Targeting Neutrophils Extracellular Traps (NETs) reduces multiple organ injury in a COVID-19 mouse model

Veras, F. P.; Gomes, G. F.; Silva, B. M.; Almeida, C.; Silva, C. M.; Schneider, A. H.; Corneo, E. S.; Bonilha, C. S.; Batah, S. S.; Martins, R. P.; Arruda, E.; Fabro, A. T.; Alves-Filho, J. C. A.; Cunha, T. M.; Cunha, F. Q.

doi:10.1101/2022.04.27.489676

bioRxiv · 10.1101/2022.04.27.489676

Targeting Neutrophils Extracellular Traps (NETs) reduces multiple organ injury in a COVID-19 mouse model

Veras, F. P.·Gomes, G. F.·Silva, B. M.·Almeida, C.·Silva, C. M.·Schneider, A. H.·Corneo, E. S.·Bonilha, C. S.·Batah, S. S.·Martins, R. P.·Arruda, E.·Fabro, A. T.·Alves-Filho, J. C. A.·Cunha, T. M.·Cunha, F. Q.

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Abstract

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.

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Veras, F. P., Gomes, G. F., Silva, B. M., Almeida, C., Silva, C. M., Schneider, A. H., Corneo, E. S., Bonilha, C. S., Batah, S. S., Martins, R. P., Arruda, E., Fabro, A. T., Alves-Filho, J. C. A., Cunha, T. M., Cunha, F. Q.. 2022-04-27. Targeting Neutrophils Extracellular Traps (NETs) reduces multiple organ injury in a COVID-19 mouse model. https://doi.org/10.1101/2022.04.27.489676

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