Comparison of Phenotypes of Headaches After COVID-19 Vaccinations Differentiated According to the Vaccine Used

<b>Background/Objectives</b>: In this ongoing, multicenter, global cohort observational study, phenotypes of headaches after COVID-19 vaccination were directly compared between different vaccines. <b>Methods</b>: Phenotypes of postvaccinal headache were recorded in 18,544 participants. The study was launched immediately after the start of the global COVID-19 vaccination campaign on 12 January 2021 and continued until 1 August 2023. Specific aspects of headaches and related variables were collected via an online questionnaire. The clinical headache characteristics of patients vaccinated with the Comirnaty (BioNTech), Jcovden (Johnson & Johnson), Sputnik V (Gamelaya), Covilo (Sinopharm), Spikevax (Moderna), Vaxzevria (AstraZeneca), and Convidecia (CanSino Biologics) vaccines were investigated. <b>Results</b>: Across all vaccines, the median and mean latency of headache onset after vaccine administration were 12 h and 23.3 h, respectively. The median and mean headache duration were 12 h and 23.3 h, respectively. When the nonreplicating viral vector vaccine Sputnik V was used, headaches occurred the fastest, with a latency of 17 h. The latencies for the Vaxzevria and Convidecia nonreplicating viral vector vaccines were 14.9 h and 19.1 h, respectively. The Covilo inactivated whole-virus vaccine had a latency of 20.5 h. The latencies of the mRNA-based Comirnaty and Spikevax vaccines were 26.0 h and 22.02 h, respectively. Analysis of variance revealed no significant differences in the mean duration of postvaccinal headache for the vaccines tested. Compared with the Comirnaty, Covilo, and Vaxzevria vaccines, the Spikevax vaccine induced significantly greater headache intensities. Vaxzevria was associated with a significantly higher frequency of concomitant symptoms than the other vaccines. <b>Conclusions</b>: The phenotype of postvaccinal headache can vary significantly between vaccines. These results have clinical implications for differentiating between postvaccinal headache and other primary and secondary headaches. This knowledge is clinically relevant in differentiating life-threatening vaccination complications, such as thrombotic syndromes, which are also associated with headaches. Based on these results, new diagnostic criteria for postvaccinal headaches can be developed.