'Game the System' to Boost Vaccination Rates -- Why Not?

F. Perry Wilson, MD, MSCE


October 20, 2021

This transcript has been edited for clarity.

Welcome to Impact Factor, your weekly dose of commentary on a new medical study. I'm Dr F. Perry Wilson of the Yale School of Medicine.

Like many of you in healthcare, I've been fielding questions from friends, family members, and the public about COVID for the past, well, almost 2 years. And, broadly, they fit in just a few categories.

There are the "When will we go back to normal?" questions:

  • When can we stop wearing masks?

  • When can we go to the theater?

  • When will restaurants go back to full capacity?

  • When will the kids return to school?

  • When will the pandemic be over?

There are the "Is this safe?" questions:

  • Can I have my kid's birthday party inside?

  • Should I go to this wedding?

  • Is it okay to go to a concert if everyone is vaccinated?

  • Should my kids ride the bus?

There are the "Does [insert drug here] cure COVID?" questions:

And, of course, there are the vaccine questions. So many vaccine questions:

  • Does the vaccine actually prevent infection?

  • Does it prevent transmission?

  • Are vaccines safe?

  • Which is the "best" vaccine?

  • Should I be vaccinated?

  • Should my kids be vaccinated?

  • When can my kids be vaccinated?

  • Do mandates increase vaccination rates?

But a new flavor of the latter has been populating my emails and texts and social media messages lately, a subpopulation that I've come to think of as "gaming the system" questions:

  • Should I get a booster even though it's not recommended?

  • Should I get a booster with a different vaccine?

  • Should I shorten the time between dose 1 and dose 2?

  • Should I lengthen the time between dose 1 and dose 2?

These questions come from relatively well-informed people with reasonable concerns about the impact of COVID and the impact of vaccines. And the general theme is, can I do something different from everyone else to improve my chances of either a good response to the vaccine or to reduce my risk for side effects?

The ideas run the gamut. People ask about mixing and matching vaccines, delaying or shortening the dosing interval between doses 1 and 2, giving lower doses of vaccine, or using just a single dose. All of these are really interesting questions, but of course I have to give the same answer every time: I'm not really sure.

Take the dosing interval, for example. One individual emailed me with concerns about myocarditis from the mRNA vaccines. He had noted that some studies suggested that a longer dosing interval between doses 1 and 2 led to increased protection, and posited that therefore a shorter dosing interval, though perhaps less protective, would also have a lower degree of side effects.

Plausible? Sure. But I don't know. Myocarditis is rare as it is, and there are no studies tying dosing interval to the incidence of that side effect.

Mixing and matching vaccines was just endorsed by the FDA advisory panel, thanks largely to this NIH study which found higher antibody levels when a booster dose was given from a different manufacturer than the original dose — though to be fair, this was largely driven by those who received the J&J vaccine in the first place. This has led to people asking me if they should try to get Moderna after getting Pfizer, or vice versa. But again, we don't really know whether this confers any benefit. The NIH study was small — just 458 people — and antibody titers are not the same as protection level.

Nevertheless, I find the whole idea of custom vaccine regimens somewhat appealing as a method to convert the vaccine hesitant. Vaccine conspiracy theories, the nanobots, the magnetism, are appealing because they offer the allure of secret knowledge; nearly every conspiracy does. We all want to feel like we are in on the secret. Maybe these outside-the-box dosing strategies might work the same way. I think there is a natural human tendency to order off the secret menu, so to speak.

And, of course, the truth is that there may be a totally ideal dosing interval for the vaccines, or a perfect combination of vaccines that maximizes benefit while minimizing risk. But honestly, we don't know that yet, and in the absence of some truly massive trials we probably will never know that.

Frankly, the vaccines work well enough the way we've been giving them; there's not a huge incentive here to optimize at the margins. But hey, if it gets someone who is not vaccinated to get vaccinated, is it really so bad?

Look, more than 3 billion doses of COVID vaccine have been given around the world, almost entirely according to the boring old manufacturer instructions. And that's a lot of data with one hell of a safety and efficacy record. Gaming the system one way or another provides an illusion of control in what is an increasingly chaotic world. But it really is just an illusion. Of course, if the illusion of control is what it takes to get someone from the unvaccinated column to the vaccinated column, well, a bit of coloring outside the lines may be just what the doctor ordered.

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale's Clinical and Translational Research Accelerator. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and hosts a repository of his communication work at

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