Calcitonin Gene-Related Peptide Monoclonal Antibody Treatment in Nine Cases of Persistent Headache Following COVID-19-Infection

Abstract

Background: The coronavirus disease 2019 (COVID-19) pandemic has underscored the need for effective treatment for post-infectious complications, including headaches. Owing to the variable nature of post-COVID headaches, identifying effective therapies through clinical trials is challenging and the burden on patients is often severe. This study aimed to summarize the presentation of post-COVID headache in clinical practice and evaluate its response to treatment with calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs). Methods: In this retrospective cohort study, medical records obtained between March 2022 and May 2024 from two centers were analyzed. The study included nine patients with new-onset or significantly worsening or altered patterns of previous headaches lasting more than one month after COVID-19 infection who subsequently received CGRP mAbs. Demographics, headache frequency and severity, medication use, and quality of life were assessed before and after CGRP mAb treatment. Results: All patients were female (median age, 48 years), and 88.9% had headaches for more than three months despite conventional preventive therapies. Headache Impact Test-6 (HIT-6) scores were greater than 60 in all patients, and the headaches were unilateral (66.7%) and pulsating (22.2%). After CGRP mAb treatment, the monthly headache days, headache severity scores, and monthly medication days decreased significantly (median with interquartile range: 25 [15–28] to 5 [4–10], P = 0.012; 8 [7–9] to 3 [2–4], P = 0.011; 16 [15–20] to 5 [4–10], P = 0.017). The HIT-6 (65 [60–68] to 48 [48–60], P = 0.017) and Patient Health Questionnaire-9 scores (14 [5–15] to 10 [4–12], P = 0.028) also decreased significantly after treatment. Conclusion: CGRP mAbs may be considered a potential treatment option for persistent headaches following COVID-19, especially the long-COVID headaches. Their use may contribute to an improved burden of headache and quality of life and may help alleviate the psychological symptoms associated with persistent headaches. © 2025 Elsevier B.V., All rights reserved.