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

Ivanio Teixeira Borba-Junior; Franciele Lima; Davi Sidarta Vitoria Rodrigues Oliveira; Carla Roberta Peachazepi Moraes; Joyce M Annichino-Bizzacchi; Bruna Bombassaro; André C Palma; Fabio Trindade Maranhao Costa; Maria Luiza Moretti; Eli Mansour; Licio Augusto Velloso; Fernanda Andrade Orsi; Erich Vinicius De Paula

doi:10.1016/j.rpth.2023.100282

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

Res Pract Thromb Haemost. 2023 Jun 21;7(5):100282. doi: 10.1016/j.rpth.2023.100282. Online ahead of print.

Authors

Ivanio Teixeira Borba-Junior¹, Franciele Lima¹, Davi Sidarta Vitoria Rodrigues Oliveira¹, Carla Roberta Peachazepi Moraes¹, Joyce M Annichino-Bizzacchi^{1

2}, Bruna Bombassaro¹, André C Palma¹, Fabio Trindade Maranhao Costa³, Maria Luiza Moretti¹, Eli Mansour¹, Licio Augusto Velloso^{1

4}, Fernanda Andrade Orsi^{1

2}, Erich Vinicius De Paula^{1

2}

Affiliations

¹ State University of Campinas, Faculty of Medical Sciences, Campinas, Brazil.
² State University of Campinas, Hematology and Hemotherapy Center, Campinas, Brazil.
³ State University of Campinas, Institute of Biology, Campinas, Brazil.
⁴ State University of Campinas, Obesity and comorbidities Center.

Abstract

Introduction: Podoplanin (PDPN gene) and CLEC-2 are involved in inflammatory hemostasis and have also been related with the pathogenesis of thrombosis. Emerging evidence also suggest that podoplanin can exert protective effects in sepsis and in acute lung injury. In lungs, podoplanin is co-expressed with ACE2, which is the main entry receptor for SARS-CoV-2.

Aim: 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 COVID-19 patients admitted due to hypoxia, and in 30 age- and sex-matched healthy individuals. Podoplanin expression in lungs from patients who died of COVID-19 was obtained from two independent public databases of single-cell RNAseq from which data from control lungs were also available.

Results: Circulating podoplanin levels were lower in COVID-19, while no difference was observed in CLEC-2 levels. Podoplanin levels were significantly inversely correlated with markers of coagulation, fibrinolysis and innate immunity. scRNAseq data confirmed that PDPN is co-expressed with ACE2 in pneumocytes, and showed that PDPN expression is lower in this cell compartment in lungs from patients with COVID-19.

Conclusion: Circulating levels of podoplanin are lower in 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 warrant additional studies to confirm and refine these findings.

Keywords: Acute lung injury; CLEC-2; COVID-19; Podoplanin; scRNAseq.