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Only myocarditis/pericarditis and seizures occurred at higher rates in adolescents and children vaccinated for COVID-19 when compared with historical rates of those outcomes, according to an analysis of safety data from the FDA's Biologics Effectiveness and Safety (BEST) Initiative.

Data gathered from over 4 million children revealed that myocarditis or pericarditis occurred at higher rates than before the vaccines were introduced among 12- to 17-year-olds after receiving the original monovalent Pfizer-BioNTech BNT162b2 (Comirnaty) vaccine, Patricia Lloyd, PhD, ScM, of the FDA in Silver Spring, Maryland, and colleagues reported in .

Researchers also detected a statistical signal for seizures after vaccination with the BNT162b2 vaccine among children ages 2 to 4 years and with the Moderna mRNA-1273 (Spikevax) vaccine among children ages 2 to 5 years. The study found a total of 72 cases of seizures among these children, the majority of which were febrile seizures (71%). The median time between vaccination and seizure diagnosis was 2 days (range 1-5).

"The new statistical signal for seizure observed in our study should be interpreted with caution," Lloyd and study co-authors wrote, adding that further study is warranted. "Because febrile seizures can be common in young children for a variety of reasons, the analysis may have identified febrile seizures unrelated to the vaccination."

The analysis did not control for bias or confounding, and did not establish a causal relationship between vaccines and health outcomes, they noted.

In post hoc sensitivity analyses, a statistical signal for seizure was observed only after vaccination with mRNA-1273 when 2019 historical background rates were used. No statistical signal was observed when 2022 rates were used, the authors pointed out.

How worrisome is the statistical signal for seizure? Michael Smith, MD, division chief of Pediatric Infectious Diseases at Duke University School of Medicine in Durham, North Carolina, told 麻豆传媒 that he found the overall results of the analysis reassuring.

"Yes, [the study authors] found myocarditis and pericarditis, which is known. They found a potential increase of seizures after these vaccines that is undergoing further analysis," Smith said. "But for all of the other [safety] outcomes that they looked at, there was no association at all. This points to the overall safety of the vaccine[s]."

"We need to put this into perspective," William Schaffner, MD, an infectious diseases expert at Vanderbilt University in Nashville, Tennessee, told 麻豆传媒. "In this study, they actually were able to assess vaccine safety for rare events because they looked at over 4 million [vaccinated] children, so they're looking for needles in haystacks."

It is important to note that of 21 prespecified health outcomes that were monitored, only 15 warranted sequential testing, meaning a minimum of three cases accrued during the risk window. These outcomes were then evaluated to determine if the observed rate of those outcomes was higher when compared to historical rates. Of the 15, only myocarditis or pericarditis and seizures met the threshold for a statistical signal, the authors pointed out.

Other outcomes that did not meet the criteria for sequential testing included conditions such as multisystem inflammatory syndrome in children, unusual site thrombosis, acute myocardial infarction, and transverse myelitis, among others.

"Another thing that's important to realize is, to put it very colloquially, there's no free lunch," Schaffner commented.

"There is no single medication -- and I include aspirin -- and certainly no vaccine that isn't associated with at least some of these rare adverse events. That's just part of life," he said. "Balance that against what could happen if your child got COVID and these authors remind us ... that balance weighs very strongly in favor of vaccination."

Lloyd and colleagues noted that eight seizures had through 2022 in the Vaccine Adverse Events Reporting System (VAERS) database, of which six were afebrile. They pointed out that this low number of seizures was identified after approximately 1 million mRNA vaccinations had been administered in children ages 6 months to 5 years.

Lloyd and co-authors emphasized that the benefits and risks of COVID-19 vaccination continue to outweigh risks of COVID-19 infection in children.

This cohort study was an expansion of the initial safety surveillance data of the FDA's BEST Initiative of COVID-19 vaccines in children. The analysis evaluated 21 prespecified health outcomes after exposure to BNT162b2, mRNA-1273, or the Novavax (NVX-CoV2373) ancestral monovalent COVID-19 vaccines in children ages 6 months to 17 years. The study used near-real-time data gathered through February-April 2023 from three large commercial claims databases in the U.S. -- Optum, Carelon Research, and CVS Health. Increased rates of each health outcome after vaccination were compared with annual historical rates from all of 2019 and 2020, and from April through December 2020.

Among the 4,102,016 vaccinated children ages 6 months to 17 years included in the analysis, about half were male and over 95% lived in urban areas. A total of 8,444,344 monovalent COVID-19 vaccines were administered, the majority of which were BNT162b2 doses.

Because the data was from a commercially insured pediatric population, it did not represent all children in the U.S., the authors pointed out. Medical record review of the identified cases of myocarditis or pericarditis was limited and is currently under way for the seizure cases. Very few children ages 12 to 17 years received the NVX-CoV2373 vaccine and only 4,266 children between the ages of 5 and 17 received the mRNA-1273 vaccine, so conclusions could not be drawn about those vaccines in these age groups.

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