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

• DOI: 10.1084/jem.20201129
• Publication Date: 2020-09-14T13:24:11Z
• Authors: Flavio Protasio V...; Marjorie Cornejo ...; Camila Meirelles ...; Juliana E. Toller...; Mikhael de Lima; Daniele Carvalho ...; Ayda Henriques Sc...; Diego Caetité; Lucas Alves Tavares; Isadora M. Paiva; Roberta Rosales; David Colón; Ronaldo Martins; Italo Araujo Castro; Glaucia M. Almeida; Maria Isabel Fern...; Maíra Nilson Benatti; Letícia Pastorell...; Marcela Cavichiol...; Rodrigo Luppino-A...; Sérgio Luna Almeida; Fernando Vilar; Rodrigo Santana; Valdes R. Bollela; Maria Auxiliadora...; Marcos Borges; Carlos Henrique M...; Antônio Pazin-Filho; Luis Lamberti P. ...; 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...; Eurico Arruda; Paulo Louzada-Junior; Renê Donizeti Oli...; Fernando Queiroz ...
• Keywords: Neutrophil Extracellular Traps; 2019-20 coronavirus outbreak; Betacoronavirus; Sars virus; Extracellular Vesicles

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