Background: Delayed-onset of headache seems a specific feature of cerebrovascular events (CVE) after COVID-19 vaccines.
Methods: All consecutive events reported to the United States Vaccine Adverse Reporting System following COVID-19 vaccines (January 1-June 24, 2021), were assessed. The timing of headache onset post-vaccination in subjects with and without concomitant CVE, including cerebral venous thrombosis (CVT), ischemic stroke (IS), and intracranial haemorrhage (ICH) was analysed. The diagnostic accuracy in predicting concurrent CVE of the guideline-proposed threshold of 3 days from vaccination to headache onset was evaluated.
Results: There were 314,610 events following 306,907,697 COVID-19 vaccine doses, including 41,700 headaches, and 178/41,700 (0.4%) CVE. The median time between the vaccination and the headache onset was shorter in isolated headache (1 day vs. 4 (CVT), 3 (IS), or 10 (ICH) days, all P<0.001). Delayed onset of headache had an area under the curve of 0.83 (95% confidence interval (CI): 0.75-0.97) for CVT, 0.70 (95% CI: 0.63-76) for IS and 0.76 (95% CI: 0.67- 84) for ICH, and >99% negative predictive value.
Conclusion: Headache following COVID-19 vaccination occurs within 1 day and is rarely associated with CVE. Delayed onset of headache ≥3 days post-vaccination was an accurate diagnostic biomarker for the occurrence of a concomitant CVE.