On Tuesday, U.S. health authorities urged states and healthcare providers to pause use of Johnson & Johnson's coronavirus vaccine, citing reports of a rare but serious side effect.
According to the Food and Drug Administration and the Centers for Disease Control and Prevention, six women in the U.S. have experienced an unusual combination of blood clots near the brain along with low levels of platelets, the sticky cells that help blood coagulate, after getting vaccinated with J&J's shot.
The events are very uncommon; nearly 7 million people have received J&J's vaccine in the U.S. through April 12. But they bear close resemblance to a side effect linked by European regulators to a vaccine developed by AstraZeneca that uses similar technology as J&J's.
Regulators aim to quickly complete their investigation and update the public within the next few days, likely some time after a CDC committee meets on Wednesday. In the meantime, here's a look at the decision's effects and what could come next.
Will the pause impact vaccine supply?
Unlike some countries that are relying heavily on one vaccine, the U.S. hedged its bets by signing supply contracts with multiple developers. So announcement of the pause Tuesday was accompanied by reassuring messaging from the Biden administration that the decision won't disrupt plans to have enough doses for every American by the end of May.
Jeff Zients, the White House's COVID-19 response coordinator, said the nearly 7 million J&J shots administered to date constituted just 5% of the U.S.'s total. The government has agreements with Pfizer and Moderna for a supply of 600 million vaccine doses, said Zients, who noted he doesn't expect much slowing in the immunization efforts underway.
"We have more than enough supply of Pfizer and Moderna vaccines to continue the current pace of about 3 million shots per day," he said at a Tuesday press conference at the White House. "We're now working with our state and federal partners to get anyone scheduled for a J&J vaccine quickly rescheduled for a Pfizer or Moderna vaccine."
Even in rural and underserved communities where J&J's single-shot regimen and less demanding storage requirements are considered an advantage, Zients said switching vaccines won't limit supply.
"We have plenty of vehicles for delivering that supply, whether it's through the pharmacy channel, whether it's mobile units or community health centers, and all of those are equipped to deliver the Moderna and Pfizer vaccines," he said.
Supply of J&J's vaccine in the coming weeks was already expected to be lumpy following manufacturing errors at a contractor's Baltimore plant that makes the shots. The company has a contract to deliver 100 million doses to the U.S. by the end of June.
What steps could regulators take next?
Recent responses by U.K. and European regulators to similarly rare clotting events among people who received AstraZeneca's vaccine could be a guide for what's to come for J&J in the U.S.
The U.K.'s Medicines and Healthcare Products Regulatory Agency and the European Medicines Agency each began investigations after dozens of cases of abnormal clots alongside low platelet counts were identified across multiple European nations. Many countries temporarily halted immunizations with AstraZeneca's shot while the reviews were underway, and several kept vaccinations paused for longer. Both drug reviewers were under enormous pressure, with coronavirus infections rising across Europe and AstraZeneca's vaccine the most widely available option.
Last week, both announced their findings. The EMA emphasized that the benefits of vaccination far outweigh the risks, but updated the shot's labeling information to warn of the risk of clotting events and called for AstraZeneca to conduct further study.
The MHRA also supported the shot, but a U.K. advisory committee recommended other vaccines be used for adults under 30 years old without underlying health conditions. Regulators in other European countries have recommended age restrictions in place as well.
The FDA now faces a similar choice. Only six events have been identified from roughly 7 million J&J vaccinations in the U.S., compared to about 220 among the 34 million people immunized with AstraZeneca's shot as of last week.
But given the similarities between the particular side effects and the two vaccines, it wouldn't be a surprise to see the CDC's expert vaccine advisory committee recommend a warning or some type of restriction on J&J's shot for any future use. Analysts at SVB Leerink, for instance, predict the committee will recommend some sort of "demographic-based restriction," such as advising against the shot's use in women under 50.
"I still think this could come back with some additional perhaps restrictions on its target population in the interim while they continue to investigate this," said former FDA Commissioner Scott Gottlieb, who is now on Pfizer's board of directors, in an interview on CNBC Tuesday. "That's what we've seen other countries do with the AstraZeneca vaccine."
Could this increase vaccine hesitancy?
More than 122 million people in the U.S., or about 37% of the country's population, have received at least one dose of a coronavirus vaccine. Increasing availability of doses, coupled with states broadening eligibility, has put President Joe Biden's goal of 200 million shots before April 30 easily in reach.
But as supply has improved, there remain concerns that waning demand for vaccinations could make population immunity harder to achieve. Tuesday's news of the FDA and CDC's recommendations to pause use of J&J's shot while the blood clotting cases are investigated further reignited debate over vaccine hesitancy.
In statements and briefings, health and White House officials made clear they hope the move will increase confidence, rather than diminish it.
"The FDA, acting the way they did today, shows that they are indeed the gold standard," said the White House's Zients on Tuesday. "I think that should reassure the American public that they will be very diligent and conservative in how they approach the vaccine."
But reports of any potential serious side effect, however uncommon, could still change public perception of a vaccine viewed as an important tool in the pandemic response.
"Even if there isn't a causal relationship, even if this is exceedingly rare, I think we're going to see that whole conversation get ignited on social media," said Gottlieb, on CNBC.
Another concern is that the FDA and CDC, in reacting assertively to a handful of cases among millions, may unnecessarily fuel doubts about a potential side effect.
Still, a number of public health figures emphasized the potential consequences of a more muted response. "The FDA is cautious because it's important to be responsive to any safety concern," wrote Natalie Dean, an assistant professor of biostatistics at the University of Florida who specializes in vaccine study design, on Twitter. "Long-term trust is easily lost."
The decision to recommend a pause in vaccinations was also aimed at healthcare providers, given the potential to mistreat the rare combination of blood clots and low platelets that's been observed.
"We included the pause in addition to the alert so there was time for the healthcare community to learn what they needed to learn about how to diagnose, treat and report," said Anne Schuchat, principal deputy director of the CDC, in a briefing.