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Patterns of Past COVID-19 and EBV Infection in Primary Headache Disorders: A Population Study

Keshet Pardo1,2, Maor Mermelstein1,2, Shlomit Yust-Kats1,2

  • 1Neurology Department, Rabin Medical Center, Petach Tikva, Israel.

Brain and Behavior
|September 26, 2025
PubMed

Insights

Epstein-Barr virus (EBV) infection is linked to migraine, while COVID-19 is associated with tension-type headaches (TTH), particularly in those with anxiety or depression. These findings highlight distinct viral impacts on primary headache disorders.

Area of Science:

  • Neurology
  • Infectious Diseases
  • Epidemiology

Background:

  • Viral infections are recognized triggers for chronic headaches.
  • Post-COVID-19 pandemic, numerous patients reported persistent headaches, yet the impact on primary headache disorders remains unclear.
  • This study investigates the relationship between prior viral infections and newly diagnosed primary headache disorders.

Purpose of the Study:

  • To determine if patients with newly diagnosed primary headache disorders have higher rates of prior COVID-19 and Epstein-Barr virus (EBV) infections.
  • To explore the differential impact of viral infections on specific primary headache disorders.

Main Methods:

  • A case-control study was conducted using data from Clalit Health Services.
  • The study compared patients diagnosed with primary headache disorders (migraine, tension-type headache, cluster headache) between June 2020 and June 2023 with non-headache controls.
  • Rates of prior COVID-19 and EBV infections were analyzed.

Main Results:

  • Epstein-Barr virus (EBV) infection showed an association with both migraine and tension-type headache (TTH).
  • In multivariable analysis, only the association between EBV and migraine remained significant.
  • COVID-19 infection was associated with migraine but lost significance when adjusted for comorbidities.
  • COVID-19 showed a significant association with TTH among patients with anxiety or depression.
  • Cluster headache showed no significant differences compared to controls.

Conclusions:

  • Epstein-Barr virus (EBV) infection is primarily associated with migraine.
  • COVID-19 infection is primarily associated with tension-type headache (TTH), especially in individuals with anxiety or depression.
  • These findings suggest distinct pathophysiological mechanisms and differential immune system involvement in primary headache disorders.
Abstract

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