RT Journal Article
SR Electronic
T1 Targeting Neutrophils Extracellular Traps (NETs) reduces multiple organ injury in a COVID-19 mouse model
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2022.04.27.489676
DO 10.1101/2022.04.27.489676
A1 Flavio P. Veras
A1 Giovanni F. Gomes
A1 Bruna M. S. Silva
A1 Cicero J. L. R. Almeida
A1 Camila Meirelles S. Silva
A1 Ayda H. Schneider
A1 Emily S. Corneo
A1 Caio S. Bonilha
A1 Sabrina S. Batah
A1 Ronaldo Martins
A1 Eurico Arruda
A1 Alexandre T. Fabro
A1 José C. Alves-Filho
A1 Thiago M. Cunha
A1 Fernando Q. Cunha
YR 2022
UL http://biorxiv.org/content/early/2022/04/27/2022.04.27.489676.abstract
AB 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.