In a 10 to 4 vote, a committee of the U.S. Centers for Disease Control (CDC) on April 23 decided to lift the temporary hold on using the COVID-19 vaccine made by Johnson & Johnson/Janssen. The U.S. Food and Drug Administration (FDA) and CDC had temporarily halted vaccination with the J&J shot on April 13 after six reports of unusual blood clots in the brain occurred among nearly 7 million people vaccinated with the shot in the U.S.
Within hours, CDC director Dr. Rochelle Walensky accepted the panel’s recommendation and FDA officials said vaccinations could resume immediately. “The American public should feel reassured by the safety protocols we have in place for COVID-19 vaccines,” said Walensky at a briefing following the committee’s decision.
The panel of 15 independent experts was under some pressure to make a decision about the safety of the vaccine, which is the only single-shot vaccine for COVID-19 currently authorized in the U.S. But after an initial meeting on April 14, the group decided it needed more information.
Over the past week, an additional nine cases of unusual blood clots, called cerebral venous sinus thrombosis (CVST) were reported, bringing the total so far to 15 cases. All 15 have occurred in women, and most were in their 30s. However, since that’s still among several million people who had recently been vaccinated with the shot, CDC vaccine-safety experts still felt the overall risk is very small.
To put those 15 cases in context, Dr. Sara Oliver, from the CDC’s National Center for Immunization and Respiratory Diseases, and her team presented data from models they constructed to estimate how the 11-day pause in using the J&J vaccine affected COVID-19 cases, hospitalizations and death. The models showed that if the vaccine were reinstated for all adults over age 18 years, there would be 26 to 45 additional cases of the rare blood clots side effects over the next six months, but 800 to 3,500 fewer admissions to the ICU and anywhere from 600 to 1,400 fewer deaths. If officials restricted the vaccine only to people over age 50—which might make sense given that younger people are more at risk of the clotting side effect— they would expect two to three additional cases of clotting compared to 300 to 1,000 fewer ICU admissions and 40 to 250 fewer deaths.
Oliver also broke down the data at the individual level, and reported that for every one million doses of the vaccine administered to women aged 18 to 49—the group at highest risk of the clotting side effect—13 cases of clotting might be expected.
J&J representatives at the meeting reiterated that the vaccine starts protecting people against disease within days of administration, and that data from the company’s clinical trials showed it was 85% efficacious in protecting people from severe COVID-19, including against new variants of the virus. They also stressed that theirs is the only authorized vaccine that requires just a single dose, and that it can be shipped and stored at refrigerator, rather than extremely cold, temperatures, making it more accessible to most of the world. “Johnson & Johnson’s vaccine is central to the effort to end the pandemic,” Dr. Joanne Waldstreicher, the company’s chief medical officer told the committee. “Our vaccine provides access to people who are underserved as well as people who typically face barriers in accessing health care services. Our concern is that with continued restriction of the vaccine we are not just delaying vaccination but potentially leaving unvaccinated a portion of the U.S. If the unvaccinated population is large enough, that could risk us reaching herd immunity.”
Waldstreich said the company favored adding a warning label about the risk of clotting, similar to the way the risk of anaphylaxis is now included in the label for the mRNA vaccines from Pfizer-BioNTech and Moderna.
Throughout the day, members of the committee noted that the data seemed to show the risk of clotting was rare, and that benefits of vaccination with the J&J shot outweighed that risk. But they debated over how to warn people—especially younger women—of the potentially serious side effect. Some favored wording that highlighted the risk specifically, noting that women under age 50 should be given the choice of another vaccine. That’s how the U.K .has decided to roll out the AstraZeneca vaccine, giving people under 30 the choice to get an alternative shot. Other committee members argued that specifically featuring the blood clotting would be inconsistent with the way other side effects for any vaccine, including the other COVID-19 vaccines, are handled; they said that blood clotting risks should be part of the already FDA-approved language, as follows:
“Reports of adverse events following use of the Janssen COVID-19 vaccine under emergency use authorization suggest an increased risk of thrombosis involving cerebral venous sinuses and other sites … combined with thrombocytopenia and with the onset of symptoms approximately one to two weeks after vaccination. Most cases of thrombosis with thrombocytopenia reported following the Janssen COVID-19 vaccine have occurred in females ages 18 through 49 years; some have been fatal. Specific risk factors for thrombosis with thrombocytopenia following the Janssen COVID-19 vaccine and the level of potential excess risk due to vaccination are under investigation. Based on currently available evidence, a causal relationship between thrombosis with thrombocytopenia and the Janssen COVID-19 vaccine is plausible…Recipients of the Janssen vaccine should be instructed to seek immediate medical attention if they develop shortness of breath, chest pain, leg swelling, persistent abdominal pain, neurological symptoms (including severe or persistent headaches or blurred vision), or petechiae beyond the site of vaccination.”
A lay version of that warning is included in the fact sheets that people who get vaccinated receive when they get their shot.
Dr. Sarah Long, professor of pediatrics at Drexel University College of Medicine, was one of the four members who voted against the recommendation. “I did not object to the recommendation,” she told the committee in explaining her vote. “I objected to the absence of any kind of guidance from us. I’m very sorry we haven’t chosen to put up front the knowledge we have that this unique, clustered side effect is almost certainly related to the vaccine and that there are options.”
Now it will be up to the CDC, the state public health departments and individual providers to inform people of the risks of the shot. The CDC is planning on publishing the updated EUA warning both on its website as well as in its weekly MMWR publication on April 27, and fact sheets for providers and people receiving the vaccine have already been updated and will be distributed in coming days.
The committee members discussed the burden that would place on some providers, especially those with smaller vaccination programs, who would now, ideally, have to stock two different vaccines in case some people decide against getting the J&J shot. They also considered the possibility that some women uncomfortable with getting J&J shot would end up not getting vaccinated or delaying their vaccination entirely if another option isn’t available immediately. “It places upon us who are making this vaccine available and distributing it, the responsibility to make sure the public is informed about the risk,” said Dr. Jose Romero, professor of pediatrics at University of Arkansas, director of Arkansas department of health, and chair of the committee. “Our responsibility as clinicians is to make sure women understand this risk and when possible, that they have alternatives at the same time that we are administering the vaccine.”