Increased Serum MMP-9 in Long-COVID May Reect Activation of Microglia by SARS-CoV-2 Spike Protein

https://assets.researchsquare.com/files/rs-4151696/v1/3c8b49d7-acad-44ea-a2f0-0e0c76157e52.pdf?c=1711989805

Duraisamy Kempuraj, Irene Tsilioni, Kristina K. Aenlle, Nancy G. Klimas, Theoharis C. Theoharides (Tufts University School of Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University)

Abstract

Long-COVID is a major health concern because many patients develop chronic neuropsychiatric symptoms, but the precise pathogenesis is unknown. Matrix metalloproteinase-9 (MMP-9) can disrupt neuronal connectivity and was elevated in patients with COVID-19. MMP-9 was measured in the serum of long COVID patients and healthy controls, as well as in the supernatant fluid of cultured human SV-40 microglia, by commercial ELISA. Results were analyzed with one-way ANOVA. MMP-9 in the serum of Long-COVID patients and supernatant uid from cultured human microglia stimulated by recombinant SARS-CoV-2 Spike protein was assayed by ELISA. MMP-9 was significantly elevated in the serum of Long-COVID patients compared to healthy controls. Moreover, cultured human microglia released MMP-9 when stimulated by Spike protein.

In conclusion, MMP-9 may contribute to the development of Long-COVID and serve both as a prognostic biomarker and as target for treatment.

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