Is COVID Vaccine Hesitancy Just Needle Phobia?

F. Perry Wilson, MD, MSCE


January 19, 2022

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.

One thing I've always wondered as I think about the anti-vaccination movement is: Why vaccines? Like, of all the medications out there, why do vaccines seem to engender so much more passion and outcry than anything else?

There are some obvious answers. Mandates, for one — there are few other medications that you are required to take as part of your job. Maybe if you squint, you could argue that the fluoridation of water is a sort of mandate, and I guess there are always people up in arms about that. But you don't see too many folks complaining about the iodization of salt to prevent goiter or the enrichment of flour to prevent B-vitamin deficiency.

There's the fact that you give vaccines to healthy people. Most medicines are given to treat something — at least, at first blush. In reality, we give plenty of medicines (statins come to mind) to prevent disease. Of course, the people we give them to are at risk for the disease, but, well, we're all at risk for infection.

But sometimes I wonder if part of the reasons vaccines cause so much emotion is their mode of delivery: the injection.

It hurts, of course; no one likes getting a shot. But maybe there's more than that — a psychological feeling of violation that people are hesitant to put words to.

A scoping study in Health Psychology in 2018, before the COVID era, tried to get to the bottom of this. They found that three psychological factors explained much more anti-vaccination attitude than demographics, education, or socioeconomic status. Those factors were:

  • Conspiratorial thinking;

  • Individualistic outlook; and

  • Disgust toward blood and needles.

We don't talk too much about the fear of needles, but it honestly may be the elephant in the room here. What got me thinking about this was this study, appearing in JAMA Network Open, that looks at the effects of placebo in randomized trials of vaccination. What struck me most was the startlingly high rates of adverse responses to placebos — often called the "nocebo" effect. Remember, vaccine trials occur in healthy individuals; the placebo adverse event rate should honestly be pretty low.

There have been a slew of randomized trials of COVID vaccines — though not all have reported on adverse events to the same degree of detail. This paper combines the results of 12 studies including 45,380 patients to determine just how common those nocebo effects are.

As you might expect, individuals in both the placebo and vaccine groups reported adverse events. But there's much to be learned within those event rates.


Look at the rate of systemic adverse events (things like fatigue, fever, and headache) in the placebo arm vs the vaccine arm after dose 1 and compare that with the rate of local adverse events (like arm pain).

Systemic adverse events are much more strongly affected by the nocebo effect. In fact, this analysis suggests that 76% of the reported systemic adverse events in the vaccine group are caused by the nocebo effect, at least after dose 1.

That goes down a bit after dose 2, but 50% of the systemic adverse events can be attributed to nocebo even after dose 2.


Systemic adverse events are more common than local injection site reactions with placebos because none of us feel 100% perfect all the time. We all get random headaches, aches and pains, and fatigue just by living our lives. But it's quite unusual for us to have a painful left deltoid unless something inflammatory has recently been stuck in there.

You may expect that nocebo effects are more mild than true vaccine adverse reactions, but a substantial portion of placebo adverse events were graded as stage 2 or stage 3 — similar proportions to the vaccine group — at least after the first dose.


What's the importance of all of this? For one thing, it helps us to be cautious when we get anecdotal reports of postvaccine adverse events. The placebo data remind us that bad things happen, and not all of them can be attributed to the vaccine itself. In fact, individuals are likely primed to look for adverse events after any injection because the act of injecting something into the body is unusual and aversive.

More than that, though, the sheer magnitude of the rates of placebo-linked adverse events in vaccine trials remind us that there is something different about injections — something that, for some of us at least, a deep part of our psyche rebels against. Perhaps that understanding can lead to new insights to address those who remain vaccine hesitant. I'm interested to see what happens when intranasal COVID vaccines are introduced, for example.

Until then, we have what we have: several effective injectable vaccines. And while we tend to think that those who choose not to receive them are ill-informed or bad at interpreting risks and benefits, it behooves us to remember that motivations can sometimes run much deeper.

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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