Most COVID-19 Vaccine Side Effects Aren't Real, Caused By 'Nocebo Effect'

Up to 76% of all adverse effects attributed to COVID-19 vaccines during clinical trials were "nocebo responses," researchers discovered.

An analysis of 12 clinical trials on coronavirus vaccines totaling 45,380 participants — split into 22,578 placebo recipients and 22,802 real vaccine recipients — found that 76% of all systemic adverse effects, or effects that occurred away from the injection site, experienced by people following their first shots were caused by the "nocebo effect," according to a study published in the Jama Network Open medical journal Tuesday.

The nocebo effect is defined as a phenomenon in which a patient develops side effects or symptoms that can occur with a drug or other therapy just because the patient believes they may occur.

The placebo effect, in contrast, does the opposite and treats a condition with a fake treatment.

Around 24.3% of all the trials' reported local adverse effects — effects that were felt on the site of injection — were also attributed to the nocebo effect.

Following their second shots, the numbers for both systemic and local adverse effects that were nocebo responses dropped to 51.8% and 16.2%, respectively.

Headache and fatigue were the two most common adverse effects experienced by the placebo participants.

The research team, led by Dr. Julia W. Haas with the Beth Israel Deaconess Medical Center in Boston, Massachusetts, said the reported nocebo responses in the trials were potentially caused by "misattribution of routine background symptoms, anxiety and expectations of [adverse effects]."

Additionally, they explained that commonly experienced nonspecific symptoms such as headache or fatigue may have been tied to COVID-19 vaccines as adverse effects due to their inclusion in information leaflets.

"The current way of informing the public about potential vaccine [adverse effects] via leaflets and in the media may prompt or further increase nocebo responses," the study said.

Evidence suggested that adding simple but accurate information about nocebo responses helped reduce medication-related adverse effects in a clinical population, according to the researchers.

"Although more research on these communication strategies is needed, such honest information adds to full disclosure and is unlikely to cause harm," the team said.

"In addition, informing the public about the potential for nocebo responses may help reduce worries about COVID-19 vaccination, which might decrease vaccination hesitancy," they added.