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The pause is lifted, and Johnson & Johnson's COVID-19 vaccine is once again recommended for adults, according to the CDC's Advisory Committee on Immunization Practices (ACIP).

In a 10-4 vote, with one abstention, ACIP said in updated interim guidance that the Johnson & Johnson vaccine is recommended under FDA emergency use authorization (EUA) for all adults.

They ultimately decided that including a separate warning on the vaccine, as well as in an FDA EUA fact sheet and materials on the CDC website, was sufficient. One choice the committee chose not to vote on would have added language that women under age 50 should be aware of the increased risks of rare clotting events, and may opt for a different authorized COVID-19 vaccine. The committee agreed that any further qualifiers would be too cumbersome for local jurisdictions to implement and might contribute to vaccine hesitancy.

Johnson & Johnson researchers unveiled a proposed warning that the FDA agreed to add to the vaccine's current EUA. It warns about the risks of thrombosis with thrombocytopenia syndrome (TTS), and recommends that clinicians consult with the published for diagnosis and treatment of the condition.

ACIP member Grace Lee, MD, of Stanford University School of Medicine, said that putting a qualifier for any demographic group would be "extremely confusing," because every ACIP recommendation "is a benefit/risk balance."

The committee believed that the benefits of one-dose vaccination outweighed the risks, as it makes this vaccine available for vulnerable populations, including people experiencing homelessness, incarcerated populations, and home-bound populations.

The "no" votes came from members who felt that younger women would not be adequately informed about the risks of this rare adverse event by a warning label and EUA fact sheet.

"I did not object to the recommendation. I objected to the absence of any kind of guidance from us," said ACIP member, Sarah Long, MD, of Drexel University College of Medicine in Philadelphia. "This is an age group that is most at risk and is getting the vaccine predominantly to save other people's lives. I'm very sorry we haven't chosen to put up front the knowledge we have that ... there are options."

ACIP chair, José Romero, MD, ultimately voted yes, but added that he thought there was a bit of a "selective interpretation" in terms of how much younger women would be informed. He urged vaccination sites to have a second vaccine available so that younger women are not forced to shop for vaccines.

"These events are rare, but they are serious," Romero said.

The American Medical Association (AMA) reiterated their support for the Johnson & Johnson vaccine and pledged to help inform patients about the rare adverse events.

"The AMA will continue to work with the FDA and the [CDC] to ensure physicians and patients are aware of the rare, but increased risk of [TTS] in women under the age of 50, as well as the appropriate treatment, so they can act quickly," said AMA president Susan Bailey, MD, in a statement.

On April 13, CDC and FDA agreed to a "pause" on use of Johnson & Johnson's COVID-19 vaccine out of an abundance of caution. At that point, there were six cases of cerebral venous sinus thrombosis (CVST) with thrombocytopenia, one fatal. ACIP met on April 14, but agreed to wait to vote until more data accrued on the available cases, including potential risk factors.

As of April 21, the number of cases rose to 15, with three deaths. Seven patients remain hospitalized, including four in the ICU, while five were discharged home.

Thirteen of these cases were in women ages 18-49, with two in women older than 50. Based on these data, Tom Shimabukuro, MD, of the CDC, estimated that the rate of TTS was 7.0 per million doses in younger women, and 0.9 per million in older women. Seven cases of 15 were among women ages 30-39.

While all cases were in women, Shimabukuro noted that some data were still under review, "including potentially male cases," although as of now, there were no cases reported in men.

Median patient age was 37, with a median time to onset of 8 days following vaccination. While 12 cases were CVST, three were other forms of thrombosis. Seven patients had obesity, while two patients apiece reported oral contraceptive use, hypothyroidism, or hypertension. No patients had established coagulation disorders.

All patients had thrombocytopenia, with 10 patients having severe thrombocytopenia, or platelet levels under 50,000. Of the 11 patients where a platelet factor 4 heparin-induced thrombocytopenia ELISA antibody test was performed, all were positive. Four patients did not have available results. Seven patients with CVST experienced intracerebral hemorrhage.

Non-heparin anticoagulants were used to treat 12 patients and intravenous immunoglobulin to treat eight patients, while platelet transfusion was used for seven patients and heparin for six patients. Shimabukuro noted that the six patients received heparin prior to the about treating this condition.

Shimabukuro said that cases under investigation may increase, as researchers plan to broaden their case definition to harmonize with the draft Brighton Collaboration case definition for TTS. This could include other thrombotic events, including venous thromboembolism, deep vein thrombosis, pulmonary embolism, ischemic stroke, and acute myocardial infarction.

CDC and FDA released saying vaccinations with Johnson & Johnson's COVID-19 vaccine can resume. At a press conference, CDC and FDA officials said that would likely be on Saturday morning.

CDC Director Rochelle Walensky, MD, praised the decision to resume vaccination and the time taken to fully investigate this issue.

"I think this pause conveyed we are taking every one of these needles in haystacks we find seriously," she said.

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