J&J’s vaccine was highly effective at preventing COVID-19 in trials, but has come under scrutiny across the world following reports of rare unusual blood clots in six women aged 18 to 48 who received the vaccine in the US on April 13. At the time, 6.8 million Americans had received the single dose vaccine.
The European Medicines Agency (EMA) said on April 20 that unusual blood clots with low platelets were a very rare side effect of J&J’s vaccine. But the overall benefit of the vaccine outweighed the very low risk of blood clots, it said. European countries can make their own decisions on vaccine rollouts.
The US immediately resumed its J&J vaccine rollout on April 23 after the Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) said the benefits of the shot outweighed its risks. The ruling followed a 10-day investigation.
The Danish Health Authority said that it would continue to monitor the data coming out of the US.
No Danes have received J&J’s vaccine because it was put on hold by the Danish Health Authority while they evaluated its risks.
The Danish Health Authority said that other vaccines were available, and that the COVID-19 outbreak was under control in the country. Denmark has around 760 reported new cases each day, compared with more than 4,500 daily cases in December 2020, according to Johns Hopkins University.
Banning J&J’s shot means a four-week delay in getting 20 to 39 year olds immunized, the Danish Health Authority said. The country is using COVID-19 vaccines from Pfizer-BioNTech and Moderna instead, which have had no safety concerns so far.
Denmark also stopped using AstraZeneca’s shot on April 15, following similar concerns about the risk of unusual blood clots. AstraZeneca and J&J’s vaccines use a similar technology.
“One should also bear in mind that, going forward, we will first and foremost be vaccinating younger and healthy people,” Helene Probst, deputy director general at the Danish Health Authority, said.
Johnson & Johnson shares pushed to a three-week high Tuesday, with the company restarting shipments of its COVID-19 vaccine to Europe after the European Union’s drug agency said its benefits outweigh the potential risk of a “rare” side effect of blood clots.
The agency said a warning should be added to product information about the Janssen-branded vaccine but also said the overall benefit-risk remains positive.
Shares of Johnson & Johnson rose as much as 3.1% to trade above $167 each, marking their first time above that price since March 29. The shares had added about 11% over the past year.
The drug maker said it will resume shipments of the vaccine in the European Union, Norway and Iceland, and that it will provide updated guidance from the medicines agency and healthcare professionals to national healthcare authorities.
“We appreciate the rigorous review of the [Pharmacovigilance Risk Assessment Committee] and share the goal of raising awareness of the signs and symptoms of this very rare event to ensure the correct diagnosis and appropriate treatment,” said Paul Stoffels, J&J’s chief scientific officer, in a Tuesday statement.
The blood-clot cases occurred in people less than 60 years of age and most were in women. The clotting took place within three weeks of receiving the vaccine.
US federal agencies may need two weeks or more to know whether Johnson & Johnson’s coronavirus vaccine is linked to rare blood clots, two senior White House health officials told Politico on Saturday.
US regulators recommended a pause in the distribution of J&J’s shot last Tuesday due to six reports of clotting among women who’d recently received the vaccine.
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, the condition occurs in about five people out of every million.
The Centers for Disease Control and Prevention’s vaccine advisory panel is scheduled to convene Friday to discuss whether to lift the vaccine pause. But two health officials told Politico that the CDC still might not have enough data by then to determine if J&J’s vaccine indeed causes rare clots.
US regulators may ultimately consider placing age- or gender-based restrictions on the shot, which has been authorized for people ages 18 and older. Alternatively, regulators could simply deliver stronger warnings about possible blood clots in unusual cases.
Many political leaders and medical experts worry that if regulators take too long to evaluate the potential blood clot link, an increasing share of Americans will lose trust in J&J’s vaccine.
“The longer the pause is, the longer it’s going to take for us to convince people that this particular vaccine is safe again,” Arkansas Gov. Asa Hutchinson told Politico.
Peter Gulick, an associate professor of medicine at Michigan State University, said the J&J pause could delay the prospect of herd immunity – the threshold beyond which the virus won’t be able to pass easily from person to person.
“The fear is that, hearing all this, the anti-vaxxers and even the ones on the fence are falling off the fence now into the arena of ‘I don’t think I want to get any vaccine until things are known a little more,'” Gulick told Insider. “We may have taken two steps backwards as far as our wanting to get herd immunity.”
Searching for blood clots in a ‘muddied water’ of data
“It’s important from the perspective of the public: When we say rare, what does that mean?” Dr. Beth Bell, a professor of global health at the University of Washington, said during the meeting. “I want to be able to feel comfortable with my family members and myself getting this vaccine.”
US regulators are now encouraging doctors to report any post-vaccination CVST cases over the last few weeks. Regulators are also working with Johnson & Johnson to find out more about the six reported cases – in particular, whether the women had underlying health problems or were taking any medications that could have predisposed them to clotting.
So far, regulators have noticed a few patterns: The women were between the ages of 18 and 48. They also had a rare combination of CVST and low levels of platelets – colorless blood cells that help clots form.
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.
“This observation of the low platelet count is part of the mystery and something that has to be worked through to see if that’s connected or not,” Namandjé Bumpus, director of the pharmacology and molecular sciences department at Johns Hopkins Medicine, told Insider.
But medical experts stressed the need for more data before associating the clots with any particular group yet.
“Everything is just like a big muddied water and then you just try to clear things out as much as you can to try to evaluate what is going on,” Gulick said.
Vaccinations may slow for the homeless, prisoners, or rural Americans
Shortly after US regulators announced a pause in J&J’s vaccine, White House COVID-19 coordinator Jeff Zients said the recommendation wouldn’t affect the pace of the US vaccine rollout.
