Work

From past to present and toward the future: a mechanism-informed clinical framework for COVID-19-associated headache and post-viral pain

Year: 2026

Type: review

Abstract: Headache is a prominent acute and persistent neurological manifestation of COVID-19, representing both as a significant clinical challenge and a valuable model for understanding the neurotropic effects of SARS-CoV-2. This review synthesizes evidence showing that the epidemiology of COVID-19 headache is distinctly shaped by younger age, female sex, and a prior history of headache disorders; its clinical phenotypes are diverse, strongly associating with chemosensory dysfunctions such as anosmia; and its core pathophysiology involves neuroinflammation (e.g., cytokine-mediated pathways), trigeminovascular activation, and sex-specific neuroendocrine-immune interactions. Although acute headache often responds to conventional analgesics, persistent cases-a major component of Post-Acute Sequelae of COVID-19 (PASC)-necessitate a multidisciplinary management approach. This contrasts with the typically self-limiting headache following vaccination. Future research should prioritize longitudinal studies to define chronicity, mechanistic investigations into sex-specific pathways, and the development of phenotype-specific, personalized therapeutic strategies.

Source: Frontiers in Neurology

DOI: 10.3389/fneur.2026.1937278