BOSTON, Mass. (StudyFinds.org) – Could the majority of side-effects people feel after getting the COVID-19 vaccine all be in their heads? That’s what a new study claims, finding that more than half of the adverse effects patients experience are not from the actual vaccine, but a psychological reaction to it.

The psychological phenomenon called the “placebo effect” happens when people feel an improvement in their symptoms that is not directly related to their treatment or medication. Instead, the improvement comes from how the patient thinks they should feel following treatment. When people believe the treatment can cause harm, people may experience unpleasant side-effects, also known as the “nocebo effect.”

“Adverse events after placebo treatment are common in randomized controlled trials,” said lead author Julia W. Haas, PhD, an investigator in the Program in Placebo Studies at Beth Israel Deaconess Medical Center, in a media release. “Collecting systematic evidence regarding these nocebo responses in vaccine trials is important for COVID-19 vaccination worldwide, especially because concern about side effects is reported to be a reason for vaccine hesitancy.”

The researchers studied the data from 12 clinical trials testing the safety of COVID-19 vaccines. All trials had information on adverse events reported by 22,578 participants who received a placebo vaccine and 22,802 participants who received the actual COVID-19 vaccine.

1 in 3 not receiving the COVID vaccine still reported side-effects

After the first injection, more than 35% of participants in the placebo group reported systemic adverse events — reactions that affect the whole body — such as fever. One in five (19.6%) in the placebo group reported headaches, and 16.7% reported fatigue. Sixteen percent of the placebo group also experienced pain, redness, or swelling at the site of injection.

For comparison, 46% of actual vaccine recipients reported at least one systemic adverse event, and two-thirds had one local adverse event. Previous studies show that coronavirus vaccines can produce temporary side-effects ranging from mild aches to more severe conditions including blood clotting. In this trial, however, the team found a staggering 76% of the adverse effects reported by vaccinated patients were from the nocebo effect.

After the second dose, only 32% of the placebo group reported systemic side-effects, and 12% reported local side-effects. Conversely, the vaccine group continued to report more side-effects. More than six in 10 (61%) had systemic adverse events, and 73% continued to report local adverse events. The analysis revealed over half (52%) of the side-effects among vaccinated individuals came from the nocebo effect.

“Nonspecific symptoms like headache and fatigue – which we have shown to be particularly nocebo sensitive – are listed among the most common adverse reactions following COVID-19 vaccination in many information leaflets,” said senior author Ted Kaptchuk, director of the Program in Placebo Studies and the Therapeutic Encounter at BIDMC.

“Evidence suggests that this sort of information may cause people to misattribute common daily background sensations as arising from the vaccine or cause anxiety and worry that make people hyper alert to bodily feelings about adverse events.”

The findings appear in the journal JAMA Network Open.