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Long COVID elevated MMP-9 and release from microglia by SARS-CoV-2 Spike protein

Duraisamy Kempuraj1, Irene Tsilioni2, Kristina K Aenlle1,3

  • 1Institute for Neuro-Immune Medicine (INIM), Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Ft. Lauderdale, FL, 33328, United States of America.

Translational Neuroscience
|October 15, 2024
PubMed
Abstract

Insights

Matrix metalloproteinase-9 (MMP-9) is elevated in Long COVID patients and contributes to neuropsychiatric symptoms. Flavonoids like luteolin show potential in inhibiting MMP-9 release, offering a therapeutic target for Long COVID treatment.

Area of Science:

  • Neuroscience
  • Immunology
  • Virology

Background:

  • Long COVID presents significant challenges due to chronic neuropsychiatric symptoms with unknown causes.
  • Matrix metalloproteinase-9 (MMP-9) is implicated in disrupting neuronal connectivity and is found at higher levels in Long COVID patients.

Purpose of the Study:

  • To investigate the role of MMP-9 in Long COVID pathogenesis.
  • To determine if SARS-CoV-2 Spike protein stimulates MMP-9 release from microglia.
  • To evaluate the inhibitory effects of specific flavonoids on MMP-9 release.

Main Methods:

  • MMP-9 levels were quantified in serum from Long COVID patients and healthy controls using enzyme-linked immunosorbent assay (ELISA).
  • Human microglia cell lines were stimulated with SARS-CoV-2 Spike protein, lipopolysaccharide (LPS), or neurotensin (NT).
  • The effect of luteolin and methlut pretreatment on Spike protein-induced MMP-9 release was assessed.

Main Results:

  • Serum MMP-9 levels were significantly higher in Long COVID patients compared to controls.
  • Microglia cell lines released significant amounts of MMP-9 when stimulated by LPS, NT, or Spike protein.
  • Luteolin and methlut pretreatment markedly inhibited Spike protein-induced MMP-9 release.

Conclusions:

  • Elevated MMP-9 from Spike protein-stimulated microglia may contribute to Long COVID neuropsychiatric symptoms.
  • MMP-9 presents a potential therapeutic target for Long COVID.
  • Flavonoids, such as luteolin, demonstrate potential as treatments for Long COVID by inhibiting MMP-9 release.
Keywords:
MMP-9brain inflammationlong COVIDluteolinmast cellsmicroglia

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