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SARS-CoV-2–triggered neutrophil extracellular traps mediate COVID-19 pathology

2020; Rockefeller University Press; Volume: 217; Issue: 12 Linguagem: Inglês

10.1084/jem.20201129

1540-9538

Flávio P. Veras, Marjorie Cornejo Pontelli, Camila M. Silva, Juliana E. Toller-Kawahisa, Mikhael de Lima, Daniele C. Nascimento, Ayda Henriques Schneider, Diego B. Caetité, Lucas Tavares, Isadora Marques Paiva, Roberta Costa, David F. Colón, Ronaldo B. Martins, Ítalo A. Castro, Glaucia M. Almeida, Maria Isabel Fernandes Lopes, Maíra Nilson Benatti, Letícia Pastorelli Bonjorno, Marcela C Giannini, Rodrigo Luppino Assad, Sérgio C. L. Almeida, Fernando Crivelenti Vilar, Rodrigo de Carvalho Santana, Valdes Roberto Bóllela, Maria Auxiliadora‐Martins, Marcos de Carvalho Borges, Carlos Henrique Miranda, Antônio Pazin‐Filho, Luis Lamberti P. da Silva, Larissa D. Cunha, Dario S. Zamboni, Felipe Dal‐Pizzol, Luiz O. Leiria, Li Siyuan, Sabrina Setembre Batah, Alexandre Todorovic Fabro, Thaís Mauad, Marisa Dolhnikoff, Amaro Nunes Duarte‐Neto, Paulo Hilário Nascimento Saldiva, Thiago M. Cunha, José C. Alves‐Filho, Eurico Arruda, Paulo Louzada‐Júnior, Renê Donizeti Ribeiro de Oliveira, Fernando Q. Cunha,

Inflammation biomarkers and pathways

Severe COVID-19 patients develop acute respiratory distress syndrome that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that neutrophil extracellular traps (NETs) have been described as important mediators of tissue damage in inflammatory diseases, we investigated whether NETs would be involved in COVID-19 pathophysiology. A cohort of 32 hospitalized patients with a confirmed diagnosis of COVID-19 and healthy controls were enrolled. The concentration of NETs was augmented in plasma, tracheal aspirate, and lung autopsies tissues from COVID-19 patients, and their neutrophils released higher levels of NETs. Notably, we found that viable SARS-CoV-2 can directly induce the release of NETs by healthy neutrophils. Mechanistically, NETs triggered by SARS-CoV-2 depend on angiotensin-converting enzyme 2, serine protease, virus replication, and PAD-4. Finally, NETs released by SARS-CoV-2-activated neutrophils promote lung epithelial cell death in vitro. These results unravel a possible detrimental role of NETs in the pathophysiology of COVID-19. Therefore, the inhibition of NETs represents a potential therapeutic target for COVID-19.