“I’d like to stress these events appear to be extremely rare. However, covid-19 vaccine safety is a top priority for the federal government, and we take all reports of adverse events following vaccination very seriously,” said Janet Woodcock, acting commissioner of the Food and Drug Administration, who said the investigation would move forward rapidly and could conclude in days.
The recommendation resulted in swift action, with the U.S. military and many states announcing they were suspending the use of the single-shot Johnson & Johnson vaccine. More than 7.1 million doses of Johnson & Johnson’s vaccine had been administered throughout the United States as of Tuesday. About 16 million doses have been delivered to states and territories, and through federal channels, since the beginning of March.
The one-shot option has proved popular for people who gravitated to its convenience, and states have deployed it in a variety of settings, from mass vaccination sites to targeted efforts to reach transient populations, such as the homeless. The decision to pause the use of the vaccine in the United States ignited a debate on social media, with some arguing that the risk of covid-19, the disease the virus causes, remained higher than the rare risk of an adverse effect from vaccination.
“I think it’s the prudent thing to do. I think it’s real — this is a rare, but real association,” said Paul A. Offit, a vaccine specialist at Children’s Hospital of Philadelphia. “They want to determine if this is the tip of a bigger iceberg.”
Mark A. Crowther, chair of the Department of Medicine at McMaster University in Canada, said the pause should be used to quickly assess the risk and determine if there are people for whom the risk outweighs the benefit of the vaccine.
But he worried that the attention might fuel vaccine hesitancy, even though the risk of developing a clot after receiving the vaccine appears far lower than the chance of a clotting issue caused by a severe covid-19 infection or from using hormonal birth control, such as oral contraceptives.
“Having the FDA or CDC make a decision to very transiently pause the use of this vaccine makes good sense while they investigate it,” Crowther said.
Woodcock and other federal health officials stressed that one reason to pause the use of the vaccine — which is the United States’ third authorized coronavirus shot — was to make sure medical professionals were aware that blood clots potentially associated with a vaccine should not be treated with a conventional drug, heparin, which could exacerbate the clots.
All six cases of the rare brain clots in the United States involving the Johnson & Johnson vaccine occurred among women between the ages of 18 and 48, and symptoms developed six to 13 days after vaccination, according to a statement issued by the FDA and the Centers for Disease Control and Prevention. One vaccine recipient, a Virginia woman, died in March, and her death is being investigated by the CDC, Virginia state officials said in a statement Tuesday. Another woman is in critical condition, an FDA official said Tuesday.
The person in critical condition was treated with heparin, according to a person familiar with the situation who spoke on the condition of anonymity. A CDC official said two of the six patients have been discharged and three remain in the hospital.
Roughly 1 million women in that age group have received the vaccine, according to officials.
With so few cases, regulators and clinicians still face many unknowns about whether there are risk factors that make people susceptible to the reactions.
Peter Marks, a top vaccine official at the FDA, noted that the normal rate of brain blood clots in the general population was 2 to 14 per million people a year. It has long been recognized that hormonal birth control can increase the risk of clots in women, but Marks said there was no clear evidence showing that women on the pill who received the vaccine were more likely to develop clots.
The clots are atypical, a rare phenomenon in which two seemingly conflicting problems are present: Blood clots are forming at the same time that platelets, blood cells involved in clotting, are plunging.
That combination is not something that would typically occur in healthy young people, according to Gowthami Arepally, associate professor of pathology at Duke University School of Medicine.
Marks said the clots are extremely similar to an unusual set of symptoms detected among people who received the vaccine developed by AstraZeneca and the University of Oxford: blood clots paired with low levels of platelets. European regulators and scientists have determined that syndrome is possibly triggered by an immune reaction to that vaccine, which uses a similar technology to the Johnson & Johnson shot to protect against covid-19.
One leading theory is that a component of the vaccine — it isn’t certain which one — triggers the immune reaction. Investigations of the cases that emerged after use of the AstraZeneca and Oxford vaccine showed that people developed antibodies that bind to platelets, causing them to be activated and cleared, while also promoting clotting. A similar rare reaction has been documented to the drug heparin.
“There are two dual competing concerns I have with these reports: One, obviously, is the actual fatalities and complication rates being described in healthy individuals getting the vaccine. The competing concern I have is it [will] add to the anti-vaxxer sentiments that vaccines are not safe,” said Arepally, who is working as a consultant to AstraZeneca to help the company review the cases and the science around the clotting events.
“The overwhelming majority [of people vaccinated] are benefiting, but obviously we really need to identify the causes and the reasons why these rare complications are occurring,” Arepally said.
Health officials said people who have received the Johnson & Johnson vaccine who develop a severe headache, abdominal pain, leg pain or shortness of breath within three weeks after vaccination should contact their doctor. They should not be treated with heparin, the commonly used blood thinner that could exacerbate the clotting.
The decision to pause vaccination requires regulators to assess the risks of a rare side effect and the risk of covid-19. The CDC will hold a meeting Wednesday of its Advisory Committee on Immunization Practices to review the cases and assess their potential significance, its statement said. The FDA will continue to investigate the cases.
“Until that process is complete, we are recommending a pause in the use of this vaccine out of an abundance of caution,” the statement said. “This is important, in part, to ensure that the health care provider community is aware of the potential for these adverse events and can plan for proper recognition and management due to the unique treatment required with this type of blood clot.”
