Covid-19 Boosters Aren’t for Everyone
If you’re healthy and young, a third shot gives no benefit, so it isn’t worth even the small risk.
By Michael Segal
Nov. 3, 2021 12:20 pm ET
Healthy people in their 20s have been asking me about getting the third shot of the Covid-19 mRNA vaccines, recently authorized for older people. I’ve advised caution. More vaccine isn’t always better.
Doctors think of drug dosing using the metaphor of a “therapeutic window.” The bottom of the window is the lowest effective dose. The top is the dose at which the side effects become unacceptable. We aim to keep the dose within the therapeutic window.
When the Pfizer and Moderna vaccines were first released, a second shot got 95% of patients into the therapeutic window, defined by total absence of symptoms. In the months since then, some of those people have dropped below the bottom of this therapeutic window because of a combination of fading immunity and the arrival of the Delta variant. Thus the case for boosters: A Pfizer study demonstrates that a third shot, administered some 11 months after the second, reduces symptomatic infections by 96% compared with those who had two shots.
So why not give everyone a third shot? Many people who got two shots are still in the therapeutic window and wouldn’t benefit from a third shot. For them, a booster would risk gratuitous inflammation that would push them above the window. The prospect of such inflammation wasn’t a deal breaker with the second shot. Months of follow-up revealed instances of heart inflammation, especially in young male patients, but these were rare and almost always mild and transient, and Covid itself can produce far worse heart inflammation. Other symptoms of inflammation, such as fever, fatigue and headache were far more common but lasted for only a day or two.
There could be other, more serious effects of inflammation that would take years to become apparent. In other contexts, strong inflammation has been shown to disrupt the “blood-brain barrier” and contribute to the progression of Alzheimer’s disease. That possibility isn’t a reasonable argument against a second shot because the inflammation from Covid itself can be far stronger, and the second shot reduces that risk by providing solid protection against serious disease.
For third shots, the calculation changes. A booster makes sense for most older people and for the immunocompromised because they tended to get lower efficacy and little inflammation from the second shot. A third shot puts them back into the therapeutic window. But healthy young people typically had good efficacy from the two-shot regimen, and many had strong inflammation.
The Food and Drug Administration and the Centers for Disease Control and Prevention struggled with such issues and recommended a third shot for the elderly and the immunocompromised, but not for healthy young people. Advisory committee members suggested that further research was needed to refine these initial recommendations.
Some such research will be at the population level, advising about particular ages and vaccines. Other recommendations will be more personalized, drawing on many decades of assessing immunity against other diseases. When I began my clinical training in the 1980s, our group of new doctors took a blood test to assess immunity to diseases for which we could be vaccinated. Similarly, more research using blood tests for Covid immunity and questionnaires about the risk of inflammation could allow us to assess whether further shots would move a particular patient in or out of the therapeutic window.
Personalized recommendations are particularly important for the more than 100 million Americans who have already recovered from Covid. Their immunity and risk of inflammation from vaccines is variable. But when health officials refuse to take account of natural immunity, they neglect the needs and concerns of a large segment of the population and give the public a reason to think experts are not conveying the whole truth.
We also need answers to other questions about the therapeutic window for vaccines, such as whether taking anti-inflammatory drugs after vaccination is good because it reduces inflammation or bad because it could reduce the vaccine’s effectiveness.
Radio hosts often advise listeners to “do your own research.” What we really need is research that gives the CDC and FDA the data needed to refine their initial recommendations on third shots. The recommendations that will be most acceptable to the populace are the ones that promote trust by helping assess whether a particular patient would benefit from the shot.
Dr. Segal is a neurologist and neuroscientist.
