Pause remains on J&J vaccine

A temporary pause on the rollout of Johnson & Johnson’s COVID-19 vaccine in the US will likely remain in place for a week or more while scientists and vaccine regulators watch for more cases of rare but dangerous blood clots that a small number of J&J vaccine recipients developed.

More than 6.8 million people had received the J&J vaccine in the US between its emergency use authorization on Feb. 27 and the pause recommended by US Food and Drug Administration and the Centers for Disease Control and Prevention on April 13. During that time, the FDA and CDC received reports of six women that developed cerebral venous sinus thrombosis (CVST), a dangerous blood clot in the brain, and thrombocytopenia, the condition of low platelet levels.

The pause came a week after European regulators determined that AstraZeneca’s COVID-19 shot was linked to rare and occasionally lethal cases of CVST with thrombocytopenia. The AstraZeneca and J&J shots are both adenoviral vector vaccines. The similar and unusual combination of clots and low platelet counts seen in recipients of both vaccines prompted CDC and FDA officials to pause further use of the J&J shot. J&J voluntarily paused rollout of the vaccine in Europe too.

On April 14, the CDC’s Advisory Committee on Immunization Practices (ACIP), a team of independent scientists that makes recommendations for how vaccines should be used, convened for an emergency meeting to discuss the J&J vaccine.

During the meeting, CDC scientist Tom Shimabukuro said that the CDC and the FDA became aware of the cases of CVST and thrombocytopenia through the Vaccine Adverse Event Reporting System, which allows health-care workers, patients, and caregivers to report side effects from vaccines. The system “performed exactly as intended in this case,” he said.

CVST is a serious and rare condition, and the six cases reported in people who got the J&J vaccine are about 4 to 15 times the expected rate, Shimabukuro said. But even that rough prediction may be an underestimate, he added, since it doesn’t account for the unusual combination of CVST with low platelet levels. He described the pairing as a “paradox” because platelets usually facilitate blood clotting.

The committee discussed another puzzling development: five of the six women tested positive for antibodies against a clotting protein called platelet factor 4 (PF4). Several people who developed clotting and thrombocytopenia after receiving the AstraZeneca vaccine also had PF4 antibodies. Researchers are still trying to understand the genesis of those antibodies and their role in these serious side effects. Some scientists speculate that the problem may lie in the adenoviral vector vaccine technology employed by both AstraZeneca and J&J, although it is unclear how adenoviral vectors would trigger PF4 antibodies to develop or why the cases are so rare.

At the time of the ACIP meeting, one of the six women who developed rare blood clots after getting the J&J vaccine had died, three remained hospitalized, and two were recovering at home. Symptoms of clotting developed about 6 to 13 days after vaccination. Because of that timing, Sara Oliver of the CDC’s Epidemic Intelligence Service estimated that any cases of clotting and thrombocytopenia have likely already occurred in people vaccinated before March 30. But more incidents could arise in people vaccinated since March 30, and the CDC will be watching for new reports.

For that reason, ACIP committee members decided to delay making new decisions on the J&J vaccine. The pause will likely remain in place for at least a week until the committee reconvenes to assess any new data. The pause will provide time for health-care workers to learn about the potential risks of the J&J shot and monitor vaccine recipients for symptoms.

If the agencies decide that the clots are caused by the vaccine, they will face the difficult decision of balancing the rare risks posed by the shot with the abundant risks posed by COVID-19. When the CDC and the FDA announced the pause, the 7-day average of COVID-19-related deaths in the US was still more than 700 per day. The agencies will have to choose between leaving the vaccine on the market, limiting its use to certain demographics, or pulling it completely.

More than 180 million doses of the messenger RNA vaccines from Pfizer and Moderna have been administered in the US so far, with no reports of individuals developing both CVST and thrombocytopenia after those vaccinations.