The fibrin-derived peptide FX06 protects human pulmonary endothelial cells against the COVID-19-triggered cytokine storm.

Introduction: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been a major health emergency since its emergence in late 2019. Endothelial dysfunction is a hallmark of COVID-19, leading to severe illness, i.e. coagulopathy, multi-organ failure. FX06, a fibrin-derived peptide naturally occurring in the human body, formerly known as Bβ Methods: To mimic the inflammatory status of COVID-19, a human pulmonary microvascular endothelial cell line (ECs) - HULEC-5a, was treated with a cytokine cocktail comprised of ten different cytokines or chemokines at concentrations found in serum profiles of COVID-19 patients with severe illness, further referred to as the severe cytokine cocktail. ECs were treated with the severe cytokine cocktail for 24 h, in the absence or presence of FX06 for 2 h. Results: The severe cytokine cocktail enhanced peripheral blood mononuclear cell (PBMC)-endothelial adhesion and monolayer transmigration. This deleterious effect was significantly reduced by FX06. FX06 was also shown to mitigate the cytotoxic activity of allogeneic CD8 Conclusion: Overall, FX06 shows promising potential in normalizing ECs and reducing vascular leakage to protect the endothelium against the proinflammatory effect of COVID-19-triggered cytokines.