Hypotheses:

1. Severe new-onset headache after Covid-19 vaccine occur in a minor subset of vaccinated individuals.
2. Immunological reactivity with activation of trigeminal nociceptors can be among the mechanisms in severe headaches after Covid-19 vaccines.
3. Biomarkers in blood and CSF and imaging findings can be used to assess severe new-onset headache after Covid-19 vaccines.

The main aim of the project is to describe the characteristics of severe new-onset headache after Covid vaccine and the treatment effects.

Secondary aim:

1. Investigate potential mechanisms and analyse biomarkers to predict treatment effects.
2. To assess at baseline and 6-month follow-up the rate of brain MRI pathology.
3. To assess the change xof brain 18F-FDG PET metabolism from baseline and 6-month follow-up
4. To assess the levels of brain specific biomarkers
5. To assess the level of blood specific biomarkers

Duration of Study participation:

• Enrollment: 24 months
• Follow-up: at 3 and 6 months after inclusion. For those with continued severe headache regular 3-month controls are planned during the study.

Total study duration 24 months

Study Design: Prospective observational multi-center study

Cohort study of patients with new-onset severe headache after Covid-19 vaccine. Patients referred to the participating headache clinics for severe headache after Covid vaccine will be invited to participate in the study. The invitation will be given in conjunction with their visit to the headache specialist. Patients already diagnosed and treated for severe headache after Covid vaccine will be invited to participate during control visits at the participating centres. After written informed consent information information from the initial phases will be collected retrospectively from the medical records of the patients that have already been diagnosed and started with treatment. Further information will be collected prospectively. For newly diagnosed patients all information will be collected prospectively. Blood samples will be drawn to assess immunological mechanisms.

Inclusion criteria:

• Patients aged ≥ 18 years with new onset severe headache or severe worsening of pre-existing headache within one week after Covid vaccination and has not resolved within 3 weeks.
• Inclusion within 12 months after symptom onset.
• Informed written consent signed by the patient.

Exclusion criteria:

• Patients not available for follow-up assessments (e.g. non-resident).

IInclusion criteria:

• Patients aged ≥ 18 years with new onset severe headache or severe worsening of pre-existing headache within one week after Covid vaccination and has not resolved within 3 weeks.
• Inclusion within 12 months after symptom onset.
• Informed written consent signed by the patient.

Exclusion criteria:

• Patients not available for follow-up assessments (e.g. non-resident).

Cohort study of patients with new-onset severe headache after Covid-19 vaccine. Patients referred to the participating headache clinics for severe headache after Covid vaccine will be invited to participate in the study. The invitation will be given in conjunction with their visit to the headache specialist. Patients already diagnosed and treated for severe headache after Covid vaccine will be invited to participate during control visits at the participating centres. After written informed consent information information from the initial phases will be collected retrospectively from the medical records of the patients that have already been diagnosed and started with treatment. Further information will be collected prospectively. For newly diagnosed patients all information will be collected prospectively. Blood samples will be drawn to assess immunological mechanisms