Regulators in the United Kingdom, for example, found that the risks of covid-19 were greater than the risks posed by the AstraZeneca-Oxford vaccine to all age groups except for adults under age 30 and said those younger adults should be offered other vaccines. Various countries have imposed restrictions on the vaccine, reserving it for older people.
The type of clot, called cerebral venous sinus thrombosis, was seen in combination with low levels of blood platelets, the agencies said. Treatment is different from what might typically be administered; while the anticoagulant heparin is often used to treat blood clots, it may be dangerous to give that drug in this situation. Alternative treatments need to be given, they said.
“There are highly effective treatments; it’s just average clinicians will never have seen a case of this,” Crowther said.
The blood clots, paired with low levels of platelets, were first detected in people in Europe who had received the vaccine developed by AstraZeneca and the University of Oxford. European regulators in their investigation of the AstraZeneca vaccine said that out of 34 million people vaccinated, 222 cases of clots had been reported. There were at least 18 deaths.
The clots have not been associated with the Moderna and Pfizer-BioNTech vaccines, which rely on a different technology, and those vaccinations are continuing.
In a statement, Johnson & Johnson spokesman Jake Sargent said the company shares all adverse event reports with health authorities.
“At present, no clear causal relationship has been established between these rare events and the [Johnson & Johnson] COVID-19 vaccine,” Sargent said. “We continue to work closely with experts and regulators to assess the data and support the open communication of this information to healthcare professionals and the public.”
White House covid-19 coordinator Jeff Zients said the call for a pause in the rollout of the vaccine was taken out of “an abundance of caution.”
“This announcement will not have a significant impact on our vaccination plan: Johnson & Johnson vaccine makes up less than 5 percent of the recorded shots in arms in the United States to date,” Zients said.
One of the cases happened in a Nebraska woman in her late 40s who experienced a blood clot two weeks after receiving the Johnson & Johnson vaccine and received treatment at the Nebraska Medical Center in Omaha, according to state and federal health officials. The woman remained hospitalized, state officials said Monday.
Johnson & Johnson has committed to delivering nearly 100 million doses of its vaccine for distribution in the United States before the end of May and has said it can produce 1 billion doses globally by the end of the year. Its vaccine has been seen as a key component of the nation’s drive toward providing enough shots for all adults, especially because it requires only one shot.
The United States has banked on an increasing supply of the Johnson & Johnson vaccine throughout 2021. The Biden administration brokered a deal with Merck to produce raw vaccine substance for Johnson & Johnson beginning in the second half of the year, and to help with finishing the vaccine and filling it into vials as soon as next month.
The government and the companies have not disclosed how many doses would be available under that agreement, but it would set up a major production pipeline for the United States and potentially exports to other countries. It is unclear how the U.S. pause will affect uptake of the vaccine in the rest of the world, but South Africa announced Tuesday that it would suspend use of the shot.
Globally, Johnson & Johnson has agreed to sell 500 million doses to developing nations via the Covax purchasing agreement, which is affiliated with the World Health Organization and is dedicated to steering vaccines to disadvantaged countries. Johnson & Johnson has agreed to sell up to 400 million more doses to a group purchasing organization for African countries.
CVS and Walgreens announced they would pause using the Johnson & Johnson vaccine, and many states advised providers to stop administering the vaccine until the CDC advisory committee meets. State officials said they were not given any heads-up about the recommendation to pause.
“We were not informed prior to the announcement,” said Michael Fraser, executive director of the Association of State and Territorial Health Officials. “We are assessing the impact in the states. We’re supportive of an abundance of caution, but we also need to balance getting everyone vaccinated as soon as possible.”
Pentagon press secretary John Kirby said in a statement that the Defense Department is “immediately pausing” use of the Johnson & Johnson vaccine at the recommendation of the FDA and CDC.
“We are communicating this pause to our military health facilities and are reviewing our global vaccine distribution to address this issue and ensure we can continue to provide vaccines to our DoD population at home and abroad,” Kirby said. “At this time, we do not know how long the pause will last. We will continue to communicate to the force as we learn more.”
The decision is a blow especially for the military because the Johnson & Johnson vaccine does not require the cold storage that others do to reach far-flung locations. Lt. Gen. Ronald Place, director of the Defense Health Agency, said in a news conference at the Pentagon last week that defense officials had “targeted the overseas community” for the Johnson & Johnson vaccine and had to adjust after the recent spoilage of millions of doses.
Despite a recent dip in shipments of Johnson & Johnson’s vaccine, clinics were scheduled to use the shot throughout the country, from a Walmart drive-through in Bentonville, Ark., to a clinic at Canisius College in Buffalo.
Sites in a handful of states temporarily halted the use of Johnson & Johnson’s vaccine last week after adverse reactions were reported, though these were immediate events consistent with common side effects, such as dizziness. The adverse reactions were reported in Colorado, Georgia, Iowa and North Carolina. The CDC said it investigated and found no reason for concern.
The emergence of the rare blood clots fueled concerns that confidence in coronavirus vaccines could be shaken — with potentially serious consequences.
“It is good to be transparent about safety profiles of each of the vaccines, but also very important to put that safety profile in appropriate context. For most populations in most countries, the benefits of both of these vaccines significantly outweigh the risks,” said Krishna Udayakumar, a professor of medicine and director of the Duke Global Health Innovation Center. “If the risk of rare adverse events leads to significant increase in vaccine hesitancy, we will have a much harder task to vaccinate the world.”
Dan Lamothe and Isaac Stanley-Becker contributed to this report.