Abstract text (incl. figure legends and references)

Objective: To evaluate the clinical manifestations and the impact of (1) the infection caused by different SARS-CoV-2 variants and (2) different SARS-CoV-2 vaccines in patients with migraine.

Methods: Cross-sectional study of a cohort of patients with migraine, followed up in a Spanish Headache Unit. Through a digital questionnaire, we collected data on the characteristics of SARS-CoV-2 infection, clinical manifestations associated with vaccination against SARs-CoV-2, and their impact on migraine. We compared participants according to (1) SARs-CoV-2 variant (native strain, Alpha, Delta, Omicron) (2) type of vaccine (Pfizer, AstraZeneca, Moderna).

Results: 428 participants. COVID-19: 43.69% (187/428) had at least one infection. 83.42% (156/187) reported headache, being severe in 51.18% (81/187). The native strain and the Alpha variant were associated with a longer duration of headache compared to Delta and Omicron (15.17, 13.11, 9.16 and 6.84 days, respectively, p=0.0003). 9% (17/187) had a reinfection, all due to Omicron, and 75% (9/12) reported headache, less intense than the one of the first infection. In 28.20% (44/156) of patients their migraine got worse since COVID-19. Vaccination: 79.43% (340/428) were vaccinated, 51.47% (175/340) reported headache. There were no differences in the proportion of patients experiencing headache between different vaccines. More severe headache was observed with AstraZeneca (p=0.0041). 21.14% (37/175) of patients reported worsening of their migraine since the vaccination.

Conclusions: SARS-CoV-2 infection and vaccines are a frequent cause of headache in people with migraine, however reinfections (with or without previous vaccination), new variants and mRNA vaccines are associated with more benign forms. SARS-CoV-2 infection and vaccines are also factors responsible for migraine worsening.