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

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 fluid 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.