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19th Jan 2022

Nearly two-thirds of covid jab side effects could be placebo, study finds

Charlie Herbert

Headaches and fatigue were the most common ‘nocebo’ side effects

A new study has found that nearly two-thirds of reported side effects to the covid vaccine could be due to a negative version of the placebo effect.

In trials that involved some participants being given the vaccine and others being given a placebo injection of inactive salt solution, researchers compared the rates of adverse events reported by those who received the vaccines to the rate of side effects experienced by those who received the placebo injection.

The study, published in JAMA Network Open on Tuesday, found that while a significant number of those who received the vaccine reported side effects, nearly a third of trial participants who got the placebo also reported at least one adverse effect.

The placebo effect usually works by seeing a person’s health improve when they are given a treatment with no pharmacological therapeutic benefit in the belief that it is a medical treatment.

However in this case, the opposite occurred, with individuals who received the placebo experiencing unpleasant side effects. This is known as the ‘nocebo’ effect.

In the 12 trials, adverse effects were reported by 22,578 placebo recipients and 22,802 vaccine recipients.

Researchers calculated that about two-thirds of common side effects reported in covid vaccine trials are driven by the ‘nocebo’ effect, due to factors such as anxiety and expectation as opposed to the constituents of the vaccine.

The researchers describe how after the first injection more than 35 per cent of those in the placebo groups experienced so-called “systemic” side-effects, such as headache and fatigue, with 16 per cent reporting site-specific ailments including arm pain or redness or swelling at the injection site.

The most common side effects reported by placebo recipients were headaches (19.6 per cent) and fatigue (16.7 per cent).

Those who received the vaccine did report more side effects though, with 46 per cent of vaccine recipients experienced at least one systemic adverse event and two-thirds experiencing local side effects such as arm pain.

However researchers believe that at least some of the reported side effects from those who received the vaccine can be put down to the ‘nocebo’ effect because many of the same effects were reported by the placebo group.

“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,” the study’s senior author Ted J Kaptchuk, professor of medicine at Harvard Medical School, said in a statement.

He added: “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 study also found that after a second dose of the placebo jab, adverse events among the placebo group dipped to 32 per cent reporting any systemic events, and 12 per cent reporting any local effects.

In contrast, those who received two doses of the real vaccine were much more likely to report side effects after the second jab, with 61 per cent reporting systemic adverse events and 73 per cent reporting local adverse events.

Researchers estimated that the ‘nocebo’ effect could account for nearly half of the side effects reported after the second dose.

A reason for the increase in side effects reported after the second dose of vaccine was not confirmed in the study but researchers suspected it may be because participants anticipated more adverse effects for their second jab.

Dr Kaptchuk concluded that by informing people of the ‘nocebo’ effect, the findings could be useful in helping to “reduce worries about Covid-19 vaccination, which might decrease vaccination hesitancy.”

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