COVID Vaccine Side Effects May Come From Your Expectations—Not the Shot

Potential COVID-19 vaccine side effects have been a big concern for people who are nervous to get the shot. However, new research has found that many of the side effects people report are actually just a placebo effect.

The study, which was published in JAMA Network Open, analyzed 12 articles that included data on side effects reported by 45,380 COVID-19 vaccine trial participants. Some of the people in the trial got a real COVID vaccine while others got a placebo: a shot that looked the same but did not have any actual COVID vaccine in it.

The researchers found that 35% of the people who got the placebo shot reported having systemic side effects after getting their first dose. After getting the second dose of the vaccine, 32% of the placebo group reported systemic side effects.

The most common symptoms were headache (19.6%) and fatigue (16.7%).

However, the people who got the real COVID vaccine reported more side effects than the people who got the placebo shot. The researchers found that after getting their first dose of the real vaccine:

• 46% of the people reported at least one systemic side effect
• 67% reported at least one “local” event (like injection site pain or swelling)

After getting their second dose of the vaccine:

• 61% of the people reported having systemic side effects
• 73% reported having local side effects 

The Placebo Effect

However, some of these side effects also happened in the placebo group. Since these people did not get the real COVID vaccine, that means that their side effects didn’t happen because of the shot. If a person has side effects from a placebo treatment, it’s called the placebo effect.

Therefore, the researchers estimated that the placebo effect was responsible for 76% of the side effects that the people in the placebo group reported after getting their first dose and 52% of the side effects they reported after getting their second dose.

The researchers used the term “nocebo” to describe what the people who received a placebo experienced. The “nocebo effect” is when a person’s expectations about experiencing something negative after a treatment (e.g., a vaccine side effect) make them more likely to have that negative experience.

The researchers concluded that their study “found that the rate of nocebo responses in placebo arms of COVID-19 vaccine trials was substantial.”

The ‘Nocebo Effect’ Is Common

Thomas Russo, MD, a professor and the chief of infectious disease at the University at Buffalo, told Verywell that the nocebo effect is common. That’s why it’s so important that when researchers are testing the efficacy of treatments like vaccines, they “run a control or placebo group.”

Amesh A. Adalja, MD, a senior scholar at the Johns Hopkins Center for Health Security, told Verywell that they were “not surprised” by the study’s findings because “the placebo effect is a strong and real phenomenon” and that “vaccines given by injection are a medical procedure and can have an impact, even when a placebo is being used.”

Russo added that the nocebo effect doesn’t just happen with COVID shots. “In any trial, there are side effects in the placebo group,” and “it’s how people react when they perceive that they receive something versus the true cause and effect of that something.”

Why the Nocebo Effect Happens

Doctors say that there are a few potential reasons why the nocebo effect happens. Richard Watkins, MD, an infectious disease physician and a professor of internal medicine at the Northeast Ohio Medical University, told Verywell that one is simply due to the expectations people have.

“People have been conditioned that, if they receive a shot, they are going to have some kind of adverse reaction,” said Russo, adding that other people are just nervous about needles and may have a reaction based on that fear.

“Some people have a perception that their body has been invaded,” said Russo. “As a result, they may develop symptoms that are independent of the vaccine.”

Experts stress that the study’s findings indicate that side effects from the COVID vaccine itself are not as common as many people think.

“This shows how the vaccines are much safer than many people perceive them to be,” said Watkins. “If you subtract out the perception of injection-related side effects versus side effects due to the vaccine itself, the actual number of side effects are much less,” Russo said.

Adalja urged people who are nervous about getting a COVID vaccine to consider that “overall, the COVID-19 vaccines are very safe and a lot of reactions people may experience may be unrelated to the vaccine’s contents.”

The information in this article is current as of the date listed, which means newer information may be available when you read this. For the most recent updates on COVID-19, visit our coronavirus news page.