Impact of the medical briefing and vaccine type on adverse events following COVID-19 vaccination: A randomized clinical trial

Abstract

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_control = 208, n_experimental = 192; p = 0.54), or sick leave (n_control = 82, n_experimental = 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 = 9×10^-12), 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.