Reproducible cluster headache remission following SARS-CoV-2 mRNA vaccination: a case report

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.