FDA recommends pause of J&J’s COVID-19 vaccine

The US Food and Drug Administration is recommending that healthcare providers temporarily pause administration of Johnson & Johnson’s COVID-19 vaccine after reports of rare blood clots and low platelet counts in six women who received the shot. One woman has died, and another is in critical condition, according to the FDA. The Centers for Disease Control and Prevention is holding a meeting of vaccine experts on April 14 to investigate the cases and make recommendations about how to proceed.

In an April 13 press briefing, CDC and FDA officials emphasized that they don’t know if the cases were caused by the vaccine. The pause comes “out of an abundance of caution,” said acting FDA commissioner Janet Woodcock. More than 6.8 million people have received the J&J shot in the US without major complications.

When millions of people get a vaccine, some are likely to develop blood clots for reasons wholly unrelated to vaccination. But the combination of the specific type of blood clot, cerebral venous sinus thrombosis (CVST), with low platelet levels, or thrombocytopenia, is unusual, since platelets are how most blood clots are made.

“Those two things can occur,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research. “It is their occurrence together that makes a pattern, and that pattern is very, very similar to what was seen in Europe with another vaccine.”

That other vaccine is AstraZeneca’s COVID-19 shot. Last week the European Medicines Agency ruled that unusual blood clots, including CVST, in combination with thrombocytopenia are “very rare” side effects of the AstraZeneca vaccine. Most cases occurred in women under 60.

At the time, European regulators had reviewed 86 cases, including 18 deaths, reported from about 25 million people who got the vaccine. The reports led some countries to limit use of the vaccine to older individuals, who appear to be at lower risk for the rare blood clots. Other countries halted use of the vaccine altogether.

The six cases of CVST and thrombocytopenia linked to the J&J vaccine in the US were in women aged 18 to 48, and symptoms arose 6 to 13 days after vaccination. The CDC and FDA did not provide additional information about these people. With so few cases, it may be hard for the agencies to definitely determine if the vaccine is safe for certain groups of people and risky for others. “The numbers are quite small—small enough that it is hard to generalize, but large enough that we wanted to take action with the pause,” said Anne Schuchat, principal deputy director at the CDC.

One lingering question is why the vaccines would cause blood clots at all. The exact cause is unclear, but there may be a “similar mechanism” behind the issues with the J&J and AstraZeneca shots, which are both adenoviral vector vaccines, Marks said.

The vaccines use genetically engineered adenoviruses, called adenoviral vectors, to deliver a gene for the coronavirus spike protein into human cells. The goal is to trick our cells into making spike proteins, so our immune systems can learn to develop antibodies to the spike and prevent future infections of the coronavirus, which causes COVID-19. AstraZeneca’s adenoviral vector is made from a virus that normally infects chimpanzees; J&J’s vector is made from a virus that infects humans.

FDA officials speculated that rare, unwanted immune responses triggered by the vaccines—perhaps directed at one’s own blood-clotting system—may trigger CVST and thrombocytopenia in a small number of people injected with adenoviral vector vaccines. Marks hesitated to say that the issue was an inherent feature of adenoviral vector vaccines. But he did note that there have been no reports of CVST combined with thrombocytopenia with messenger RNA vaccines from Pfizer and Moderna, even though more than 180 million doses have been administered in the US so far.

CVST itself is rare, with about 2 to 14 cases per million people each year, according to Marks. Immune thrombocytopenia, in which a person’s immune system attacks their platelets, is diagnosed in about 33 people per million each year, according to the National Organization for Rare Disorders. So far, the combination of CVST and thrombocytopenia has occurred in only about one in a million people who received J&J’s vaccine, but as Marks emphasized, it is the combination of those two issues that the FDA deems unusual.

Pausing the vaccine rollout will provide time for health care workers to become vigilant for unusual blood clots and thrombocytopenia in people who recently received the J&J vaccine. Standard treatments for blood clots, such as the anticoagulant drug heparin, “could cause tremendous harm” or even death in the context of CVST and thrombocytopenia, Marks said. Such cases will require different treatments.

It is unknown how long the FDA’s recommended pause will last or if it will significantly delay US president Joe Biden’s goal of making vaccines available to all US adults by May.

“The timeframe will depend on what we learn in the next few days,” Woodcock said. The CDC’s Advisory Committee on Immunization Practices (ACIP) will discuss the available evidence of the issue during its April 14 meeting. In the meantime, J&J says it will voluntarily delay the rollout of its vaccine in Europe.