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DUNEDIN, New Zealand: The COVID-19 pandemic has highlighted several interesting features of modern medical practice – most recently the “nocebo” response, which may account for a significant number of side effects people experience following vaccination.

Nocebo responses (from the Latin “noci”, which means to harm) are the opposite of the better-known placebo. While the latter describes improvements in symptoms following inert medication, the nocebo response heightens symptoms if a person anticipates them. It can increase pain if someone expects something will hurt.

A fascinating meta-analysis examined data from 12 clinical trials of COVID-19 vaccines, involving over 45,000 participants, and found that about two-thirds of common side effects people experience after vaccination could be due to a nocebo response, rather than the vaccine itself.


Nocebo responses can be troublesome and significant. They include headaches, fatigue, muscle pains, nausea or diarrhoea. Such symptoms may be related to anxiety or negative expectations, or day-to-day sensations being incorrectly attributed to treatment.

While previous analyses in other fields had already confirmed the presence of nocebo responses in randomised trials, COVID-19 vaccine research dramatically highlights its frequency.

The latest study found up to 35 per cent of patients in the placebo arm of vaccine trials had adverse events, such as headaches and fatigue. Mathematical analysis showed that 50 to 75 per cent of patient symptoms after the real vaccination (not placebo) may have been caused by those nocebo responses.