• Flavio Protasio Veras, Marjorie Cornejo Pontelli, Camila Meirelles Silva, Juliana E Toller-Kawahisa, Mikhael de Lima, Daniele Carvalho Nascimento, Ayda Henriques Schneider, Diego Caetité, Lucas Alves Tavares, Isadora M Paiva, Roberta Rosales, David Colón, Ronaldo Martins, Italo Araujo Castro, Glaucia M Almeida, Maria Isabel Fernandes Lopes, Maíra Nilson Benatti, Letícia Pastorelli Bonjorno, Marcela Cavichioli Giannini, Rodrigo Luppino-Assad, Sérgio Luna Almeida, Fernando Vilar, Rodrigo Santana, Valdes R Bollela, Maria Auxiliadora-Martins, Marcos Borges, Carlos Henrique Miranda, Antônio Pazin-Filho, Luis Lamberti P da Silva, Larissa Dias Cunha, Dario S Zamboni, Felipe Dal-Pizzol, Luiz O Leiria, Li Siyuan, Sabrina Batah, Alexandre Fabro, Thais Mauad, Marisa Dolhnikoff, Amaro Duarte-Neto, Paulo Saldiva, Thiago Mattar Cunha, José Carlos Alves-Filho, Eurico Arruda, Paulo Louzada-Junior, Renê Donizeti Oliveira, and Fernando Queiroz Cunha.
• Center of Research in Inflammatory Diseases, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.
• J. Exp. Med. 2020 Dec 7; 217 (12).

AbstractSevere 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.© 2020 Veras et al.

34 keywords...

hide…