Mary Cushman, a professor of medicine at the University of Vermont’s Larner College of Medicine, told Insider. Hormonal birth control and pregnancy may play a role in this elevated risk.
Birth control pills and pregnancy both increase the risk of blood clots
Young women are at a relatively high risk for blood clots since they’re most likely to take the birth control pill or get pregnant, which both increase the odds of developing a clot, Cushman told Insider.
Specifically, the US Food and Drug Administration estimates that between 3 and 9 out of 10,000 women who take certain birth control pills will develop a blood clot each year, compared to 1 to 5 women per 10,000 who do not have risk factors for blood clots.
The risk of getting a blood clot as a side effect of the pill is higher than the likelihood of clotting due to the vaccine. Scientists have known about this risk factor for decades, however, it’s still rare, as a recent TikTok video pointed out.
“Millions of women everywhere take the contraceptive pill, and amongst the hundreds of side effects that come with the contraceptive pill – one of which is death – there’s a 6 in 10,000 chance of getting a blood clot,” TikToker alysselizabeth said in the video.
Still, the risk of clotting post-vaccine versus the risk related to birth control isn’t an apples-to-apples comparison. There’s far more data on birth control-associated clots, but a lot of it is flawed and outdated. Plus, the specific type of brain clots seen after J&J vaccine, as well as its presentation with low platelet count, differentiates them from the clots most typical among birth control pill users.
“This is a different clinical entity than blood clots associated with oral contraceptives,” Dr. Melanie Swift, co-chair of the Mayo Clinic COVID-19 Vaccine Allocation and Distribution Work Group, told Insider.
There are other risk factors for blood clots – including COVID-19
Obesity and genetic factors can also increase someone’s risk of developing a blood clot, Cushman said. Physical activity and other healthy lifestyle choices can help manage that risk.
“It’s always really important to stay active, avoid sedentary time, keep to a healthy weight, and have a healthy diet,” Cushman said. “And if you’re using an oral contraceptive, or if you have obesity, maybe just ratchet up your awareness a little bit, but don’t avoid the shot.”
“The bottom line is that the risk of adverse health consequences from COVID-19 far outweighs any risk of the shot,” Cushman said.
Added Swift: “I would tell everyone to have confidence in the vaccine safety monitoring system in the US. What an amazing feat to have detected a signal of only 6 people among millions. … We do not want this time out for one brand of vaccine to stall vaccination efforts overall because that would result in more needless lives lost to the pandemic.”
Up to 80% of people in Sicily are turning down the AstraZeneca vaccine when it is offered, the island’s leader said on Saturday.
Nello Musumeci, Sicily’s president said in a press conference on Saturday that “out of 100 people, 80 say no” to the AstraZeneca vaccine, AFP reported.
A spokesperson for Musumeci later told AFP that the figure was too extreme and that he had meant to say “up to 80%.”
In some cities, like Syracuse, the refusal rate was lower, around 30%, the spokesperson said.
Musumeci said that he understood why people would be concerned about the vaccine, but that Sicilians “have a duty to believe scientists” when they say the vaccine is safe, Giornale di Sicilia reported.
“The only solution is to immunize the Sicilian community,” he said.
The European Medicines Agency (EMA) last week listed unusual blood clots with low platelets as a very rare side effect of the AstraZeneca vaccine. The agency said that the benefits of the shot outweigh the risks.
Germany, France, the UK, and other countries have restricted the use of the vaccine in younger people over concerns about unusual blood clots.
Experts have told Insider that having the shot is still safe and is less risky than flying in a plane. One expert told Insider that the real risk was that vaccine skepticism would rise among those who are offered the vaccine.
Johnson & Johnson’s coronavirus vaccine rollout hit several unfortunate snags this week – some far worse than others.
The New York Times reported on Tuesday that 62 million of the company’s vaccine doses must be checked for contamination, following an error at a Maryland manufacturing plant that already ruined 15 million doses. The plant’s workers accidentally mixed up some vaccine ingredients last month.
The timing of these developments was unfortunate, experts said, but there’s no reason to doubt the shot’s safety yet.
“You don’t want to be fueling unnecessary worries about the safety of vaccines when you’re still seeing an enormous outbreak and death rates all over the world from COVID,” Art Caplan, a bioethicist at New York University, told Insider.
