Allergy-like nocebo events reported with COVID-19 vaccines: a case control study

Allergy-like symptoms after COVID-19 vaccination are frequently reported, though true allergic reactions are rare. Clinical trials suggest many reported symptoms may reflect nocebo effects. This study aimed to characterize nocebo responses and identify associated factors.

A case-control study was conducted using pharmacovigilance records and a cross-sectional questionnaire. Cases were defined as patients reporting allergy-like symptoms without anaphylaxis; controls reported reactogenicity or localized reactions. Data on demographics, medical history, vaccinations, and psychological factors were analyzed using multivariate logistic regression to identify risk factors associated with nocebo effects.

Among 1038 participants, 320 were nocebo cases and 718 were controls. Cases frequently reported cutaneous (71.8%) and respiratory (38.8%) symptoms, with 43.4% occurring after the first dose. Nocebo responses were positively associated with a history of allergy (OR 1.78, 95% CI: 1.32-2.4) and COMIRNATY vaccine (OR 1.60, 95% CI: 1.20-2.14), and negatively correlated with perceived vaccine effectiveness (OR 0.93, 95% CI: 0.88-0.98).

The nocebo effect appears to differ by vaccine type and is more common in individuals with a history of allergy and lower perceived vaccine effectiveness. While further research is needed to validate these findings, this underscores the importance of clear, evidence-based communication to reduce nocebo responses.