C.D.C. Panel Keeps Pause on Use of J&J Vaccine, Weighing Risks

An advisory committee debated the very few cases of a rare blood disorder and worried about the suspension’s effect on global needs for a one-shot, easy-to-ship vaccine.,


Continue reading the main story

Supported by

Continue reading the main story

The pause in the use of Johnson & Johnson’s Covid-19 vaccine may continue for a week to 10 days, after expert advisers to the Centers for Disease Control and Prevention determined on Wednesday that they needed more time to assess a possible link to a rare but serious blood-clotting disorder.

The decision not to reinstate the vaccine has painful consequences, nationally and globally. It may further erode public confidence in vaccination in general and slow the rollout of desperately needed shots to rural and underserved areas and homebound people. The vaccine is considered ideal for hard-to-reach people and places because it requires only one shot and is more easily stored and shipped than the vaccines made by Moderna and Pfizer-BioNTech, which must be kept at very low temperatures.

“Putting this vaccine on pause, for those of us that are frontline health care workers, has really been devastating,” Dr. Camille Kotton of Harvard Medical School told the panel. She said that losing the Johnson & Johnson vaccine even temporarily represented a big blow to efforts to stop the pandemic, especially in underserved communities.

The pause, first recommended on Tuesday by U.S. health officials, led Johnson & Johnson to delay its rollout of the vaccine in Europe, where several countries were poised to start administering it this week. The continent is reeling from the fallout over rare cases, sometimes fatal, of a similar blood disorder that has prompted several nations to limit or reject the widespread use of the AstraZeneca-Oxford vaccine and recommend alternatives.

South Africa, devastated by a worrisome variant of the virus that emerged there, also suspended use of the Johnson & Johnson vaccine. Australia announced it would not purchase any doses. And the European Union indicated that it would consider new deals only with companies that were not using the technology employed by the Johnson & Johnson or AstraZeneca vaccines.

Noting that many countries follow the United States’ lead when it comes to vaccines, Dr. Grace Lee of Stanford University, an expert on the panel, said that although the committee’s responsibility was to the United States, “I also feel the weight of the burden of a global responsibility that we also have and the impact that our decision-making can potentially worsen inequities.”

The advisory group’s emergency meeting on Wednesday was called to review the reason for the pause: six cases of rare and severe blood clots in the brain in women ages 18 to 48, one of whom died. All of the women had received the Johnson & Johnson vaccine before developing the clots, although it is unclear whether the vaccine was responsible. In addition, the panel learned of a seventh woman and a man who experienced the rare condition after receiving the vaccine during its clinical trials.

As of Tuesday, more than seven million people in the United States had received the Johnson & Johnson shot, representing about 5 percent of vaccinations nationwide.

Advisory meetings usually end with a vote on whether or how to use a vaccine. But in this case, the panel members declined to vote after reviewing several options — including whether to limit use of the vaccine to older adults, as many European nations have done — saying that they did not have enough information to assess the potential risks.

Doran Fink, an official of the Food and Drug Administration, proposed a different strategy to the panel, suggesting that the vaccine could go back into use while researchers continued to study the potential risk. Doctors and patients could be provided with information about the findings so that patients could consider whether to accept the vaccine. “Our current thinking is that this risk could be managed by inclusion of warning statements,” Dr. Fink said.

But some experts on the C.D.C. panel leaned in other directions, fearing that more patients could be harmed if vaccinations resumed without a full understanding of the potential risks. One warned that the rare condition could cause long-lasting neurological damage. Others reminded their colleagues of the risk from Covid itself, and the message the panel would send if it prolonged a suspension in the use of a one-and-done vaccine.

The Advisory Committee on Immunization Practices, or ACIP, is a panel of independent experts who advise the C.D.C. on its vaccine policies.

The clotting disorder of concern in the vaccine recipients is different — and much rarer — from typical blood clots, which develop in hundreds of thousands of people every year. The seven women experienced not only clotting in the brain but a notably low level of platelets, parts of the blood that help form normal clots in response to an injury.

None of the women had recently given birth, which can increase the risk of more common blood clots, and only one was known to be taking hormonal treatment. So far, there is no evidence that birth control pills, which can also raise the risk of blood clots, were involved.

Three of the women had large, dangerous clots in other parts of their body, not just in the brain.

The rare combination of severe clots and low platelets stood out to experts as a safety signal. Why it develops is not known, and so far there is no way to predict whether an individual is susceptible.

