Two thirds of side effects associated with the Covid-19 vaccine are likely to be caused by the “nocebo effect” – where people become ill because they expect to, scientists believe.

US researchers at Beth Israel Deaconess Medical Centre (BIDMC) in Boston, studied the rates of adverse events reported by 22,000 vaccine trial participants who received a real jab, compared with a similar number who received a dummy injection.

After one dose, more than 35 per cent of placebo participants experienced symptoms such as headaches, fever and swelling at the injection site, compared with 46 per cent of the vaccine group.

After a second dose, 32 per cent given a placebo reported side effects compared with 61 per cent who had a real jab.

Analysis suggested that the nocebo effect accounted for 76 per cent of side effects after a first dose, and 52 per cent after a second, meaning that overall, around two thirds of symptoms were imagined.

Experts said that people should be warned they could experience nocebo symptoms in order to lessen fears.

‘Hyper alert to bodily feelings’

“Nonspecific symptoms like headache and fatigue 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 and professor of medicine at Harvard Medical School.  

“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.

“Medicine is based on trust. Our findings lead us to suggest that informing the public about the potential for nocebo responses could help reduce worries about Covid-19 vaccination, which might decrease vaccination hesitancy.”

‘Vaccine hesitancy’ 

The placebo effect is the phenomenon where a person’s physical or mental health improves after they receive a treatment with no pharmacological therapeutic benefit, such as a sugar pill or a syringe full of saline.

But sometimes placebo effects can also harm – the so-called nocebo effect occurs when a person experiences unpleasant side effects after a dummy treatment.

“Adverse events after placebo treatment are common in randomised controlled trials,” said lead author Dr Julia Haas, an investigator in the Program in Placebo Studies at BIDMC.

“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 research was published in the journal Jama Network Open.