Most side effects noted in COVID vaccine trials may be due to 'nocebo effect'

More than a third of participants in COVID-19 vaccine clinical trials who received a placebo reported adverse events (AEs) such as headache and fatigue and contributed to the "nocebo effect," potentially rendering 76% of all AE reports after the first dose not true AEs, according to a meta-analysis yesterday in JAMA Network Open.Researchers from Beth Israel Deaconess Medical Center (BIDMC) in Boston and their US and German colleagues analyzed 12 articles published up to Jul 14, 2021, on randomized clinical vaccine trials involving 22,802 vaccine recipients and 22,578 placebo recipients.The nocebo effect happens when a trial participant develops side effects or symptoms simply because the person expects they'll occur after taking a drug or vaccine.

The authors of the meta-analysis used a ratio of reported AEs in the two groups to calculate the nocebo effect in COVID vaccine trials.Trials involving participants 16 years and older were included in the analysis if they evaluated AEs within 7 days of injection, included a placebo group, and provided separate AE reports for the vaccine and placebo groups.

The trials studied different types of COVID-19 vaccines (mRNA, viral vector, or protein-based) and were in different phases at the time of the study.Lower AE rates with placebo after 2 dosesSystemic AEs were reported by 35.2% of placebo recipients after the first dose, with headache (19.3%) and fatigue (16.7%) being the most common; after the second dose, 16.2% reported headache, and 14.9% cited fatigue.

In comparison, 46.3% of vaccine recipients reported at least one systemic AE after the first dose.After the second dose, systemic AEs were reported at lower rates in the placebo group (31.8%) but at higher rates in the