Personalized serum proteome profiles of COVID-19-associated acute respiratory distress syndrome in response to mesenchymal stem cell therapy

Background: Mesenchymal stem cell (MSC) therapy is one of the therapeutic options for COVID-19-related acute respiratory distress syndrome (ARDS). However, not all patients benefit equally and the mechanism of action of the treatment remains unknown. Herein, we aimed to elucidate the molecular response to MSC treatment in COVID-19-related ARDS, and proposed protein signature to advocate for patient selection to maximize the benefit. Method: Five COVID-19-related ARDS patients who consented to compassionate placenta-derived (pc)-MSC treatment were followed for clinical response and disease progression. Serum samples were collected before and after pc-MSC infusion for quantitative proteomics analysis. Results: Following treatment, lung injury was significantly improved. Patients with invasive mechanical ventilation exhibited activation of inflammation, coagulation, and glucose metabolism, while it was inhibited in patients with high-flow oxygenation maintenance. Upregulations of complement system and HIF1α signaling may suggest a correlation to lung fibrosis. We proposed CD44, MMP2, MMP9, and CRP as a distinction panel to advise the response to pc-MSC treatment. Conclusion: We exploited molecular regulations in response to pc-MSC treatment for COVID-19-related ARDS and proposed protein signatures to assist treatment decisions. Large cohort study to observe the long-term impact should be implemented in the future.