81 Effect of COVID vaccination on monthly migraine days 4 INTRODUCTION The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a single stranded RNA virus and causes coronavirus disease 2019 (COVID-19). While initially perceived as a disease mainly affecting the respiratory system, it became apparent during the pandemic that COVID-19 has a broader effect, among which neurological manifestations including headache.1 The COVID-19 pandemic also had a major impact on the care of people who suffer from migraine. Consequently, telemedicine became an effective way to ascertain continuation of headache care for patients. The Leiden Headache Center was already using telemedicine before the outbreak of the COVID-19 pandemic, including the use of validated headache E-diaries.2, 3 E-diaries are a useful tool in migraine care and help to gain insight into attack frequency and treatment response.4, 5 As a result of the Leiden Headache Center’s prospective E-diary data collection during the COVID period as part of regular care, we have a unique opportunity to investigate the effects of COVID-19 infection and vaccination on an individual level in migraine patients. At this point, there are still limited data about the effect of a COVID-19 infection on primary headache disorders. Headache in the acute phase after COVID-19 infection seems to be more common in people with a previous history of headache disorders and often resembles the features of that headache disorder.6 Patients with a history of migraine self-reported to experience longer and more severe headaches attributed to COVID-19.7, 8 In The Netherlands, vaccination against COVID-19 started in January 2021, with four available vaccine types. The aim of vaccines is to deliver or produce antigens derived from the pathogen to trigger immune responses without causing considerable disease manifestations. The immune system recognizes the vaccine as foreign and mounts a response similar to that of an infection, but, because the pathogen is not able to multiply, the body is able to build immunity to the pathogen without causing the disease. Viral vector vaccines, such as Ad26.COV2.S (Janssen, Beerse, Belgium)9 and AZD1222 (AstraZeneca, Cambridge, UK)10, use viral DNA that is introduced into the target cells nucleus, where it is transcribed into mRNA. The mRNA strains introduced into the body will be translated and presented by the antigen-presenting cells (APC) to the Toll-like receptors (TLR), simulating a viral infection. Recognition by the TLR stimulates a T helper type 1 response by activating interferon (IFN)-1, which results in the engagement of several mediators such as cytokines and the complement system.11 This leads to a strong antibody production as well as a T-cell response, demonstrated by an increase in IFNγ, tumor necrosis factor (TNF)-α and interleukin (IL)-2.11, 12 The mRNA vaccines, such as BNT162b2 (Pfizer, New York, NY, USA/BioNTech, Mainz, Germany)13 and mRNA-1273 (Moderna, Cambridge, MA, USA)14, use a different
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