If the placebo effect describes the benefits felt by a patient who has been given an inactive substance, the nocebo effect describes the harmful effects.

Researchers from Harvard University-affiliated Beth Israel Deaconess Medical Center studied data generated from placebo-controlled clinical studies of COVID-19 vaccines.

While they found significantly more side effects in participants who received a vaccine, about a third of subjects who received a placebo also complained of side effects, with fatigue and headache being at the top of the list.

The meta-analysis looked at 12 studies in which nearly 45,000 people were split equally between a vaccine and a placebo.

After the first injection, more than 35% of subjects receiving placebo experienced a systemic side effect, and 16% experienced a localized side effect. By comparison, 46% of participants who received the vaccine reported a systemic side effect, and two-thirds (67%) reported a localized side effect.

Because many of these effects also occurred in the placebo group, the authors concluded that 76% of side effects in the vaccination group were due to the nocebo effect.

After the second dose, the placebo group reported fewer side effects than the first (32% systemic and 12% localized), but the vaccination group reported more (61% systemic and 73% localized).

Researchers attribute 52% of the side effects experienced after the second injection to the nocebo effect. They speculate that this may be a combined effect of an increased immune response and the fact that vaccinated people expect a greater effect after their second dose.

Researchers believe that some people mistakenly attribute normal day-to-day problems to the vaccine, because they have been made fully aware of the potential side effects of vaccination. They say these warnings can cause stress and anxiety, and make people more susceptible to the slightest sensation.

The authors acknowledge that their analysis includes a relatively small number of studies with different perspectives, and therefore caution should be exercised in interpreting the results.

Yet the researchers believe that informing the population of this noso effect would be beneficial because it could counteract some’s reluctance to vaccinate, according to them.

The findings of this study have been published by the medical journal jama network openOpinion (new window)Opinion,