CDC, FDA Investigating Potential—But 'Unlikely'—Link Between Pfizer Booster and Stroke Risk

The Centers for Disease Control and Prevention and the Food and Drug Administration are investigating a possible—but “very unlikely”—link between Pfizer-BioNtech’s updated COVID booster and ischemic stroke in people ages 65 and older, the agencies announced Friday.

Federal officials said that the safety signal likely does not indicate a “true clinical risk,” and advised no changes to the current vaccine recommendations, which state that everyone 6 months or older stay up-to-date on COVID-19 vaccinations.

The safety signal stemmed from data collected from the CDC’s Vaccine Safety Datalink (VSD), a near real-time surveillance system that includes 13 healthcare sites from across the country. The preliminary data—which showed that seniors may be more likely to have an ischemic stroke in the 21 days following a Pfizer booster, compared with the 22-41 days after vaccination—met the criteria for additional investigation.

This preliminary signal was not detected for Moderna’s bivalent COVID vaccine, officials said. They also noted that none of the other surveillance systems have shown a similar signal, nor have analyses or studies validated the signal.

Safety Signal Sparks Further Investigation

In an effort to be transparent with the public, the CDC shared the safety signal to announce further investigation into a potential link between Pfizer’s COVID booster and stroke risk among seniors.

Ultimately, this will allow the CDC to determine if the booster is definitively associated with an increased risk of stroke, or if there’s some other explanation for the slight blip in the data, said Amesh Adalja, MD, infectious disease physician and senior scholar at the Johns Hopkins Center for Health Security.

“Data doesn’t always tell the whole story,” he told Health. “They saw a signal that was above the threshold that they had set for action, which then prompts them to try and investigate by querying the other databases, and trying to understand if this signal actually points to a causal linkage, rather than a mere coincidence.”

The CDC and FDA will continue to evaluate data from the VSD along with other surveillance systems, and discuss their findings at an upcoming meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee on January 26. At that time, federal officials will also discuss recommendations for COVID vaccination going forward.

Surveillance Systems Working as Intended

The data collected by the VSD—which ultimately sparked the safety signal—shows that federal agencies’ surveillance systems are working as they should.

VSD, which began in 1990, is a collaborative project between the CDC’s Immunization Safety Office, integrated health care organizations, and networks across the U.S., and relies heavily on large amounts of data.

“We have a team of people at the CDC, but the data actually come from healthcare organizations around the country,” Katherine Yih, PhD, MPH, a principal investigator of the VSD site at Harvard Pilgrim Health Care Institute, told Health.

The patient populations from all of those organizations across the country add up to more than 12 million people, said Yih, adding that “it’s possible to do really good, statistically-powered studies using the data from that nice, big patient population.”

Each week, data from the various VSD sites come in and the new batch is analyzed, Yih said. That allows for potential issues or outliers to be identified sooner rather than later, she added. If something does seem off, it can be further investigated with formal epidemiological studies.

“This is the system working correctly,” said Dr. Adalja. “A signal comes up from one of the databases, they run it down and understand whether or not this is something real that people need to be worried about.”

In fact, Yih and Dr. Adalja added, these safety signals crop up from time to time, and certainly have in the past. They’re usually ruled out, but with the extra attention on COVID and bivalent boosters, this safety signal is now making headlines, said Dr. Adalja.

“In the past, we would often take a bit more time to investigate signals arising during vaccine safety surveillance before going public, knowing that such statistical signals can turn out to be [false],” Yih said in a statement. “But in the current climate, there’s a lot of scrutiny of COVID-19 vaccine safety and of CDC. So CDC is making a great effort to be transparent with the public.”

Officials, Experts Still Recommend COVID Boosters

Although the CDC and FDA are still investigating the safety signal, federal agencies have not changed their recommendations for COVID vaccination: All people ages 6 months and older are urged to stay up-to-date on their vaccines, including through use of the booster shots.

But this new information may only exacerbate vaccine hesitancy among Americans, said Dr. Adalja. Only about 40% of adults have gotten or are planning to get a bivalent booster, COVID cases are ticking back up, and a new highly transmissible variant is picking up steam.

“I can understand that the CDC’s statement has unsettled some people, even those who were not worried about COVID-19 vaccine safety previously,” said Yih. “We will have a clearer idea of whether this statistical signal is anything to worry about within the next couple of weeks. For now, though, I am not worried.”

David Diemert, MD, a professor of medicine and director of the George Washington University Vaccine Research Unit, also believes that the safety signal picked up by the CDC and FDA is likely “just a blip.”

“[Increased risk of stroke] wasn’t seen at all with the prototype, the original version of the vaccine. And [...] it hasn’t been seen with the Moderna bivalent vaccine,” he said. “It hasn’t been reported from any other country, and millions of doses have been given already.”

In a statement to The New York Times, Pfizer also said that its vaccine remains safe for public use. “There is no evidence to conclude that ischemic stroke is associated with the use of the companies’ Covid-19 vaccines,” the statement said.

Ultimately, experts agree that there’s no real reason to delay or avoid getting the updated booster.

“The potential benefit still far outweighs the possible risk that has yet to be definitively proven and which might not even exist,” said Dr. Diemert. “[The bivalent vaccine] greatly reduces the risk of death, greatly reduces the risk of hospitalization—still, even now with Omicron and the newer variants. So even with a possible added risk, it still is outweighed by the incredible benefits.”