Sars-Cov-2 spike protein and plasma from covid-19 patients induce extracellular traps by myeloid-derived suppressor cells

Germana Grassi¹Simona Gili¹Rita Casetti¹Zulema Antonia Percario²Nicola Tumino³Paola Vacca³Stefania Notari¹Veronica Bordoni³Eleonora Cimini¹Flavia Cristofanelli¹Dorotea Rubino¹Francesca Nonini¹Elisabetta Affabris²Luisa Marchioni¹Chiara Agrati³Alessandra Sacchi^2*

• ¹National Institute for Infectious Diseases Lazzaro Spallanzani (IRCCS), Rome, Lazio, Italy
• ²University of Rome "Roma Tre", Rome, Italy
• ³Bambino Gesù Children's Hospital (IRCCS), Rome, Lazio, Italy

Polymorphonuclear-myeloid-derived suppressor cells (PMN-MDSC) are elevated in COVID-19 patients, playing a crucial role in suppressing the SARS-CoV-2 specific T-cell response and serving as an early marker for disease progression. In this study, we investigated the involvement of PMN-MDSC from COVID-19 patients in the formation of extracellular traps (ET).We found that platelet-rich plasma (PRP) from COVID-19 patients, unlike that from healthy donors, induced ET formation by PMN-MDSC. However, platelets were not the primary drivers of ET release, implying the presence of other contributing factors. Furthermore, the PRP-induced ET was found to be independent of Toll-like receptor 4 (TLR4) signaling.Interestingly, the SARS-CoV-2 Spike protein itself can trigger ET formation via a TLR4-dependent pathway. Additionally, PMN-MDSC induced endothelial cell apoptosis through an ET-independent mechanism.These findings highlight a previously unrecognized contribution of PMN-MDSCs to the thrombotic complicationThese findings highlight the potential role of PMN-MDSC in contributing to the thrombotic complications observed in severe COVID-19 cases, underscoring their detrimental impact on disease progression.