Well-Being Prevention & Cures

New study suggests most COVID-19 vaccine side effects can be attributed to ‘nocebo effect’

Story at a glance

  • In a study published in the journal JAMA Network Open, researchers from the Beth Israel Deaconess Medical Center (BIDMC) conducted a meta-analysis of 12 clinical trials of COVID-19 vaccines.
  • Researchers estimated that 76 percent of all headaches, fatigue and other systemic adverse events reported after the first COVID-19 vaccine dose and 52 percent after the second can be attributed to the nocebo effect.
  • The study’s authors said the findings should be considered in public vaccination programs and could help reduce concerns about COVID-19 vaccination and decrease vaccine hesitancy.

A new study suggests most of the mild symptoms associated with the COVID-19 vaccine may be caused by a negative version of the placebo effect, or “nocebo effect,” rather than from the actual vaccine itself.  

The nocebo effect occurs when a person ingests a substance with no medical effects, such as a sugar pill or syringe full of saline, but experiences negative symptoms associated with treatment because they expect to.  

In a study published in the journal JAMA Network Open, researchers from the Beth Israel Deaconess Medical Center (BIDMC) conducted a meta-analysis of 12 clinical trials of COVID-19 vaccines that included adverse effect reports from 22,578 placebo recipients and 22,802 vaccine recipients to compare the two groups.  

Among the vaccinated group, researchers found 46 percent of participants experienced “systemic adverse events,” such as headache, fever and fatigue, following the first dose, while two-thirds reported “local effects,” such as pain at the injection site, redness or swelling. Following the second dose, 61 percent reported systemic adverse events and nearly two-thirds “local effects.”  

While more symptoms were reported among the vaccine group, about 35 percent of participants given the placebo claimed to experience symptoms like headache and fever after the first jab while 16 percent experienced local symptoms. After the second dose, symptoms among the placebo dropped to 32 percent.  


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After establishing a baseline for nocebo cases, researchers estimated that 76 percent of all headaches, fatigue and other systemic adverse events reported after the first COVID-19 vaccine dose and 52 percent after the second can be attributed to 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,” Ted J. Kaptchuk, a researcher at BIDMC and professor of medicine at Harvard Medical School, said in a statement 

“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,” Kaptchuk said.  

Researchers said the findings should be considered in public vaccination programs and could help reduce concerns about COVID-19 vaccination and decrease vaccine hesitancy.  


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