The condition is very similar to one linked to the AstraZeneca Covid vaccine, also affecting some relatively young women in Europe, where that vaccine was in wide use. Researchers in Germany and Norway found that patients there had developed antibodies that activated their platelets — an aberrant response to the vaccine — setting off a cascade of clotting and bleeding. Specialized blood tests can detect the antibodies to confirm the diagnosis, and some of the U.S. patients tested positive. Not all were tested.

Both AstraZeneca and Johnson & Johnson use adenoviruses to ferry DNA into human cells to create immunity against the coronavirus. Researchers suspect that some aspect of that technology plays a role in the blood disorder. But they also emphasize that because the condition is so very rare, some quirk of biology very likely predisposes certain people to have a bad reaction to the vaccine. If the vaccine alone were responsible, there would be many more cases, some researchers say.

The vaccines made by Moderna and Pfizer-BioNTech employ genetic material called mRNA and do not use viruses.

Much of the world had been counting on the AstraZeneca vaccine to fight the pandemic, but many countries have now restricted its use to adults older than 30 or 50, and some have stopped using it altogether. Some people who are still eligible for it are declining it out of fear. AstraZeneca’s vaccine has not been authorized in the United States, although the company is expected to apply for permission to distribute it here.

Use of the Johnson & Johnson vaccine in the United States began on March 2, and the first case of blood clots in the brain was reported on March 19. About 1.4 million women ages 20 to 50 — the age range of those who had the clots — have received the vaccine.

The panel of experts discussed the known background rates of low platelets and of the clots in the brain — known as central venous sinus thrombosis — in the general population and in younger women like those who had the clots, but noted that there was not enough data to precisely estimate how often the two conditions occurred at the same time.

But based on rough estimates, the clotting disorder in women ages 20 to 50 who received the Johnson & Johnson vaccine occurred at least three times more often than would be expected, according to Dr. Tom Shimabukuro, a safety expert from the C.D.C.

In the coming weeks, he said, the rate would become clearer as more reports arrived. “We’ll get a better picture of what’s going on.”

“Right now, we believe these events to be extremely rare, but we are also not yet certain we have heard about all possible cases, as this syndrome may not be easily recognized as one associated with the vaccine,” Dr. Rochelle P. Walensky, the C.D.C. director, said at a White House news conference on the pandemic on Wednesday.

During the panel discussion, experts noted that the “risk window” for the condition among vaccine recipients was still open and that new cases might emerge, because nearly 3.8 million people had received the shot within the last two weeks. In the six women, the severe clotting developed within about two weeks of the shot.

Other experts encouraged dissemination of health information on diagnosis and treatment of the condition so that awareness would spread among doctors, emergency rooms and people who had received the vaccine. A key point is that the blood-thinner heparin, a common treatment for clots, can harm these patients and should not be used.

Officials also noted that people with the condition needed to be treated as soon as possible because the clots were so serious. Some patients needed invasive procedures to remove large clots from blood vessels in their brains.

Several panel members reiterated that two other vaccines — from Moderna and Pfizer-BioNTech — are available, neither associated with the clotting problem, so continuing the pause would not stop most people in the United States from being vaccinated.

At the news conference, Jeffrey D. Zients, the White House’s pandemic coordinator, said that the pause would not generally interrupt the momentum of the country’s vaccination campaign.

“In the very short term, we do expect some impact on daily averages as sites and appointments transition from Johnson & Johnson to Moderna and Pfizer vaccines,” he said. “We have more than enough Pfizer and Moderna vaccine supply to continue or even accelerate the current pace of vaccinations.”

Public health experts have repeatedly emphasized that the clotting disorder is rare and that the benefits of the AstraZeneca and Johnson & Johnson vaccines far outweigh their risks. But when an adverse effect has the potential to be devastating or fatal — like blood clots in the brain — some regulators and segments of the public consider the risk unacceptable, even if it is extremely rare.

The safety bar for vaccines is set high because they are given to healthy people. The seemingly greater vulnerability of younger people to the clotting disorder is of particular concern, because their risk of severe illness from Covid itself is lower than that in older people. Those differences suggest that over all, compared to older people, younger people may have less to gain and more to lose from the Johnson & Johnson and AstraZeneca vaccines.

Reporting was contributed by Noah Weiland, Madeleine Ngo and Virginia Hughes.

Leave a Reply