Do we know if the new RSV vaccines are safe?

Possible safety signals were very, very rare in the RSV vaccine trials, and no surprises have emerged with roughly 12 million Americans having received them so far.

Possible safety signals were very, very rare in the RSV vaccine trials, and no surprises have emerged with roughly 12 million Americans having received them so far.

There are two new vaccines available to prevent RSV and serious outcomes from RSV, both available in the US for adults aged 60 and up. Both were FDA-approved this year following large randomized clinical trials. The FDA’s and CDC’s independent vaccine advisory groups reviewed the trial data and decided that the safety and side effect profiles of these vaccinations are very low-risk, much lower than the risks of the disease they prevent. See this link for FDA data on Abrysvo from Pfizer and this one for Arexvy from GSK.

There were several trials of these vaccines which together involved tens of thousands of participants. The FDA makes decisions about whether to authorize drugs based on a careful assessment of the individual-level risks of taking the drug versus the risks of not taking the drug. CDC makes its recommendations on a similar basis, focusing more on population-level health including costs, non-clinical factors (like missed work/school), and health equity. In the case of both new RSV vaccines, the risks of not taking them far outweighed the risks of taking them. 

Risks of RSV

RSV causes thousands of hospitalizations every year among older adults and is a major cause of death for older adults. In the trials, RSV vaccination reduced the risk of getting RSV by at least 83% in the first season and 56% in the second season after vaccination. So, the risks of not getting vaccinated are pretty large. 

Evidence of safety in clinical trials

With the risks of NOT vaccinating in mind, we can turn to the risks of taking the RSV vaccinations. We’ll talk about what we know from the clinical trials first, and then turn to real-world data. 

Overall, in the clinical trials, there were very few serious health issues that could theoretically have been due to the new vaccines. In fact, they were so rare that it’s hard to know if they just occurred due to random chance or if there’s truly a slight increase in the risk of these after vaccination. 

Across all of the trials, there were two possible safety issues that were carefully reviewed by FDA’s advisory panel and CDC’s advisory panel. Five people (out of more than 38,000) had an acute neurological event after getting their vaccination. There were two cases of Guillain-Barré syndrome, one case of Miller-Fisher syndrome (which is similar to Guillain-Barré), one case of acute disseminated encephalomyelitis (an autoimmune condition involving swelling of the coating around nerve cells), and one case in which a pre-existing neurological condition got worse following vaccination. A second case of acute disseminated encephalitis was initially identified, but the diagnosis was later revised to other causes related to pre-existing conditions. Taken all together, that’s 0.01% who had a neurological event. Some of the trials where these events occurred were early-phase safety trials, so there was no placebo group to compare the risk to. That makes it very hard to know if this risk is higher than the typical population risk of these events overall. 

The second possible safety issue was an increased risk of atrial fibrillation following vaccination. 20 people in the vaccination groups experienced this condition, while 8 in the placebo groups experienced it (combined across both major phase 3 trials). Although 20 is obviously bigger than 8, these are both very small numbers in the context of how common atrial fibrillation is among older adults. Statistically, it’s not enough of a difference to know for sure if the risk of atrial fibrillation is truly higher following RSV vaccination or if the difference was just an unlucky chance. 

Evidence of safety since the approval of the RSV vaccines

Both manufacturers are required to continue monitoring their products for safety issues and report them to the FDA. CDC is also looking closely at their safety monitoring data to see if any true differences in the rates of neurological symptoms or atrial fibrillation arise. 

So far, 16% of people in the U.S. over age 60 have received one of these two new vaccines. That’s roughly 12-13 million older adults. Nothing indicating that RSV vaccination actually does increase the risk of these outcomes—or any other surprise—has emerged. And 12 million is a lot of people. Time may reveal that RSV vaccination confers no increased risk of neurological symptoms or atrial fibrillation at all. 

One thing we know for sure at this point is that IF there is any risk, it’s very, very small. Meanwhile, the risks of RSV to older adults are not small. Each season, an average of 6,500 older adults in the U.S. die of RSV infection.