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MCAS

Prevalence and treatment response of neuropsychiatric disorders in mast cell activation syndrome

Weinstock LB, Afrin LB, Reiersen AM, Brook J, Blitshteyn S, Ehrlich G, Schofield JR, Kinsella L, Kaufman D, Dempsey T, Molderings GJ. Prevalence and treatment response of neuropsychiatric disorders in mast cell activation syndrome. Brain, Behavior, & Immunity – Health. 2025;48:101048.doi:10.1016/j.bbih.2025.101048

  • MCAS is a common inflammatory disease characterized by mast cell dysregulation.
  • 19 neurologic and 14 psychologic disorders were significantly increased in MCAS subjects.
  • Chemical mediators, genetic predisposition, and life experiences could determine which disorders occur or worsen.
Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19

Fekete, R., Simats, A., Bíró, E., Pósfai, B., Cserép, C., Schwarcz, A., Szabadits, E., Környei, Z., Tóth, K., Fichó, E., Szalma, J., Vida, S., Kellermayer, A., Dávid, C., Acsády, L., Kontra, L., Silvestre-Roig, C., Moldvay, J., … Dénes, Á. (2025). Microglia dysfunction, neurovascular inflammation and focal neuropathologies are linked to IL-1- and IL-6-related systemic inflammation in COVID-19. Nature Neuroscience, 28(3), 558–576. DOI: 10.1038/s41593-025-01871-z

  • Neuropathological findings show microglial dysfunction, astrocyte activation, and neurovascular inflammation, driven by systemic immune signaling (IL-1, IL-6), even without direct viral invasion.
  • Evidence of blood–brain barrier disruption and gliovascular pathology, supporting ongoing brain inflammation.
  • Findings suggest self-sustaining inflammatory loops between the immune system and the brain, contributing to persistent symptoms.
  • Clinical observations show improvement with H1/H2 antihistamines, supporting a role for mast cell activation in symptom persistence.
  • Overall, the research points toward immune dysregulation, rather than viral persistence, as a key driver in a subset of Long COVID cases.
Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Options

Slama Schwok A, et al. Long Neuro-COVID-19: Current Mechanistic Views and Therapeutic Options. Biomolecules. 2024;14(9):1081. doi:10.3390/biom14091081.

  • Comprehensive review of proposed mechanisms underlying neurological Long COVID.

  • Describes neuroimmune activation, endothelial dysfunction, blood–brain barrier disruption, and microglial priming.

  • Emphasizes that neurological symptoms can persist without detectable viral RNA in the CNS.

  • Supports reframing Long COVID brain symptoms as a disorder of immune and vascular regulation.

Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation

Salvucci F, Codella R, Coppola A, et al. Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation. Front Cardiovasc Med. 2023;10:1202696. doi:10.3389/fcvm.2023.1202696.

Mast cell activation in Long COVID (related work)

  • Observational study evaluating Long COVID patients treated with H1/H2 antihistamines.

  • Reports improvement in fatigue, cognitive symptoms, tachycardia, and other systemic complaints.

  • Supports the hypothesis that mast cell activation contributes to Long COVID symptom persistence.

  • Suggests immune dysregulation—rather than viral persistence—may drive ongoing symptoms in a subset of patients.