New-Onset Headache After SARS-CoV-2 Infection and Vaccination: Results From Three Population-Based Cohorts in Norway.

BACKGROUND: Persistent headache after SARS-CoV-2 infections and vaccination has been reported. However, limited data exist on the risk of new-onset headache after these exposures compared to unexposed periods in the general population. METHODS: We used data from three population-based cohorts (N = 85,774, age 19-81 years). SARS-CoV-2 infections and vaccinations were obtained from national registries and questionnaires. Before and after Omicron emergence, participants stated whether they had been suffering from headache during the past year, reported headache characteristics, and time of onset. Time-dependent exposures were used to investigate the impact of SARS-CoV-2 infection and vaccination on the risk of new-onset headache. Headache subtypes were secondary outcomes. RESULTS: SARS-CoV-2 infection and first and second vaccine doses were associated with increased risk of new-onset headache. The three cohorts, representing different age groups, were analyzed separately. For pre-Omicron infections, the hazard ratio (HR) was 6.7 (95% confidence interval (CI) 4.8-9.2) and 6.5 (95% CI 3.8-11.1) among middle-aged women and men, respectively. For Omicron infection, HRs were 4.7 (95% CI 4.1-5.4) and 4.5 (95% CI 3.7-5.4), respectively. The risk increased with infection severity. Corresponding HRs for first and second vaccine doses, administered during low transmission, were 1.6 and 1.7, respectively, in women, and 1.5 for both doses in men. The third dose, given before the Omicron surge, was associated with 20%-40% protection against new-onset headache. CONCLUSIONS: SARS-CoV-2 infection was strongly associated with new-onset headache. Primary vaccination was associated with a small increased risk of headache during a low-transmission period, whereas booster vaccination offered protection during high-transmission.