He added that the side effects observed at the US vaccination sites were “absolutely trivial.”
“When you see these clusters [of side effects], they usually are worked out and have no relation to the vaccine,” Arnold Monto, an epidemiologist at the University of Michigan’s School of Public Health, told Insider. Monto chairs the Food and Drug Administration’s Vaccine Advisory Committee, which voted to recommend the Pfizer, Moderna, and Johnson & Johnson shots.
People could get dizzy or nauseous for many reasons
Most of the negative reactions to Johnson & Johnson’s shot occurred within 15 minutes after a person got vaccinated, public-health officials in Colorado, Georgia, and North Carolina reported. In total between the three states, seven people were taken to hospitals for observation. As of Friday, all but one had been released and everyone was expected to fully recover.
Officials haven’t yet pinpointed why these clusters of adverse reactions were identified in such a short time frame. But they’ve emphasized that there’s no reason to be concerned about the shot itself.
In a news release, Georgia’s public health commissioner, Kathleen Toomey, said the state was looking into “what may have caused the reactions, including the conditions at the fairgrounds such as heat and the ability to keep the site cool.”
Caplan said it’s also possible that the people who felt dizzy or nauseous were elderly or had underlying health conditions that may have predisposed them to adverse reactions. And once one site reports a cluster of patient reactions, that makes others more likely to look for them and take swift action.
Whatever the reason, Monto said, the fact that adverse reactions are being reported and investigated shows that local officials are working hard to minimize harm.
“Any pause in vaccination shows that the system is working because we’re not trying to sweep anything under the rug,” he said.
In a statement, Johnson & Johnson told Insider that it takes all adverse reactions seriously. The company said it would “carefully assess the events” and share any findings with the FDA.
“There is no greater priority than the safety and well-being of the people we serve,” the statement said.
The link between J&J’s shot and blood clots remains tenuous
Just four blood-clot cases have been identified among people who’ve gotten Johnson & Johnson’s shot so far. In one of those cases, a participant in the company’s clinical trial died of a clotting disorder.
The other three blood-clot cases occurred during J&J’s US rollout, which has administered nearly 5.4 million doses of its vaccine. That’s fewer than one clot case per 1 million shots.
Experts aren’t convinced there’s a cause-and-effect relationship at all, though.
“It isn’t really clear how many people get blood clots anyway,” Caplan said. ‘That makes it hard to know whether it’s connected to vaccination.”
The European Union’s health regulator, the European Medicines Agency (EMA), announced its investigation after receiving information about the blood-clot cases from the FDA, Bloomberg reported. The EU authorized Johnson & Johnson’s vaccine in March and is scheduled to roll out the shot later this month.
The agency said it wasn’t sure what relationship, if any, existed between the vaccine and blood clots.
Earlier this week, the EMA announced that potentially fatal blood clots might be a rare side effect of AstraZeneca’s vaccine, which has been authorized in more than 110 countries but not yet in the US. Both that shot and Johnson & Johnson’s are viral-vector vaccines, which introduce a coronavirus gene into the body using a genetically engineered common-cold virus. Scientists don’t know whether the platform itself could be linked to clotting.
Still, any risk of clots should be weighed against the risk of getting COVID-19, Caplan said.
“If I live in Brazil and I’m still seeing 3,000 deaths a day, and somebody said to me, ‘We’re going to pull AstraZeneca vaccine out of here because we found somebody who died of a blood clot that might be related to the vaccine,’ I’d say, ‘You better recalculate your risk-benefit ratio,'” he said.
The bigger problem is a lack of supply
For now, the most pressing issue with Johnson & Johnson’s vaccine isn’t any safety concern – it’s the lack of consistent supply.
Johnson & Johnson promised to ship 24 million doses in US this month, but it’s unclear if the company will meet that goal, given the recent manufacturing issues, which occurred at a plant run by Emergent Biosolutions, a US government contractor.
Quality-control managers must first test 62 million doses to see if they can be salvaged, and the FDA must also certify that the Maryland plant can release more doses to the public.
Jeff Zients, the White House COVID-19 response coordinator, said at a Friday briefing that Johnson & Johnson “expects a relatively low level of weekly dose delivery” until the FDA signs off on the plant.
