Potential association of cluster headache with certain COVID-19 vaccines: An assessment from the pharmacovigilance databases.

OBJECTIVES/

BACKGROUND

The main objective of our study was to assess the potential association between coronavirus disease 2019 (COVID-19) vaccination and cluster headache (CH) using a pharmacovigilance approach. A secondary objective was to determine whether COVID-19 vaccines predominantly triggered onset or worsening of the disease. Recent pharmacovigilance studies and case reports have suggested an association between COVID-19 vaccines and cluster headache. In order to evaluate whether COVID-19 vaccines could possibly elicit the onset of cluster headache or be responsible for worsening of the disease, we conducted a retrospective case-non-case pharmacovigilance study using the international VigiBase pharmacovigilance database and analyzed the reported cases of cluster headache in the Base Nationale de Pharmacovigilance, French National Pharmacovigilance Database (BNPV).

METHODS

VigiBase was queried up to February 23, 2025, for all reports related to cluster headache and COVID-19 vaccines. To evaluate the potential association, we performed a disproportionality analysis. This analysis relied on the calculation of the information component, for which a 95% confidence interval lower-bound positivity was required for signal detection. The narratives of the reported cases of cluster headache in the BNPV were analyzed to determine whether COVID-19 vaccination was responsible for the onset or worsening of the disease.

RESULTS

When focusing on the different COVID-19 vaccines, Vaxzevria was found to be the strongest signal (IC025: 3.05). Lower signals were observed for the other COVID-19 vaccines, including Comirnaty (IC025: 1.62), Spikevax (IC025: 1.24), and Jcovden (IC025: 0.05). The analysis of the 55 CH cases reported in the BNPV revealed a slight predominance of onset (24/55 cases classified as CH) over worsening of the disease (17/55 cases classified as CH).

CONCLUSIONS

Our study supports the possibility of a potential association between COVID-19 vaccines and cluster headache through an updated pharmacovigilance analysis. The signal appears to be more pronounced with the Vaxzevria vaccine.