90 Chapter 4 access their exact vaccination date(s) and type(s) through the “Corona check” app/ website developed by the Dutch Ministry of Public Health, Welfare and Sport, ensuring accuracy. Despite the fact that regular care was given and treatment changes were made, we were still able to show an overall negative effect of COVID-19 vaccination. It is important to note that, although the effect size appears to be small, even subtle changes can have varying degrees of impact depending on the individual. Lastly, an additional limitation is the absence of validated questionnaires assessing disability, which might have offered a more comprehensive evaluation. Discrepancy in our findings for vaccination in comparison with COVID-infection may also be a result of higher peak antibody levels following vaccination compared to natural infection.33 However, it is important to note that individual antibody levels can vary depending on many factors, including the severity of infection. Interestingly, although COVID-19 infection did not lead to an increase in MMD, it did result in a higher number of MAMD. This could be a result of the increased use of pain medication to manage non-neurological or non-migrainous symptoms of COVID-19. Subgroup analysis indeed suggests that the increase in MAMD was driven solely by an increase in monthly analgesic days and not triptan days. Indeed, this increase in analgesic days was primarily observed on days with non-migrainous headache, indicating that the surge in analgesic intake is mainly associated with non-migrainous days. By contrast, after vaccination, both analgesic and triptan use increased in the first month, suggesting a stronger association with migraine. Moreover, the potential impact of analgesic use for non-headache purposes during the study period can be a possible explanation for the absence of an increase in MMD after COVID-19 infection. It is plausible that individuals resorted to analgesics to alleviate other COVID-19-related symptoms, which might have affected the occurrence of migraine attacks as a preventive measure. A principal strength of this study is the use of our validated E-headache diary. As a result of its time-locked design patients are prevented from changing or delaying their input, thereby evading recall bias.2 The automated algorithm ensures that every migraine day fulfilled necessary ICHD-3 criteria, consequently making the final results more reliable.3 Moreover, all patients completed their E-diaries as part of their routine care or for other research purposes. At the time of data collection, none of them were aware that these E-headache diary data might be used for analyzing the effect of COVID vaccination or infection. This approach helped to minimize the potential nocebo effect with vaccination and negative expectations of patients. Furthermore, our detailed E-headache diary tool ensured compliance in the post-infection month, and due to the validated algorithm ensures that assessment is not based on patients own interpretation of their headaches.
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