For those who suffered side effects following COVID vaccination, the adverse symptoms were likely well worth it — even if they didn’t really have to experience them.
According to the US Centers for Disease Control and Prevention, some 77% of those who received a vaccine dose from Pfizer, Moderna or Johnson & Johnson reported at least one non-local symptom soon after the jab, such as headache, fever, fatigue and muscle pain.
But a new study published in the journal JAMA Network Open on Tuesday has revealed that nearly two-thirds of those symptoms were likely self-induced via what researchers are calling the “nocebo” effect.
Scientists at Beth Israel Deaconess Medical Center in Boston found that many volunteers in vaccine control groups — those who unknowingly received an inert, placebo vaccine — claimed to have suffered the same flu-like symptoms as their vaccinated cohorts.
“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.
“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,” Kaptchuk added.
Researchers found that both vaccine and placebo recipients reported ill effects at similar rates — 22,802 and 22,578 reports, respectively — per data collected from 12 recent vaccine trials.
More than 35% of placebo recipients experienced at least one systemic symptom, meaning those not associated with the injection site. Headache was the most common, with 19.6% reporting, followed by fatigue at 16.7%. By comparison, 46% of real vaccine recipients said they’d felt at least one systemic symptom.
Meanwhile, 16% of placebo recipients also reported local effects, such as pain, itchiness and swelling at the site of injection after the first dose, whereas around 66% of truly vaccinated volunteers experienced the same local effects.
The numbers reveal that at least some of the side effects — an estimated two-thirds — reported by individuals who received an active vaccine treatment can be attributed to the nocebo effect, since many of the same symptoms occurred in the placebo group, according to researchers.
As participants progressed to additional doses, the number of those who reported adverse symptoms following a second placebo jab fell to 32%, and local site discomfort down to 12%.
But for the bona fide vaccine group, their reporting of systemic reaction shot up to 61%, and injection site effects sprang to 73%. Researchers believe this may be the outcome of participants anticipating symptoms for their second dose, prompting a psychosomatic response that matched their expectations.
The study then further suggests that the nocebo effect could be responsible for up to half of all reported side effects following the second dose, for those who receive two-dose therapies, such as those from Pfizer and Moderna.
Researchers acknowledged the limitations in that the 12 trials they included in the study took different approaches to reporting symptoms and employed various vaccine types — mRNS, protein-based and viral-vector-based.
Kaptchuk said he hoped their study “could help reduce worries about COVID-19 vaccination, which might decrease vaccination hesitancy.”