Reproducible cluster headache remission following SARS-CoV-2 mRNA vaccination: a case report
Abstract
Cluster headache (CH) is among the most severe primary pain disorders and can be highly refractory to conventional treatment. Although SARS-CoV-2 infection and mRNA vaccination have been predominantly linked to the exacerbation or new onset of CH, we here report the case of a 26-year-old male with a seven-year history of refractory chronic CH (cCH) who experienced a rapid and sustained complete remission (CR) following SARS-CoV-2 mRNA booster vaccination. This remission, documented by daily pain intensity ratings on a numerical rating scale (NRS, 0–10) derived from a prospectively maintained headache diary, was characterized by an abrupt cessation of high-intensity nocturnal attacks immediately following vaccination. After sustained remission of the previous chronic nightly attack pattern, the patient subsequently developed recurrent CH activity; a subsequent JN.1-adapted mRNA vaccination was again followed by rapid remission. The repeated close temporal association between vaccination and remission is notable, although spontaneous disease fluctuation cannot be excluded in a single-patient observation. To characterize the immunological environment accompanying clinical remission, we performed longitudinal multiparametric immunophenotyping of peripheral blood at three time points surrounding the 2025 vaccination event. We observed a transient expansion of natural killer (NK) cells and monocytes, upregulation of the checkpoint marker PD-1 on CD4+ T cells, and expansion of myeloid-derived suppressor cells (MDSCs), observed in temporal association with the onset of CR. Antigen-specific stimulation assays revealed a concurrent induction of IFN-γ and TNF-α producing CD4+ T cells, consistent with a TH1-polarized immune response. To our knowledge, this is the first report of a reproducible, vaccination-induced CR in chronic CH, supported by high-resolution clinical and immunological longitudinal data. The findings suggest that targeted immune activation may be capable of resetting pathological neuro-immune circuits in refractory headache disorders and warrant prospective investigation.
Related
- Decreasing the Risk of Lead Migration in Occipital Nerve Stimulation for Cluster Headache Using Dedicated Leads
- Visual outcomes and headache in intracranial hypertension following cerebral venous sinus thrombosis: A retrospective cohort study
- Harmine Plus Exendin-4 Enhances Remission of Recent-Onset Type 1 Diabetes Following Anti-CD3 Therapy
- Post-Vaccination Chemosensory Dysfunction: Changes Following SARS-CoV-2 Vaccination in a Global Study.
- Small Quantity Lipid-Based Nutritional Supplementation and Measles Vaccination Coverage in Children Aged 6-23\,Months: A Pragmatic Cluster-Randomized Trial
BibTeX
@article{gottlich2026reproducible,
title = {{Reproducible cluster headache remission following SARS-CoV-2 mRNA vaccination: a case report}},
author = {Simon Göttlich and Jernej Pusnik and Emmanuil Osypchuk and Hendrik Streeck and Stefanie Andrea Erika Held and Anne-Katrin Pröbstel and Peter Brossart and Christian R. Klein},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1969032},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1969032},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Reproducible cluster headache remission following SARS-CoV-2 mRNA vaccination: a case report
AU - Simon Göttlich
AU - Jernej Pusnik
AU - Emmanuil Osypchuk
AU - Hendrik Streeck
AU - Stefanie Andrea Erika Held
AU - Anne-Katrin Pröbstel
AU - Peter Brossart
AU - Christian R. Klein
PY - 2026
DA - 2026/11/05
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1969032
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1969032
AB - Cluster headache (CH) is among the most severe primary pain disorders and can be highly refractory to conventional treatment. Although SARS-CoV-2 infection and mRNA vaccination have been predominantly linked to the exacerbation or new onset of CH, we here report the case of a 26-year-old male with a seven-year history of refractory chronic CH (cCH) who experienced a rapid and sustained complete remission (CR) following SARS-CoV-2 mRNA booster vaccination. This remission, documented by daily pain intensity ratings on a numerical rating scale (NRS, 0–10) derived from a prospectively maintained headache diary, was characterized by an abrupt cessation of high-intensity nocturnal attacks immediately following vaccination. After sustained remission of the previous chronic nightly attack pattern, the patient subsequently developed recurrent CH activity; a subsequent JN.1-adapted mRNA vaccination was again followed by rapid remission. The repeated close temporal association between vaccination and remission is notable, although spontaneous disease fluctuation cannot be excluded in a single-patient observation. To characterize the immunological environment accompanying clinical remission, we performed longitudinal multiparametric immunophenotyping of peripheral blood at three time points surrounding the 2025 vaccination event. We observed a transient expansion of natural killer (NK) cells and monocytes, upregulation of the checkpoint marker PD-1 on CD4+ T cells, and expansion of myeloid-derived suppressor cells (MDSCs), observed in temporal association with the onset of CR. Antigen-specific stimulation assays revealed a concurrent induction of IFN-γ and TNF-α producing CD4+ T cells, consistent with a TH1-polarized immune response. To our knowledge, this is the first report of a reproducible, vaccination-induced CR in chronic CH, supported by high-resolution clinical and immunological longitudinal data. The findings suggest that targeted immune activation may be capable of resetting pathological neuro-immune circuits in refractory headache disorders and warrant prospective investigation.
SN - 1664-3224
ER -