The Nocebo Effect in SARS-CoV-2 Vaccination

The Nocebo Effect in SARS-CoV-2 Vaccination

The nocebo effect refers to a negative reaction expressing itself as adverse symptoms which are mostly driven by the expectation of an individual that a negative effect will follow the administration of a medicinal dietary intervention, such as a vaccine, drug, or food item. A potentially easier way of describing this phenomenon is to think of it as a self-fulfilling prophecy in which the belief of the occurrence of a future event contributes to the actual occurrence of that event. The nocebo effect is common, yet underappreciated phenomenon in medical practice and has been identified in a variety of clinical trials in many different fields, such as allergology or the treatment of gastrointestinal disorders.

“This data makes evident that a significant number of adverse events are not attributable to the vaccine but may rather be attributable to the nocebo effect.”

Various studies have investigated the occurrence of the nocebo phenomenon in medical trials assessing the safety of SARS-CoV-2 vaccines, a politically charged topic. One large systematic review examined the adverse effects reported by a total of three SARS-CoV-2 vaccine trials, two of which were mRNA-based, and one being adenovirus-based. In the sum total of 45,000 study subjects the most reported adverse effects to administration of either the vaccine or the placebo were fatigue, headache, muscle aches and pains, and injection site reactions. Specifically, fatigue was reported in 21-29% of patients who received the placebo, compared to 38-42% of patients administered the actual vaccine. Headaches occurred in 24-27% of placebo participants in contrast to 33-39% of the subjects receiving the vaccine. Muscle pain was reported by 10-14% of the placebo group and in 18-33% of the active treatment group. Importantly, injection site reactions differed most between the groups, with 12-17% of adverse effects in the injection site reported by the placebo group, and 48-84% reported by the vaccine subjects. This data makes evident that a significant number of adverse events, specifically subjective symptoms such as fatigue, headaches, and muscle pain, are not attributable to the vaccine but may rather be attributable to the nocebo effect.

“…associated with an increasing rejection of science in general and an increasing popularity of pseudoscientific myths.”

The importance of the study and other studies of this kind lies in the fact that they promote enhanced awareness about the safety of the SARS-CoV-2 vaccination. This is particularly crucial because a significant amount of the general population still refuses to be vaccinated against COVID-19, based on unjustified fears about the safety and efficacy of the injection. However, this hesitancy is also influenced strongly by political and cultural factors and often conspiracy theories about the government and the pharmaceutical industry.

Unfortunately, these belief systems associated with an increasing rejection of science in general and an increasing popularity of pseudoscientific myths. The stronger these negative beliefs about the vaccine become, the more likely a nocebo response will occur. Most people refusing to get vaccinated are poorly informed about the safety of the vaccine, the importance of community immunity, and the vaccine’s effectiveness in protecting against severe COVID-19 illness. Large-scale studies investigating phenomena such as the nocebo effect are thus crucial in learning more and educating the general population about the safety of the SARS-CoV-2 vaccine.

With converging evidence from several different clinical trials suggesting that a significant proportion of the reported adverse symptoms attributed to vaccine administration are due to the nocebo effect, the safety and efficacy of the COVID-19 vaccine may be even higher than originally reported and believed to be.


Jill Horn is a recent UCLA graduate with a Neuroscience. She is deeply interested in the interconnectedness of body, mind, and spirit takes an integrative approach to health and well-being.