The total number of Johnson & Johnson shots allocated to states and other jurisdictions is expected to drop around 85% next week, to around 1.5 million doses. But that decrease follows an unprecedented surge of roughly 11 million doses last week.
Johnson & Johnson has said it’s still on track to provide close to 100 million doses by the end of May.
Countries are beginning to explore an usual way of using coronavirus vaccines, in order to avoid giving some groups a second dose of the AstraZeneca shot: mixing and matching with another type of vaccine.
Germany and France have both recommended that some groups take a different second dose, citing a link between the AstraZeneca shot and very rare blood clots. Canada and Norway are considering doing the same.
Germany recommended on April 1 that those under 55 receive an mRNA vaccine alternatives, such as the Pfizer and Moderna vaccines, as a follow up shot. France recommended the same on Friday for people under the age of 60.
The European Medicines Agency (EMA) announced on Wednesday that unusual blood clots with low platelets should be listed as a “very rare side effect” of the AstraZeneca vaccine.
The EMA says that the benefits of the vaccine outweigh its risks, and experts say that a definite link between the shot and the blood clots has not been established.
Canadian health authorities are examining the evidence for dose mixing, Dr. Howard Njoo, Canada’s deputy chief public health officer, said on Thursday.
Although it is not widely recommended yet for COVID-19 vaccines, mixing doses from different manufacturers is not unusual, one expert said.
“Mixing different manufacturers vaccines is called ‘heterologous prime boost’ and is something that has been looked into long before COVID,” Prof. Paul Hunter, professor of medicine at the University of East Anglia, told Insider in an email.
It “often appears to give better protection,” although it is not known whether this holds true in the case of COVID-19, Hunter said.
“Personally, I would not worry too much”, he said, but “before recommending this on a wider scale I would prefer to await the results” of trials like the one Norway is watching.
The UK is not recommending dose-mixing, and says that people who have taken one shot of AstraZeneca’s vaccine should go ahead and get the second.
Health experts told Insider that in spite of the unusual blood clots being listed as a very rare side effect of the vaccine, getting the shot is still safer than flying in a plane.
The interview with Dr Astles was published hours after the European regulator announced that potentially fatal blood clots can be an extremely rare side effect of the AstraZeneca vaccine and cerebral blood clots, and UK officials withdrew its use in under-30s.
Astles, a pharmacist and subject leader at the University of Huddersfield, said her brother had been “extraordinarily unlucky,” and urged people to continue taking the shot if offered it.
“We trust the process, we trust the regulator, and despite what has happened to our family we don’t want people to be scared off. That’s the message we want to get across,” she said.
Astles said her brother, a local government lawyer in northwest England, had generally been fit and healthy.
Mr. Astles went to the emergency room after is symptoms got “a great deal worse.” After 10 days of worsening symptoms, Mr. Astles died on April 4, almost three weeks after receiving the vaccine, the Telegraph reported.
“There was a strong suspicion right from the very beginning that it was the Astra vaccine because of his very low platelet levels,” she said.
She said that “emotionally,” the family were furious at losing her brother, but intellectually, “there’s nothing in our minds to be really furious about. My brother was just extraordinarily unlucky.”
“Despite what has happened to our family, we strongly believe that everyone should go for their first and second doses of the AstraZeneca vaccine,” Astles told the Telegraph.
“If we all have the vaccine, a few of us might have a blood clot but the evidence is that fewer people will die.”
The Telegraph reported that Astles’ death is too recent for the coroner – an official who investigates unusual deaths – to have produced a formal cause of death for him.
Dr. Astles said that her brother’s diagnosis was a “cerebral sinus thrombosis and subarachnoid hemorrhage” with “low platelets and extraordinarily high d-dimer.”
Low platelets alongside the cerebral blood clots is one of the unusual side effect of the AstraZeneca vaccine, the European Medicines Agency said on Wednesday.
If the clot is caught early, the symptoms can often be treated with anti-clotting medication.
The UK has advised that people under the age of 30 be given an alternative to the AstraZeneca vaccine, as the risk-to-benefit tradeoff is “more finely balanced” in younger people, the Joint Committee on Vaccines and Immunisation said on Wednesday.