Publication date: Jun 24, 2025

Adverse events (AE) of varying severity commonly occur after vaccinations, potentially related to the nocebo effect. The randomized single-center clinical trial “LIFe Study” at the Vaccination Center Lichtenfels, Germany, investigates AE based on doctor-patient interaction and administered vaccine type following COVID-19 vaccination. Vaccinees receiving first or second doses were randomized: the control group (n=1,006) received in-depth medical briefings elaborating all possible AE; the experimental group (n=937) concise medical briefings comprising only medically relevant facts to the. Nocebo effects were quantified by self-reported AE frequency and severity; then AE across vaccine types and vaccinee demographics were compared including vaccinees receiving third (booster) doses. Questionnaires allowed rating 12 listed AE from absent, mild, moderate, to severe (valued as {0,1,2,3}, respectively), and summed to yield a score ranging from 0 to 36. Most AE were mild with no significant difference in mean AE (mAE) score between control (3. 95, σ = 4. 70) and experimental groups (3. 96, σ = 4. 75), nor in the number of participants reporting drug use for symptom relief (n = 208, n = 192; p = 0. 54), or sick leave (n = 82, n = 82; p = 0. 32). Higher mAE were associated with follow-up doses of Spikevax compared to Comirnaty, young age (r = -0. 15, 95% CI [-0. 19; -0. 11], p = 9cD710), and female gender (mAE 5. 00, σ = 5. 32 vs male 3. 05, σ = 3. 93). These findings suggest that the nocebo effect was not a significant factor in COVID-19 vaccinations and allow optimization of future vaccination strategies.

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