Subtitle: The risk of stroke seems to apply to Pfizer’s bivalent mRNA + high-dose or adjuvanted influenza co-vaccination only.
It began with the Centers for Disease Control and Prevention (CDC)’s and Food and Drug Administration (FDA)’s recent announcement (13 Jan) of a safety signal of increased stroke risk following the bivalent mRNA vaccine in those over 65 years. That’s a bold move, per their statement that “transparency and vaccine safety are top priorities.”
Obviously, some parties have taken this information out of context, as conclusive evidence of stroke-causing vaccines. Should the CDC and FDA not make this announcement then? I don’t believe so, for it might backfire as evidence of hiding info from the public. They might have intended their announcement as a pre-bunking of mis- or disinformation.
That said, let’s explore the uncomfortable relationship between stroke and Covid vaccines.
What the CDC and FDA announced
Let’s briefly go through what was announced.
Because of the widespread use of the updated Covid-19 bivalent mRNA vaccine, the CDC’s Vaccine Safety Datalink (VSD) surveillance database performed additional investigation on vaccine safety, specifically on ischemic stroke in those 65 years and older.
The CDC then admitted that this group of seniors was more likely to have an ischemic stroke in the 21 days after vaccination compared to 22–42 days after vaccination with Pfizer’s mRNA vaccine (bivalent), but not Moderna’s mRNA vaccine (bivalent).
But the CDC assured that such stroke signal was not detected from other surveillance systems, such as the Centers for Medicare and Medicaid Services database, Veterans Affairs database, Vaccine Adverse Event Reporting System (VAERS), and Pfizer-BioNTech’s global safety database, as well as surveillance systems from other countries. As a result, the CDC recommends no changes in current vaccination practice.
“Although the totality of the data currently suggests that it is very unlikely that the signal in VSD represents a true clinical risk,” the CDC said, “we believe it is important to share this information with the public, as we have in the past, when one of our safety monitoring systems detects a signal.”
The CDC and FDA claimed they will monitor the situation for additional data from the vaccine surveillance systems. They also planned to present these data at the upcoming January 26 meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee.
What the FDA’s meeting discussed
Over three weeks have passed, and the meeting slides have been released.
The meeting began with a backdrop on the bivalent mRNA vaccine booster, first available in the U.S. in September 2022. As of 11 January 2023, 49.5 million doses of bivalent mRNA vaccine were administered in those over 5 years in the U.S., including 21.4 million doses in those over 65 years.
Nicola Klein, MD, Ph.D., a vaccinology expert at Kaiser Permanente, did the preliminary analyses of ischemic stroke after Pfizer bivalent mRNA vaccination in Vaccine Safety Datalink (VSD).
VSD was first established in 1990 as a collaborative project between the CDC and nine other healthcare organizations, covering the electronic health records of about 12.5 million people across the U.S.
Klein used vaccinated concurrent comparators, where the risk of ischemic stroke at 1–21 days after a bivalent mRNA vaccination is compared to said risk at 22–42 days post-vaccination. This design was used because recent vaccinees should be more similar to current vaccinees than to non-vaccinees, thus minimizing potential confounders, such as genetics and behavior. All analyses were also adjusted for age, sex, race or ethnicity, VSD site, calendar time (days), and seasonality (time). That said, Klein also repeated the analyses with unvaccinated and historical controls.
Results found 1.47 times (47%) increased risk of ischemic stroke at 1–21 days compared to 22–42 days after Pfizer’s bivalent mRNA vaccination. The risk is statistically significant (p = .005), and the 95% confidence interval ranges from 1.11 to 1.95, indicating 11% to 95% increased risk at the tails of the distribution (Figure 1).
Additional analyses showed that the statistical signal of increased stroke risk persisted but slowly decreased over 7 weeks. And that increased stroke risk was mainly driven by 11–22 days post-vaccination, reaching a peak of 15–19 cases per 1 million person-days (Figure 2).
The person-days unit means that if we follow 1 million people for a day — or 47,620 people for 3 weeks (47,620*21 days =1M) — we would see 15–19 cases of post-bivalent vaccine stroke. This translates to a post-bivalent vaccine stroke incidence of 0.0015%–0.0019% in a year or 0.03%–0.04% in 3 weeks.
Klein further reviewed a subset of post-bivalent mRNA vaccine stroke cases (n=22) from one VSD site:
- The median age was 77.5 years, and none had a history of stroke.
- 5 cases (23%) had a history of SARS-CoV-2 infection, but only 1 case had it within the last 6 months. None had a known recent exposure to SARS-CoV-2.
- 14 cases (64%) had influenza co-vaccination on the same day.
- 13 cases (59%) were discharged home; 4 cases (18%) were discharged home with residual health issues; 2 cases (9%) were discharged to a nursing facility; and 3 cases (14%) died.
- Among the 3 fatal cases, one died 1 month after a stroke, another died from cardiac arrest 2.5 months after brain surgery, and the last stroke case died from cancer-related complications. So, only 2 cases (9%) of death are likely related to post-bivalent vaccine stroke.
Klein then analyzed if influenza co-vaccination affected the stroke risk of bivalent-vaccinated individuals. Interestingly, bivalent mRNA + influenza (high dose or adjuvanted) vaccination posed a 2-times higher risk of stroke in the first 1–21 days compared to 22–42 days (Figure 3).
But no changes in stroke risk were seen in bivalent mRNA without influenza vaccination, bivalent mRNA + standard-dose influenza vaccination, or influenza vaccination alone.
This analysis suggests that high immune responses from strong vaccination stimuli (bivalent mRNA + high-dose or adjuvanted influenza vaccines) increase the risk of stroke. The risk faded if the standard-dose influenza vaccine was used instead. The risk also vanished if no influenza or no bivalent mRNA vaccine was given.
Klein then repeated the analysis with unboosted (bivalent-unvaccinated) individuals as controls. A 1.24-times lower risk of ischemic stroke was noted at 22–42 days post-bivalent vaccination compared to the non-bivalent group. No significant difference was noted in the 1–21 days post-bivalent risk interval. Many reasons can be postulated for this discrepancy, such as behavioral differences where boosted individuals might have chosen to get boosted because they’re aware of their poorer health.
Klein also raised some concerns about her analyses. For one, the small number of stroke cases may limit the accuracy of risk analyses, especially for Moderna’s bivalent booster. Second, some confounders may have gone unmeasured, most notably behavioral differences. Third, background asymptomatic SARS-CoV-2 infections may have been missed.
Klein then closed by suggesting the continual surveillance of stroke risk after bivalent mRNA vaccination in both VSD and other surveillance systems, as well as further studies on the effects of bivalent mRNA and influenza co-vaccination. In the end, Klein and the CDC still recommend bivalent mRNA vaccines as boosters to those who are eligible.
But judging from Klein’s analyses, it may be wise to avoid getting the high-dose or adjuvanted influenza vaccine the same day as getting the bivalent mRNA vaccine booster if you are 65 and above. Doing so may possibly overstimulate the immune system and contribute to stroke.
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