Assessment of Myeloperoxidase in Lung Injury Among Elderly COVID-19 Patients Using a Murine Model

MANUSCCOVID-19 disproportionately affects elderly populations, with lung injury being a significant cause of morbidity and mortality. The pronounced fatality rate is largely attributed to the development of acute respiratory distress syndrome, conventionally believed to be primarily driven by a cytokine storm. However, drugs targeting cytokine storms have demonstrated limited therapeutic benefits. This study investigates Myeloperoxidase (MPO) as a biomarker for lung injury in elderly COVID-19 patients. Analyzing hospitalized patients, we observed higher MPO levels in older individuals compared to younger counterparts. Utilizing a murine model, we demonstrated that older mice exhibit increased MPO protein in bronchoalveolar lavage fluid, despite a weaker cytokine storm. The role of MPO in lung injury was further elucidated by employing MPO-deficient mice, which showed reduced neutrophil infiltration and lung damage. A high-throughput screen identified Oxyresveratrol as a potent MPO inhibitor. In our COVID-19 mouse model, Oxyresveratrol treatment significantly reduced inflammatory markers and lung injury. These findings suggest MPO as a viable biomarker for severe COVID-19 in elderly patients and highlight Oxyresveratrol as a potential therapeutic agent for MPO-induced lung damage.