While experience so far with COVID vaccines shows that some are associated with very rare, early side effects, experts say they have confidence about the long-term safety of these vaccines.
That's because past experience shows that severe side effects from vaccines most often appear within a time frame of about 6 weeks after vaccination, according to Paul Offit, MD, director of the Vaccine Education Center at Children's Hospital of Philadelphia and a member of the FDA's Vaccines and Related Biological Products Advisory Committee (VRBPAC).
"If you look historically at severe vaccine safety problems, they have occurred about 6 weeks after getting a dose. I can't think of an example of a severe side effect that isn't seen within this time frame after vaccination. I know of no precedent of a long-term effect that comes up 5 or 10 years later," Offit told 鶹ý.
He noted that safety issues seen so far with COVID-19 vaccines have followed the pattern seen with past vaccines. Rare blood clots reported with the Johnson & Johnson vaccine occurred within 2 weeks of vaccination, and myocarditis reported with mRNA vaccines occurred within 4 days of dosage.
Offit added that the pathogenesis of the myocarditis side effect is still unclear, but if it involves an autoimmune mechanism, "it's the world's shortest-lived autoimmune response."
Cases are often mild and easily treatable with common anti-inflammatories such as ibuprofen or corticosteroids, with symptom resolution in most patients within 2 days to 1 week, according to a recent published in Pediatrics.
Comparison with Other Vaccines
Offit cited several examples of very rare side effects reported with other vaccines that provide a basis on which to guide current opinion about the safety of COVID-19 vaccines.
One example is reported within 1-4 weeks after receiving a live-attenuated oral polio vaccine that had reverted back to wild-type virus. Offit said these events were so rare, occurring at a rate of one in 2.4 million people, that they would not have cropped up in pre-licensure trials. The oral vaccine involved in these events is no longer used in the U.S., where an inactivated polio vaccine has been used since 2000.
A second example, he noted, is the , another live-attenuated vaccine, which has been associated with swelling of the brain or spinal cord in infants under age 6 months (for whom the vaccine is not recommended). More rarely, this adverse effect has also been reported in people over age 6 months, with onset 2-3 weeks after vaccination. The yellow fever vaccine has also been associated with very rare viscerotropic disease and , caused by viral replication and dissemination throughout the body. Onset is usually less than 1 week after vaccination, often within 3 days.
Other examples include transient thrombocytopenia 1-3 weeks after receiving the measles, mumps, and rubella vaccine, and narcolepsy within 7 weeks of vaccination for H1N1. The latter occurred in about one in 55,000 people after receiving a dose of one particular type of influenza vaccine used in Finland.
Offit said molecular mimicry was involved, meaning the vaccine involved in these cases of narcolepsy contained a greater amount of flu nucleoprotein, which mimicked a protein associated with wakefulness found on the surface of the hippocampus.
"There's no analogy for that with COVID-19 vaccines," he said.
Rare cases of Guillain-Barré syndrome were also associated with influenza vaccination in the 1970s, almost all of which occurred within 8 weeks of vaccination. However, studies have not confirmed vaccination as a cause of Guillain-Barré syndrome; the disorder also occurs after natural influenza infection, at a rate 17 times higher than reported in post-vaccination cases, he noted.
Concerns About New Technology
Concerns have also been raised about whether the newer technology used in current COVID-19 vaccines could lead to unknown side effects down the road.
Offit said it is valid to extrapolate what is known about the long-term safety of older vaccines to the newer technology, because the COVID-19 vaccines all rely on a common final pathway: introduction of a protein to which the immune system mounts a response.
The mRNA vaccines and viral vector vaccines both work on the principle of delivering genetic material that instructs the host cell to produce the spike protein. That principle is "not much different" than other vaccines, like hepatitis B and HPV protein subunit vaccines, he explained.
"Although the strategy is novel, the notion of introducing a foreign viral protein to the immune system is not novel. I can't imagine that this protein would do anything different than what we would see with any viral protein," Offit said.
As for other components of these vaccines, Offit said he does not believe these are cause for concern. For example, the lipid nanoparticle capsule used in the mRNA vaccines dissolves "fairly quickly" once it enters the cell, and the adenoviral vector used in the J&J and AstraZeneca vaccines has been genetically engineered to be nonreplicating.
"I can't imagine any long-term effects these nonreplicating viral vectors could have," he said.