“We have more than enough supply of Pfizer and Moderna vaccines to continue the current pace of about 3 million shots per day,” Zients said at a Tuesday press briefing.
Indeed, many health departments, pharmacies, and vaccine clinics that planned on administering Johnson & Johnson were able to quickly procure other shots so people didn’t lose their appointments.
But some vaccination sites – particularly those in rural areas – were forced to shut down temporarily. A state-run mass vaccination site in Aurora, Illinois, was canceled earlier this week, terminating appointments of 1,000 people. Around the same time, a Johnson & Johnson clinic in Jefferson County, Illinois, put vaccinations on hold.
The J&J pause has also slowed the pace of vaccinations for homeless people, prisoners, and those unable to leave their homes due to illness or old age. J&J’s vaccine is the only single-dose shot authorized in the US, so it’s the easiest to administer. It’s also easier to store than the Pfizer or Moderna vaccines (it can be kept in standard refrigerators rather than freezers).
On top of that, people may gravitate toward J&J’s vaccine if they’re afraid of needles or have difficulty taking time off work to get vaccinated.
“We’re actually seeing that some people opt for the Johnson and Johnson shot just because of their circumstances – it’s one dose, it’s available, and so on,” Johan Bester, director of bioethics at the University of Nevada, Las Vegas School of Medicine, told Insider.
Without the J&J option, medical experts said, US health officials may have a harder time convincing more Americans to get vaccinated – even as new, more contagious variants drive up cases across the country.
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.
It’s still unclear if the AstraZeneca vaccine is causing the blood clots, or if it’s just a coincidence.
MHRA maintains the shots are safe. Seven deaths out of more than 18 million AstraZeneca doses delivered by March 24 still means that adverse outcome possibly related to the shot is extremely rare.
“The benefits … in preventing Covid-19 infection and its complications continue to outweigh any risks and the public should continue to get their vaccine when invited to do so,” Dr. June Raine, the chief executive of the MHRA, told the BBC.
Many countries have resumed use of AstraZeneca’s vaccine
Many resumed or partially resumed its use after the European Medicines Agency and the World Health Organization emphasized its safety.
“The benefits of the AstraZeneca vaccine in preventing COVID-19, with its associated risk of hospitalization and death, outweigh the risks of side effects,” the European Medicines Agency said in a press briefing March 31, echoing what the regulator said in the weeks prior.
As Insider’s Dr. Catherine Schuster-Bruce previously reported, the EMA said an expert panel including hematologists, neurologists, and epidemiologists could not identify any specific risk factors including age, gender, or previous medical disorder that raised some people’s risk of “these very rare events.”
While there are some theories as to why a vaccine could lead to blood clots, none have been proven in this case, EMA said.
The European Medicines Agency (EMA) said it found no increased risk of blood clots overall with AstraZeneca’s vaccine. But it couldn’t rule out a link between the vaccine and very rare, serious blood clots in the brain, or a clotting disorder called disseminated intravascular coagulation (DIC), particularly in women under 55 years old.
The EMA still recommended that people in this demographic take the shot because the risk of these blood disorders was “extremely small.”
Despite the recommendation, France announced Friday that it would not give people under 55 AstraZeneca’s vaccine.
Ian Douglas, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, told Insider that the EMA’s announcement was not worrying, but “reassuring.”
It not only showed that potential side effects were being monitored closely, but that regulators were being upfront with the public, he said.
“For these reports to happen, there needs to be a suspicion of a link. But everytime we hear it, it won’t mean that it has been caused by the vaccine necessarily,” he said.
“It would be worse if all this was being done in secret, and something got out.”
Lots we still don’t know about the rare blood clots
There are lots of details that we don’t yet know about the 25 reported cases of serious clots: 18 in the brain, seven elsewhere in the body, related with DIC.
It’s possible that these people were at increased risk of blood clots anyway. For example, they may have had underlying illnesses linked to clots, including COVID-19, or an inherited blood disorder. Smoking, the combined oral contraceptive pill, and hormone replacement therapy are all common reasons a woman under 55 may have an increased blood-clot risk.
The EMA also said that a greater number of women under 55 may have been immunized with AstraZeneca’s vaccine, due to targeted vaccine campaigns in different EU countries.
The EMA has updated the AstraZeneca vaccine’s leaflet for patients and healthcare professionals to include signs and symptoms of clotting, so people know when to seek help. A severe or worsening headache or blurred vision after immunization requires prompt medical attention, for example, whereas a mild headache doesn’t.
Regulators may well establish more potential links between serious illness and other COVID-19 vaccines over the next few months, and issue more guidance. This shouldn’t cause alarm: it’s simply a sign that the monitoring system works.
Several European countries have paused their use of the AstraZeneca COVID-19 vaccine due to a few reports of blood clots in those who got the shot.
However, health experts and officials have said there’s no evidence that the vaccine causes clots. It’s more likely coincidental that some vaccine recipients experienced bleeding abnormalities around the time they received their vaccine.
In fact, AstraZeneca reviewed its vaccination records and found there were fewer events of reported blood clots in the vaccinated population than in the general population.
“No vaccines have been shown to cause blood clots,” Daniel Salmon, director of the Institute for Vaccine Safety at Johns Hopkins University, told Insider. He added that he would not be worried about experiencing them as a vaccine side effect, even if he were a person at high risk of blood clots.
Some of the risk factors for blood clots – serious injury or surgery, confinement to bed, pregnancy, and obesity, according to the National Blood Clot Alliance – overlap with the eligibility criteria for COVID-19 vaccines. In many countries, shots are being given first to bedridden residents of long-term care facilities and people with preexisting conditions.
Some countries have stopped using the vaccine, despite WHO recommendations