Instances of stroke following receipt of Pfizer’s new booster in the elderly may be connected to the influenza vaccine, officials said on Jan. 26.

One-hundred thirty cases of ischemic stroke, which can be deadly, were recorded among people aged 65 or older within 21 days of a bivalent Pfizer booster, the U.S. Food and Drug Administration’s Vaccines and Related Biological Products Advisory Committee heard on Thursday.

That was higher than the 92 cases recorded in the 22- to 42-day window following vaccination, triggering a safety signal.

The U.S. Centers for Disease Control and Prevention (CDC) and the administration (FDA) revealed the signal on Jan. 13 but had not said how many cases were recorded from the U.S. government’s Vaccine Safety Datalink surveillance system, which contains records from 12.5 million people across 11 sites.

A preliminary review of medical records at one site, which saw 24 ischemic stroke cases in the three weeks following Pfizer vaccination, revealed that a majority of the people who suffered a stroke had an influenza vaccine administered on the same day as the COVID-19 vaccine.

None of the patients had a history of stroke or transient ischemic attack, which is similar to a stroke and could be a non-vaccine cause of ischemic stroke.

Three of the patients died, including a man who perished one month after the stroke. His death was determined to likely be related to the health event.

Overall, 40 cases of ischemic stroke following both COVID-19 and flu vaccination were identified among people who suffered stroke through Dec. 17, 2022. That post-signal analyses heightened the safety signal, which is a sign a vaccine may cause a condition. Only 34.5 cases were expected based on background rates.

There were 60 cases among elderly people who received a bivalent COVID-19 vaccine without receiving a flu vaccine on the same day. That number did not meet the definition of a signal.

Officials decided to compare the cases recorded among boosted people one to 21 days after vaccination with boosted people 22 to 42 days after vaccination for the primary analysis. The rationale given was that people who recently received a vaccine were “expected to be more similar to current vaccinees than unvaccinated individuals.”

Officials also revealed that they excluded post-vaccination ischemic stroke cases if a person had a personal history of certain conditions, including transient ischemic attack or atrial fibrillation, also known as irregular heartbeat.

The new information came from a set of slides that Dr. Tom Shimabukuro, a CDC official, and Dr. Nicola Klein, a Kaiser Permanente official who works closely with the CDC, presented to the FDA’s vaccine advisory panel.

“CDC and FDA are engaged in epidemiologic analyses regarding coadministration of COVID-19 mRNA bivalent booster and flu vaccine,” one slide stated, following the detection of a “significant cluster” of post-vaccination cases of the ischemic stroke.

The CDC and FDA said previously that an examination of other surveillance systems showed no signal of ischemic stroke for the bivalent boosters but failed to mention that an analysis of reports to the Vaccine Adverse Event Reporting System, which the agencies co-manage, for the original Pfizer and Moderna COVID-19 vaccines triggered the signal for ischemic stroke and hundreds of other adverse events. Both the original vaccines are still administered in the United States; the bivalents can only be obtained as boosters.

Pfizer and its partner BioNTech said in a recent joint statement that the companies were made aware of “limited reports of ischemic stroke” observed in the Vaccine Safety DataLink system.

“Neither Pfizer and BioNTech nor the CDC or the U.S. Food and Drug Administration (FDA) have observed similar findings across numerous other monitoring systems in the U.S. and globally and there is no evidence to conclude that ischemic stroke is associated with the use of the companies’ COVID-19 vaccines,” the companies stated.

Israel and the European Union have said that they have not detected a signal for ischemic stroke following bivalent vaccination. European officials said they also looked at Pfizer’s original vaccine.

Signal First Identified in 2022

The slides also showed that the safety signal from the Vaccine Safety Datalink was first identified in 2022.

The first time the condition met the signal was Nov. 27, 2022, one slide showed. It did not stop meeting the signal as of Jan. 8, 2023.

The signal has been “persistent for 7 weeks,” one slide stated.

While the rate ratio, or the result of the analyses, “has slowly attenuated from 1.92 to 1.47,” it “has continued to meet signaling criteria,” the slides acknowledged.

The CDC did not immediately respond to a request for comment.

Klein said during the meeting that during the past week, the rate diminished enough that it no longer met the signal.

Officials said they would continue to monitor data from the datalink system, consider expanding the record review to all system sites, and look at data from other systems to better understand the possible role of flu vaccination with COVID-19 vaccination as well as examine the indication of a decreased rate of stroke in the three to six weeks following vaccination.