Podoplanin and CLEC-2 levels in patients with COVID-19

Background: Podoplanin (PDPN gene) and CLEC-2 are involved in inflammatory hemostasis and have also been related with the pathogenesis of thrombosis. Emerging evidence also suggests that podoplanin can exert protective effects in sepsis and acute lung injury. In the lungs, podoplanin is coexpressed with angiotensin-converting enzyme 2, which is the main entry receptor for SARS-CoV-2.Objectives: To explore the role of podoplanin and CLEC-2 in COVID-19.Methods: Circulating levels of podoplanin and CLEC-2 were measured in 30 consecutive patients with COVID-19 admitted due to hypoxia and in 30 age-and sex-matched healthy individuals. Podoplanin expression in lungs from patients who died of COVID19 was obtained from 2 independent public databases of single-cell RNA sequencing, from which data from control lungs were also available.Results: Circulating podoplanin levels were lower in patients with COVID-19, whereas no difference was observed in CLEC-2 levels. Podoplanin levels were significantly inversely correlated with markers of coagulation, fibrinolysis, and innate immunity. Single-cell RNA sequencing data confirmed that PDPN is coexpressed with angiotensinconverting enzyme 2 in pneumocytes and showed that PDPN expression is lower in this cell compartment in the lungs of patients with COVID-19.Conclusion: Circulating levels of podoplanin are lower in patients with COVID-19, and the magnitude of this reduction is correlated with hemostasis activation. We also demonstrate the downregulation of PDPN at the transcription level in pneumocytes. Together, our exploratory study questions whether an acquired podoplanin deficiency could be involved in the pathogenesis of acute lung injury in COVID-19 and warrants additional studies to confirm and refine these findings.