1. Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients
- Author
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Eurico Arruda, Thiago M. Cunha, Letícia Pastorelli Bonjorno, Dario S. Zamboni, Sérgio C. L. Almeida, Maria Auxiliadora-Martins, Maira N. Benatti, Tiana Kohlsdorf, Debora B. Perucello, Flávio P. Veras, Adriene Y. Ishimoto, Amanda Becerra, Alexandre Todorovic Fabro, Italo A. Castro, Diego B. Caetite, Rodrigo de Carvalho Santana, Sabrina Setembre Batah, Ricardo M. C. Castro, Fernando Crivelenti Vilar, Juliana E Toller-Kawahisa, Rodrigo Luppino-Assad, Letícia Yamawaka de Almeida, Larissa D. Cunha, Marjorie Cornejo Pontelli, Natalia B. do Amaral, Renê Donizeti Ribeiro de Oliveira, Warrison A. Andrade, José C. Alves-Filho, Tamara S Rodrigues, Fernando Q. Cunha, Li Siyuan, Maria Isabel Fernandes Lopes, Ronaldo B. Martins, Marcela C Giannini, Daniele C. Nascimento, Mikhael Haruo Fernandes de Lima, Camila Meirelles de Souza Silva, Fabiola Reis de Oliveira, Fabiani Gai Frantz, Keyla Santos Guedes de Sá, Augusto V. Gonçalves, Fábio Cury de Barros, Samuel L. Oliveira, and Paulo Louzada-Junior
- Subjects
0301 basic medicine ,Inflammasomes ,Innate Immunity and Inflammation ,Immunology ,Apoptosis ,INFLAMAÇÃO ,Autopsy ,Inflammation ,Comorbidity ,Disease ,Severity of Illness Index ,Peripheral blood mononuclear cell ,Monocytes ,Infectious Disease and Host Defense ,03 medical and health sciences ,0302 clinical medicine ,NLR Family, Pyrin Domain-Containing 3 Protein ,Severity of illness ,medicine ,Humans ,Immunology and Allergy ,Lung ,SARS-CoV-2 ,business.industry ,Brief Definitive Report ,COVID-19 ,Inflammasome ,Pathophysiology ,Treatment Outcome ,030104 developmental biology ,Postmortem Changes ,030220 oncology & carcinogenesis ,Cytokines ,medicine.symptom ,business ,medicine.drug - Abstract
This work shows that inflammasomes are activated in response to SARS-CoV-2 infection in vitro and in COVID-19 patients. Activation of inflammasomes in moderate and severe cases of COVID-19 contributes to the exacerbated inflammatory response, impacting disease progression and clinical outcome., Severe cases of COVID-19 are characterized by a strong inflammatory process that may ultimately lead to organ failure and patient death. The NLRP3 inflammasome is a molecular platform that promotes inflammation via cleavage and activation of key inflammatory molecules including active caspase-1 (Casp1p20), IL-1β, and IL-18. Although participation of the inflammasome in COVID-19 has been highly speculated, the inflammasome activation and participation in the outcome of the disease are unknown. Here we demonstrate that the NLRP3 inflammasome is activated in response to SARS-CoV-2 infection and is active in COVID-19 patients. Studying moderate and severe COVID-19 patients, we found active NLRP3 inflammasome in PBMCs and tissues of postmortem patients upon autopsy. Inflammasome-derived products such as Casp1p20 and IL-18 in the sera correlated with the markers of COVID-19 severity, including IL-6 and LDH. Moreover, higher levels of IL-18 and Casp1p20 are associated with disease severity and poor clinical outcome. Our results suggest that inflammasomes participate in the pathophysiology of the disease, indicating that these platforms might be a marker of disease severity and a potential therapeutic target for COVID-19., Graphical Abstract
- Published
- 2020
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