Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients

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 (Cas...

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Veröffentlicht in:	The Journal of experimental medicine Jg. 218; H. 3
Hauptverfasser:	Rodrigues, Tamara S, de Sá, Keyla S G, Ishimoto, Adriene Y, Becerra, Amanda, Oliveira, Samuel, Almeida, Leticia, Gonçalves, Augusto V, Perucello, Debora B, Andrade, Warrison A, Castro, Ricardo, Veras, Flavio P, Toller-Kawahisa, Juliana E, Nascimento, Daniele C, de Lima, Mikhael H F, Silva, Camila M S, Caetite, Diego B, Martins, Ronaldo B, Castro, Italo A, Pontelli, Marjorie C, de Barros, Fabio C, do Amaral, Natália B, Giannini, Marcela C, Bonjorno, Letícia P, Lopes, Maria Isabel F, Santana, Rodrigo C, Vilar, Fernando C, Auxiliadora-Martins, Maria, Luppino-Assad, Rodrigo, de Almeida, Sergio C L, de Oliveira, Fabiola R, Batah, Sabrina S, Siyuan, Li, Benatti, Maira N, Cunha, Thiago M, Alves-Filho, José C, Cunha, Fernando Q, Cunha, Larissa D, Frantz, Fabiani G, Kohlsdorf, Tiana, Fabro, Alexandre T, Arruda, Eurico, de Oliveira, Renê D R, Louzada-Junior, Paulo, Zamboni, Dario S
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	United States 01.03.2021
Schlagworte:	Apoptosis Comorbidity COVID-19 - pathology COVID-19 - virology Cytokines - biosynthesis Humans Inflammasomes - metabolism Lung - pathology Monocytes - metabolism NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Postmortem Changes SARS-CoV-2 - physiology Severity of Illness Index Treatment Outcome
ISSN:	1540-9538, 1540-9538
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Abstract	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.
AbstractList	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. 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.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.
Author	de Oliveira, Renê D R Ishimoto, Adriene Y Almeida, Leticia Castro, Italo A Becerra, Amanda Toller-Kawahisa, Juliana E de Lima, Mikhael H F de Sá, Keyla S G Luppino-Assad, Rodrigo Martins, Ronaldo B Lopes, Maria Isabel F Frantz, Fabiani G Andrade, Warrison A Gonçalves, Augusto V do Amaral, Natália B Vilar, Fernando C de Barros, Fabio C Cunha, Larissa D Giannini, Marcela C Alves-Filho, José C Rodrigues, Tamara S Silva, Camila M S Fabro, Alexandre T Cunha, Fernando Q Perucello, Debora B de Almeida, Sergio C L Siyuan, Li Benatti, Maira N Auxiliadora-Martins, Maria de Oliveira, Fabiola R Louzada-Junior, Paulo Veras, Flavio P Kohlsdorf, Tiana Pontelli, Marjorie C Bonjorno, Letícia P Caetite, Diego B Castro, Ricardo Nascimento, Daniele C Oliveira, Samuel Arruda, Eurico Batah, Sabrina S Santana, Rodrigo C Zamboni, Dario S Cunha, Thiago M
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Inflammatory Diseases, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil
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Snippet	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...
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SubjectTerms	Apoptosis Comorbidity COVID-19 - pathology COVID-19 - virology Cytokines - biosynthesis Humans Inflammasomes - metabolism Lung - pathology Monocytes - metabolism NLR Family, Pyrin Domain-Containing 3 Protein - metabolism Postmortem Changes SARS-CoV-2 - physiology Severity of Illness Index Treatment Outcome
Title	Inflammasomes are activated in response to SARS-CoV-2 infection and are associated with COVID-19 severity in patients
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