TY - JOUR T1 - Targeting Neutrophils Extracellular Traps (NETs) reduces multiple organ injury in a COVID-19 mouse model JF - bioRxiv DO - 10.1101/2022.04.27.489676 SP - 2022.04.27.489676 AU - Flavio P. Veras AU - Giovanni F. Gomes AU - Bruna M. S. Silva AU - Cicero J. L. R. Almeida AU - Camila Meirelles S. Silva AU - Ayda H. Schneider AU - Emily S. Corneo AU - Caio S. Bonilha AU - Sabrina S. Batah AU - Ronaldo Martins AU - Eurico Arruda AU - Alexandre T. Fabro AU - José C. Alves-Filho AU - Thiago M. Cunha AU - Fernando Q. Cunha Y1 - 2022/01/01 UR - http://biorxiv.org/content/early/2022/04/27/2022.04.27.489676.abstract N2 - COVID-19 is characterized by severe acute lung injury, which is associated with neutrophils infiltration and release of neutrophil extracellular traps (NETs). COVID-19 treatment options are scarce. Previous work has shown an increase in NETs release in the lung and plasma of COVID-19 patients suggesting that drugs that prevent NETs formation or release could be potential therapeutic approaches for COVID-19 treatment. Here, we report the efficacy of NET-degrading DNase I treatment in a murine model of COVID-19. DNase I decreased detectable levels of NETs, improved clinical disease, and reduced lung, heart, and kidney injuries in SARS-CoV-2-infected K18-hACE2 mice. Furthermore, our findings indicate a potential deleterious role for NETs lung tissue in vivo and lung epithelial (A549) cells in vitro, which might explain part of the pathophysiology of severe COVID-19. This deleterious effect was diminished by the treatment with DNase I. Together, our results support the role of NETs in COVID-19 immunopathology and highlight NETs disruption pharmacological approaches as a potential strategy to ameliorate COVID-19 clinical outcomes.Competing Interest StatementThe authors have declared no competing interest. ER -