Lessons from the coronavirus disease 2019 pandemic : investigating the bidirectional relationship between coronavirus disease 2019 and migraine based on the MECH-HK cohort study

Abstract

Background: Although the coronavirus disease 2019 (COVID-19) pandemic has ended, its impact on patients with migraine has revealed critical gaps in understanding how migraine interacts with respiratory infections. Exploring this bidirectional relationship is essential for improving migraine management and protecting vulnerable populations during future outbreaks. Objectives: To examine (1) the impact of migraine on COVID-19 manifestations and the risk of post-acute sequelae of COVID-19 (PASC), and (2) the effect of COVID-19 infection on migraine features. Methods: We conducted a longitudinal study, with both prospective and retrospective data collection, nested within the Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK) cohort. Two cohort-wide assessments were conducted at baseline (2019–2020) and follow-up (2021–2023). Monthly migraine features, including attack frequency, duration, and intensity, were prospectively tracked using migraine diaries. COVID-19-related outcomes, including symptom burden, self-perceived severity, time-to-test negativity, and PASC, were retrospectively self-reported during follow-up. To examine the bidirectional relationship, Substudy 1 used regression models to evaluate how baseline migraine status influenced infection-related outcomes among participants who contracted COVID-19 between baseline and follow-up. Substudy 2 used mixed-effects models to compare longitudinal changes in migraine features between the infection and noninfection groups. Results: In Substudy 1 (n = 1085; mean age: 54.3 ± 9.4 years), women with migraine (n = 122) reported significantly greater COVID-19 symptom burden compared to participants without migraine (mild: adjusted rate ratio [aRR], 1.30; 95% confidence interval [CI], 1.16–1.47; moderate/severe: aRR, 1.44; 95% CI, 1.03–2.01), higher self-perceived severity (adjusted odds ratio [aOR], 1.45; 95% CI, 1.01–2.09), and an elevated risk of PASC (aOR, 1.87; 95% CI, 1.23–2.82), which may suggest heightened vulnerability in this population. In Substudy 2, participants who contracted COVID-19 (n = 73) exhibited a 35% increase in the geometric mean of monthly migraine attack frequency during the first 3 months postinfection (adjusted geometric mean ratio [aGMR], 1.35; 95% CI, 1.10–1.65), whereas no such increase was observed in the noninfection group (n = 128) during the corresponding period. No significant changes in attack duration or intensity were observed in either group. Conclusions: Migraine and COVID-19 exhibit a bidirectional relationship. Women with migraine experienced more severe COVID-19 manifestations and greater PASC risk, whereas infection was associated with increased migraine attack frequency. These findings emphasize the need for tailored migraine management strategies, particularly in the context of future viral outbreaks.